WO2024209270A2 - Méthodes et compositions pour le traitement du cancer à l'aide de polypeptides recombinants - Google Patents
Méthodes et compositions pour le traitement du cancer à l'aide de polypeptides recombinants Download PDFInfo
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Definitions
- Esophageal cancer is one of the most lethal cancers in the world, currently ranking sixth among cancers in mortality.
- Esophageal cancer including esophageal squamous cell carcinoma and esophageal adenocarcinoma, involves the abnormal proliferation of esophageal epithelial cells.
- Radiotherapy, surgical resection, and chemotherapy are the primary clinical treatments for esophageal cancer. Outcomes are suboptimal with only 20% of patients surviving at least 5 years following diagnosis. The survival rate of patients treated solely with chemotherapy is still low, and there is a significant need for novel, targeted therapies that demonstrate long-lasting effects.
- compositions to treat cancer in a subject e.g., human subject using a composition comprising an epitope, e.g., T cell epitope, e.g., cancer specific CD8+ T cell epitope.
- an epitope e.g., T cell epitope, e.g., cancer specific CD8+ T cell epitope.
- the present disclosure provides a method of treating cancer in a subject in need thereof comprising administering to the subject a composition comprising: (i) a recombinant polypeptide comprising a cancer-specific CD8+ T cell epitope; (ii) a polynucleotide encoding a recombinant polypeptide comprising a cancer-specific CD8+ T cell epitope; (iii) a vector comprising (i) or (ii); (iv) antigen presenting cells (APCs) comprising (i), (ii), or (iii); or (v) T cells stimulated with APCs comprising (i) or (ii); wherein: the subject expresses an MHC encoded by an HLA-A*03:01 allele and the cancer-specific CD8+ T cell epitope is LKPDHIQR, KTEVHGRLK, RVSLPKLGYK, or SLFGARPGR; the subject expresses an MHC encoded by
- the present disclosure provides a method of treating cancer in a subject in need thereof comprising administering to the subject a composition comprising: (i) a recombinant polypeptide comprising a cancer-specific CD8+ T cell epitope; (ii) a polynucleotide encoding a recombinant polypeptide comprising a cancer-specific CD8+ T cell epitope; (iii) a vector comprising (i) or (ii); (iv) antigen presenting cells (APCs) comprising (i), (ii), or (iii); or (v) T cells stimulated with APCs comprising (i) or (ii); wherein: the subject expresses an MHC encoded by an HLA-A*02:01 allele and the cancer-specific CD8+ T cell epitope is GVYDGREHTV or KLVELEHTL; the subject expresses an MHC encoded by an HLA-B*07:02 allele and the cancer
- the present disclosure provides a method of treating cancer in a subject in need thereof comprising administering to the subject a composition comprising: (i) a recombinant polypeptide comprising a cancer-specific CD8+ T cell epitope; (ii) a polynucleotide encoding a recombinant polypeptide comprising a cancer-specific CD8+ T cell epitope; (iii) a vector comprising (i) or (ii); (iv) antigen presenting cells (APCs) comprising (i), (ii), or (iii); or (v) T cells stimulated with APCs comprising (i) or (ii); wherein: the subject expresses an MHC encoded by an HLA-A*03:01 allele and the cancer-specific CD8+ T cell epitope is SLYQTIRLK, KTPLHTLLK, RLHSFTLRQK or RVFTSSLKTK; the subject expresses an MHC encoded by
- the present disclosure provides a method of treating cancer in a subject in need thereof comprising administering to the subject a composition comprising: (i) a recombinant polypeptide comprising a cancer-specific CD8+ T cell epitope; (ii) a polynucleotide encoding a recombinant polypeptide comprising a cancer-specific CD8+ T cell epitope; (iii) a vector comprising (i) or (ii); (iv) antigen presenting cells (APCs) comprising (i), (ii), or (iii); or (v) T cells stimulated with APCs comprising (i) or (ii); wherein: the subject expresses an MHC encoded by an HLA-A*02:01 allele and the cancer-specific CD8+ T cell epitope is GVYDGREHTV or KLVELEHTL; the subject expresses an MHC encoded by an HLA-A*03:01 allele and the cancer
- the present disclosure provides a method of treating cancer in a subject in need thereof comprising administering to the subject a composition comprising: (i) a recombinant polypeptide comprising a cancer-specific CD8+ T cell epitope; (ii) a polynucleotide encoding a recombinant polypeptide comprising a cancer-specific CD8+ T cell epitope; (iii) a vector comprising (i) or (ii); (iv) antigen presenting cells (APCs) comprising (i), (ii), or (iii); or (v) T cells stimulated with APCs comprising (i) or (ii); wherein: the subject expresses an MHC encoded by an HLA-A*15:01 allele and the cancer-specific CD8+ T cell epitope is GQHLHLETF; the subject expresses an MHC encoded by an HLA-C*03:04 allele and the cancer-specific CD8+ T cell
- the present disclosure provides method of treating cancer in a subject in need thereof, the method comprising administering to the subject a composition comprising (i) a recombinant polypeptide comprising a cancer-specific CD8+ T cell epitope, or (ii) a polynucleotide encoding a recombinant polypeptide comprising a cancer-specific CD8+ T cell epitopes, (iii) a vector comprising (i) or (ii), (iv) antigen presenting cells (APCs) comprising (i),
- T cells stimulated with APCs comprising (i), (ii), or (iii).
- the subject expresses an MHC encoded by an HLA- A*03:01 allele and the cancer-specific CD8+ T cell epitope is LKPDHIQR, KTEVHGRLK, RVSLPKLGYK, or SLFGARPGR.
- the subject expresses an MHC encoded by an HLA-B*07:02 allele and the cancer-specific CD8+ T cell epitope is NLRPPTQEL.
- the subject expresses an MHC encoded by an HLA-A*31 :01 allele and the cancer-specific CD8+ T cell epitope is SLFGARPGR.
- the subject expresses an MHC encoded by an HLA-B*07:02 allele and the cancer-specific CD8+ T cell epitope is LRPPTQEL.
- the subject expresses an MHC encoded by an HLA-A*02:01 allele and the cancer-specific CD8+ T cell epitope is GVYDGREHTV or KLVELEHTL.
- the subject expresses an MHC encoded by an HLA-B*07:02 allele and the cancer-specific CD8+ T cell epitope is SPSSASLAL or KPRPDVTNEL.
- the subject expresses an MHC encoded by an HLA-B*35:03 allele and the cancer-specific CD8+ T cell epitope is PSSASLAL, RPASPRPAP, NLRPPTQEL, or KPRPDVTNEL.
- the subject expresses an MHC encoded by an HLA-B*35:03 allele and the cancer-specific CD8+ T cell epitope is SPSSASLAL or KPRPDVTNEL.
- the subject expresses an MHC encoded by an HLA-B*40:01 allele and the cancer-specific CD8+ T cell epitope is KEFAFLEHSL or HELGFKVVL.
- the subject expresses an MHC encoded by an HLA-B*40:02 allele and the cancer-specific CD8+ T cell epitope is KEFAFLEHSL or HELGFKVVL. In some embodiments, the subject expresses an MHC encoded by an HLA-B*44:02 allele and the cancerspecific CD8+ T cell epitope is KEFAFLEHSL or HELGFKVVL.
- the subject expresses an MHC encoded by an HLA-A*03:01 allele and the cancer-specific CD8+ T cell epitope is SLYQTIRLK, KTPLHTLLK, RLHSFTLRQK or RVFTSSLKTK.
- the subject expresses an MHC encoded by an HLA-B*07:02 allele and the cancer-specific CD8+ T cell epitope is RPASPRPAP.
- the subject expresses an MHC encoded by an HLA-C*03:04 allele and the cancer-specific CD8+ T cell epitope is IATKIALQM.
- the subject expresses an MHC encoded by an HLA-A*03:01 allele and the cancer-specific CD8+ T cell epitope is LKPDHIQR, RVSLPKLGYK, SLFGARPGR, KSYSKVLVR, MTYKIHFKK, or KTEVHGRLK.
- the subject expresses an MHC encoded by an HLA-A*31 :01 allele and the cancer-specific CD8+ T cell epitope is SLFGARPGR.
- the subject expresses an MHC encoded by an HLA-B*07:02 allele and the cancer-specific CD8+ T cell epitope is SPSSASLAL, RPASPRPAP, NLRPPTQEL, VPASPALSR, SPSARPPSL, SPTLNVSAL, or KPRPDVTNEL.
- the subject expresses an MHC encoded by an HLA-C*07:02 allele and the cancer-specific CD8+ T cell epitope is LRPPTQEL.
- the subject expresses an MHC encoded by an HLA-C*07:02 allele and the cancer-specific CD8+ T cell epitope is KPRPDVTNEL or NLRPPTQEL.
- the subject expresses an MHC encoded by an HLA-C*03:03 allele and the cancer-specific CD8+ T cell epitope is NLRPPTQEL.
- the subject expresses an MHC encoded by an HLA-B*15:01 allele and the cancer-specific CD8+ T cell epitope is GQHLHLETF.
- the subject expresses an MHC encoded by an HLA-C*03:04 allele and the cancer-specific CD8+ T cell epitope is IATKIALQM.
- the subject expresses an MHC encoded by an HLA-C*07:02 allele and the cancer-specific CD8+ T cell epitope is LRPPTQEL.
- the subject expresses an MHC encoded by an HLA-A*03:01 allele and the cancer-specific CD8+ T cell epitope is LKPDHIQR, RVSLPKLGYK, SLFGARPGR, KTEVHGRLK, RLHSFTLRQK, RVFTSSLKTK, RVLAKGLAK, KTPLHTLLK, KSYSKVLVR, MTYKIHFKK, or SLYQTIRLK.
- the subject expresses an MHC encoded by an HLA-B*07:02 allele and the cancer-specific CD8+ T cell epitope is SPSSASLAL, KPRPDVTNEL, NLRPPTQEL, RPASPRPAP, GPRPSPTRSV, SPRSPSPSL, VPQEAVRAPL, VPASPALSR, SPSARPPSL, SPTLNVSAL, or SPSSASLTL.
- the subject expresses an MHC encoded by an HLA-B*08:01 allele and the cancer-specific CD8+ T cell epitope is LNKVKTSL or NLKTHLRL.
- the subject expresses an MHC encoded by an HLA-C*07:01 allele and the cancer-specific CD8+ T cell epitope is FRGVFVHRY.
- the subject expresses an MHC encoded by an HLA-B*35:01 allele and the cancer-specific CD8+ T cell epitope is TSGPVTEKY.
- the subject expresses an MHC encoded by an HLA-A*02:05 allele and the cancer-specific CD8+ T cell epitope is VVAAHLAGA.
- the cancer can be a cancer selected from selected from a colorectal cancer, prostate cancer, esophageal cancer, liver cancer, renal cancer, lung cancer, bladder cancer, breast cancer, pancreatic cancer, brain cancer, hepatocellular cancer, lymphoma, leukaemia, gastric cancer, cervical cancer, ovarian cancer, thyroid cancer, melanoma, carcinoma, head and neck cancer, skin cancer, nasopharyngeal cancer, Epstein Barr driven cancers, Human Papilloma virus driven cancers and soft tissue sarcoma.
- the polynucleotide can be a vector.
- the present disclosure provides a composition comprising a recombinant polypeptide or a polynucleotide encoding the recombinant polypeptide, wherein the recombinant polypeptide comprises a cancer-specific CD8+ T cell epitope which can include e.g.
- GVYDGREHTV KLVELEHTL, LKPDHIQR, RVSLPKLGYK, SLFGARPGR, KTEVHGRLK, SLFGARPGR, SPSSASLAL, RPASPRPAP, NLRPPTQEL, KPRPDVTNEL, KEFAFLEHSL, HELGFKVVL, LRPPTQEL, IATKIALQM, SLYQTIRLK, KTPLHTLLK, RLHSFTLRQK, RVFTSSLKTK, RVLAKGLAK, GPRPSPTRSV, GQHLHLETF, SPRSPSPSL, VPQEAVRAPL, SPSSASLTL, LNKVKTSL, NLKTHLRL, FRGVFVHRY, TSGPVTEKY, KSYSKVLVR, MTYKIHFKK, VPASPALSR, SPSARPPSL, SPTLNVSAL, and/ or VVAAHLAGA or any combination thereof.
- the present disclosure provides a composition comprising a recombinant polypeptide or a polynucleotide encoding the recombinant polypeptide, wherein the recombinant polypeptide or the recombinant polypeptide encoded by the polynucleotide comprises a cancerspecific CD8+ T cell epitope which can include GVYDGREHTV, KLVELEHTL, LKPDHIQR, RVSLPKLGYK, SLFGARPGR, KTEVHGRLK, SLFGARPGR, SPSSASLAL, RPASPRPAP, NLRPPTQEL, KPRPDVTNEL, KEFAFLEHSL, HELGFKVVL, and/ or LRPPTQEL, or any combination thereof.
- a cancerspecific CD8+ T cell epitope which can include GVYDGREHTV, KLVELEHTL, LKPDHIQR, RVSLPKLGYK, SLFGARPGR, KTEVHGRLK, SLFGARPGR
- the composition comprises the recombinant polypeptide or the recombinant polypeptide encoded by the polynucleotide comprises a single cancer-specific CD8+ T cell epitope which can include e g., GVYDGREHTV, KLVELEHTL, SPSSASLAL, KPRPDVTNEL, KEFAFLEHSL and/or HELGFKVVL, or any combination thereof.
- a single cancer-specific CD8+ T cell epitope which can include e g., GVYDGREHTV, KLVELEHTL, SPSSASLAL, KPRPDVTNEL, KEFAFLEHSL and/or HELGFKVVL, or any combination thereof.
- the composition comprises the recombinant polypeptide or the recombinant polypeptide encoded by the polynucleotide comprises a single cancer-specific CD8+ T cell epitope which can include e g., LKPDHIQR, SLFGARPGR, KTEVHGRLK, NLRPPTQEL, RVSLPKLGYK, and/or LRPPTQEL, or any combination thereof.
- the composition comprises the recombinant polypeptide or the recombinant polypeptide encoded by the polynucleotide comprises a single cancer-specific CD8+ T cell epitope which can include e g., RPASPRPAP, IATKIALQM, SLYQTIRLK, KTPLHTLLK, RLHSFTLRQK, and/or RVFTSSLKTK, or any combination thereof.
- the recombinant polypeptide or the recombinant polypeptide encoded by the polynucleotide comprises a single cancer-specific CD8+ T cell epitope which can include e g. IATKIALQM, SLYQTIRLK, KTPLHTLLK, RLHSFTLRQK, RVFTSSLKTK, RVLAKGLAK, GPRPSPTRSV, GQHLHLETF, SPRSPSPSL, VPQEAVRAPL, SPSSASLTL, LNKVKTSL, NLKTHLRL, FRGVFVHRY, TSGPVTEKY, and/ or VVAAHLAGA or any combination thereof.
- a single cancer-specific CD8+ T cell epitope which can include e g. IATKIALQM, SLYQTIRLK, KTPLHTLLK, RLHSFTLRQK, RVFTSSLKTK, RVLAKGLAK, GPRPSPTRSV, GQHLHLETF, SPRSPSPSL, VP
- the present disclosure provides a composition comprising a vector encoding a recombinant polypeptide or a polynucleotide encoding the recombinant polypeptide, wherein the recombinant polypeptide comprises c a cancer-specific CD8+ T cell epitope which can include e g.
- GVYDGREHTV KLVELEHTL, LKPDHIQR, RVSLPKLGYK, SLFGARPGR, KTEVHGRLK, SLFGARPGR, SPSSASLAL, RPASPRPAP, NLRPPTQEL, KPRPDVTNEL, KEFAFLEHSL, HELGFKVVL, LRPPTQEL, IATKIALQM, SLYQTIRLK, KTPLHTLLK, RLHSFTLRQK, RVFTSSLKTK, RVLAKGLAK, GPRPSPTRSV, GQHLHLETF, SPRSPSPSL, VPQEAVRAPL, SPSSASLTL, LNKVKTSL, NLKTHLRL, FRGVFVHRY, TSGPVTEKY, KSYSKVLVR, MTYKIHFKK, VPASPALSR, SPSARPPSL, SPTLNVSAL, and/ or VVAAHLAGA or any combination thereof.
- the vector encodes a single cancer-specific CD8+ T cell epitope which can include e.g. GVYDGREHTV, KLVELEHTL, LKPDHIQR, RVSLPKLGYK, SLFGARPGR, KTEVHGRLK, SLFGARPGR, SPSSASLAL, RPASPRPAP, NLRPPTQEL, KPRPDVTNEL, KEFAFLEHSL, HELGFKVVL, and/ or LRPPTQEL, or any combination thereof.
- GVYDGREHTV e.g. GVYDGREHTV, KLVELEHTL, LKPDHIQR, RVSLPKLGYK, SLFGARPGR, KTEVHGRLK, SLFGARPGR, SPSSASLAL, RPASPRPAP, NLRPPTQEL, KPRPDVTNEL, KEFAFLEHSL, HELGFKVVL, and/ or LRPPTQEL, or any combination thereof.
- the vector encodes a single cancer-specific CD8+ T cell epitope which can include e.g., GVYDGREHTV, KLVELEHTL, SPSSASLAL, KPRPDVTNEL, KEFAFLEHSL and/or HELGFKVVL, or any combination thereof.
- a single cancer-specific CD8+ T cell epitope which can include e.g., GVYDGREHTV, KLVELEHTL, SPSSASLAL, KPRPDVTNEL, KEFAFLEHSL and/or HELGFKVVL, or any combination thereof.
- the vector encodes a single cancer-specific CD8+ T cell epitope which can include e.g., LKPDHIQR, SLFGARPGR, KTEVHGRLK, NLRPPTQEL, RVSLPKLGYK, and/or LRPPTQEL, or any combination thereof.
- the vector encodes a single cancer-specific CD8+ T cell epitope which can include e.g., RPASPRPAP, IATKIALQM, SLYQTIRLK, KTPLHTLLK, RLHSFTLRQK, and/or RVFTSSLKTK or any combination thereof.
- a single cancer-specific CD8+ T cell epitope which can include e.g., RPASPRPAP, IATKIALQM, SLYQTIRLK, KTPLHTLLK, RLHSFTLRQK, and/or RVFTSSLKTK or any combination thereof.
- the vector encodes a single cancer-specific CD8+ T cell epitope which can include e.g., IATKIALQM, SLYQTIRLK, KTPLHTLLK, RLHSFTLRQK, RVFTSSLKTK, RVLAKGLAK, GPRPSPTRSV, GQHLHLETF, SPRSPSPSL, VPQEAVRAPL, SPSSASLTL, LNKVKTSL, NLKTHLRL, FRGVFVHRY, TSGPVTEKY, and/ or VVAAHLAGA or any combination thereof.
- a single cancer-specific CD8+ T cell epitope which can include e.g., IATKIALQM, SLYQTIRLK, KTPLHTLLK, RLHSFTLRQK, RVFTSSLKTK, RVLAKGLAK, GPRPSPTRSV, GQHLHLETF, SPRSPSPSL, VPQEAVRAPL, SPSSASLTL, LNKVKTSL, NLKTHLRL, F
- the cancer-specific CD8+ T cell epitope can be an esophageal cancer-specific CD8+ T cell epitope.
- the vector can be a vector selected from a plasmid, a cosmid, a bacterial vector, a viral vector, an artificial chromosome, a liposome, a lipid nanoparticle, or an exosome.
- the viral vector can be a viral vector, e.g., an adenovirus vector, e.g., an Ad5 vector, e.g., a replication deficient Adhu5 vector.
- the vector is an adenoviral-associated (AAV) vector.
- AAV adenoviral-associated vector.
- the recombinant polypeptide is from 8 to 100 amino acids in length. In some embodiments, the recombinant polypeptide can be from 8 to 100 amino acids in length, e.g., 8 to 12 amino acids in length, e.g., 9 to 10 amino acids in length, e.g., 9 amino acids in length or 10 amino acids in length.
- the cancer-specific CD8+ T cell epitope can bind to a MHC class I molecule, e.g., a with a binding affinity of 500 nM or less.
- the cancer-specific CD8+ T cell epitope can bind to a MHC class I molecule, e.g., a with a predicted binding rank score of 2% or less.
- the recombinant polypeptide can comprise a single cancer-specific CD8+ T cell epitope.
- the vector can encode a single cancer-specific CD8+ T cell epitope.
- the recombinant polypeptide can comprise at least two different cancer-specific CD8+ T cell epitopes.
- the recombinant polypeptide can comprise at least two different recombinant polypeptides.
- each polypeptide can comprise a cancer-specific CD8+ T cell epitope.
- composition can further comprise an adjuvant.
- the method can further comprise administering a second therapeutic agent, e.g., an immune checkpoint inhibitor.
- a second therapeutic agent e.g., an immune checkpoint inhibitor.
- the polynucleotide encoding the recombinant polypeptide can be DNA.
- the polynucleotide encoding the recombinant polypeptide can be RNA, e.g., mRNA. In some embodiments, the polynucleotide encoding the recombinant polypeptide is from 18 to 45 nucleotides in length.
- the composition can be for use in treating a cancer, e.g., a cancer selected from a colorectal cancer, prostate cancer, esophageal cancer, liver cancer, renal cancer, lung cancer, bladder cancer, breast cancer, pancreatic cancer, brain cancer, hepatocellular cancer, lymphoma, leukaemia, gastric cancer, cervical cancer, ovarian cancer, thyroid cancer, melanoma, carcinoma, head and neck cancer, skin cancer, nasopharyngeal cancer, Epstein Barr driven cancers, Human Papilloma virus driven cancers and soft tissue sarcoma, e.g., an esophageal cancer.
- a cancer selected from a colorectal cancer, prostate cancer, esophageal cancer, liver cancer, renal cancer, lung cancer, bladder cancer, breast cancer, pancreatic cancer, brain cancer, hepatocellular cancer, lymphoma, leukaemia, gastric cancer, cervical cancer, ovarian cancer, thyroid cancer, melanoma, carcinoma
- the composition can be for use in treating a virally driven cancer.
- the virally driven cancer may be a cancer caused by HPV (human papilloma virus), HTLV (human T-lymphotropic virus), or EBV (Epstein Barr virus).
- the composition can induce epitope-specific T cell response and/or an inflating memory CD8+ T cell response when administered to a subject.
- the composition can be capable of inducing production of CD8+ T cells characterized by markers which can include e.g., CX3CR1+, KLRG-1+, CD44+, and/or CD62L-, or any combination thereof
- the composition can be capable of inducing production of CD8+ T cells characterized by markers which can include CX3CR1+, KLRG-1+, CD44+, CD62L-, CD27-(low), and/or CD127-(low), or any combination thereof.
- the composition can be capable of inducing production of CD8+/CX3CR1+/KLRG-1+/CD44+ T cells. In some embodiments, the composition can be capable of inducing production of CD8+/CX3CR1+/KLRG-1+/CD62L- T cells. In some embodiments, the composition can be capable of inducing production of CD8+/CX3CR1+/KLRG-1+/CD44+/CD62L- T cells.
- the composition can be capable of inducing production of CD8+/CX3CR1+/KLRG-1+/CD44+/CD62L-/CD27- /CD127- T cells, CD8+/CX3CRl+/KLRG-l+/CD44+/CD62L-/CD27(low)/CD127- T cells, CD8+/CX3CR1+/KLRG-1+/CD44+/CD62L-/CD27- /CD127(low) T cells, or CD8+/CX3CRl+/KLRG-l+/CD44+/CD62L-/CD27(low) /CD127(low) T cells.
- the composition can be capable of inducing production of CD8+/CX3CR1+/KLRG-1+ T cells are further characterized by the phenotype CCR7-and/or CD45RA+/-.
- the composition can be capable of inducing production of CD8+/CX3CR1+/KLRG-1+ T cells that have sustained expression of Tbx21 and/or E2f2.
- the composition can be capable of inducing production of CD8+/CX3CR1+/KLRG-1+ T cells that have low expression of Eomes.
- the composition can be capable of inducing production of CD8+/CX3CR1+/KLRG-1+ T cells that can form about 0.01 percent to 20 percent of total circulating CD8+ T cells in the subject.
- the composition can be capable of inducing production of CD8+/CX3CR1+/KLRG-1+ T cells that maintain a memory effector phenotype for at least 30 days.
- the composition can be capable of inducing production of CD8+/CX3CR1+/KLRG-1+ T cells that have low expression of PD-1, Tim-3, and/or Lag-3. [79] In some embodiments, the composition can be capable of inducing production of an inflating memory CD8+ T cell response that can be capable of controlling tumor growth in the subject greater than 50 days after the composition is administered.
- the composition can be capable of inducing production of a nucleotide sequence encoding the cancer specific CD8+ T cell epitope that encodes a polypeptide comprising the cancer specific CD8+ T cell epitope, in some cases where the polypeptide comprising the cancer specific CD8+ T cell epitope is not processed by antigen presenting cells of the subject when administered; and in some cases when a pharmaceutical composition comprising a corresponding viral vector comprising a nucleotide sequence encoding the cancer specific CD8+ T cell epitope that encodes a polypeptide comprising the cancer specific CD8+ T cell epitope that is processed by antigen presenting cells of the subject when administered, the inflating memory CD8+ T cell response is not induced in the subject.
- the cancer-specific CD8+ T cell epitope can be a viral antigen, a tumor associated antigen that is overexpressed in a cancer cell, or an antigen that is mutated in a cancer cell.
- the polypeptide comprising the cancer specific CD8+ T cell epitope can be not processed by antigen presenting cells.
- the viral vector can include a CMV promoter and a TATA box.
- the viral vector can lack a sequence encoding the El and E3 proteins.
- the composition can include at least 2, 3, 4, 5, or 6 vectors, wherein each of the at least 2, 3, 4, 5, or 6 vectors is a viral vector, and wherein each of the at least 2, 3, 4, 5, or 6 viral vectors can encode a different single cancer specific CD8+ T cell epitope.
- the composition can include at least 1, 2, 3, 4, 5, or 6 vectors, wherein each of the at least 1, 2, 3, 4, 5, or 6 vectors is a viral vector, and wherein each of the at least 1, 2, 3, 4, 5, or 6 vectors can encode two different single cancer specific CD8+ T cell epitopes.
- the present disclosure provides a pharmaceutical composition which can include the composition described herein, and a pharmaceutically acceptable carrier, diluent, excipient, or adjuvant.
- the present disclosure provides a method of treating or preventing a cancer which can include administering a therapeutically effective amount of the pharmaceutical composition described herein to a subject in need thereof.
- the present disclosure provides a method of inducing an inflating memory CD8+ T cell response which can include administering a therapeutically effective amount of the pharmaceutical composition described herein to a subject in need thereof, wherein the inflating memory CD8+ T cell response can include production of CD8+/CX3CR1+/KLRG- 1+ T cells.
- the vector or composition can be administered intravenously or intramuscularly.
- the composition can be administered as a single dose.
- the composition can be administered as multiple doses, e.g., in two doses.
- the first dose is a prime dose.
- the first dose elicits a measurable immune response in a subject as compared to the immune response in the subject in the absence of administration of the first dose.
- the second dose is a booster dose.
- the second dose elicits a measurable immune response in a subject as compared to the immune response in the subject in the absence of administration of the second dose.
- the second dose is administered 24 weeks after the first dose.
- the second dose elicits an immune response that is at least 2 fold greater than the immune response elicited by the first dose.
- the composition can be administered prophylactically to the subject.
- the composition can be administered in combination with a second therapeutic agent, e.g., selected from an immune checkpoint inhibitor, a chemotherapeutic agent, a small molecule inhibitor, or radiotherapy.
- a second therapeutic agent e.g., selected from an immune checkpoint inhibitor, a chemotherapeutic agent, a small molecule inhibitor, or radiotherapy.
- the immune check point inhibitor can be an inhibitor of an immune checkpoint protein which can include e.g., CTLA-4, PD-1, PD-L1, PD-L2, TIM-3, LAG-3, B7-H3, B7-H4, B7-H6, A2aR, BTLA, GALS and/or IDO, or any combination thereof.
- an immune checkpoint protein which can include e.g., CTLA-4, PD-1, PD-L1, PD-L2, TIM-3, LAG-3, B7-H3, B7-H4, B7-H6, A2aR, BTLA, GALS and/or IDO, or any combination thereof.
- the method of treating or preventing a cancer further comprises administering a chemotherapy course. In some embodiments, the method of treating or preventing a cancer, further comprises administering a first chemotherapy course and a second chemotherapy course. In some embodiments, the booster dose is administered 2 weeks prior to the second chemotherapy course. [103] In some embodiments, the method of treating or preventing a cancer, further comprises a surgery, e.g., surgical resection. In some embodiments, the booster dose is administered 1 week after post-surgical recovery.
- the present disclosure provides a method of producing the composition described herein comprising (i) synthesising a nucleotide sequence encoding the single cancer specific CD8+ T cell epitope, as a sense and antisense primer, (ii) cloning the nucleotide sequence encoding the single cancer specific CD8+ T cell epitope synthesized in (i) into a first plasmid, (iii) cloning a sequence comprising the nucleotide sequence encoding the single cancer specific CD8+ T cell epitope from the first plasmid of (ii) into a second vector comprising adenoviral DNA.
- the present disclosure provides a method of treating or preventing a cancer that can include administering a composition described herein to a subject in need thereof, wherein at least two viral vectors are present in the pharmaceutical composition at an amount that is not therapeutically effective individually, thereby treating the cancer in the subject.
- the viral vector can comprise a sequence with at least 90% sequence identity to SEQ ID NO: 44 and a sequence with at least 90% sequence identity to SEQ ID NO: 45.
- the viral vector can further comprise a sequence with at least 90% sequence identity to SEQ ID NO: 47 and a sequence with at least 90% sequence identity to SEQ ID NO: 48.
- the present disclosure provides a method of treating cancer in a subject in need thereof comprising administering to the subject a composition comprising: (i) a recombinant polypeptide comprising a cancer-specific CD8+ T cell epitope, wherein the recombinant polypeptide binds to a TCR; (ii) a polynucleotide encoding a recombinant polypeptide comprising a cancer-specific CD8+ T cell epitope wherein the recombinant polypeptide encoded by the polynucleotide binds to a TCR; (iii) a cell comprising a recombinant polypeptide or a polynucleotide of (i) or (ii); (iv) a recombinant polypeptide comprising an antigen binding domain wherein the antigen binding domain binds to a cancer-specific CD8+ T cell epitope; (v) a polynucleotide
- the viral vector comprises one or more of a promoter, a translation initiating sequence, a start codon, a T cell epitope codon, a stop codon, and a polyadenylation sequence, wherein (i) the promoter is selected from a CMV promoter, an RSV promoter, and an EF 1 a promoter, optionally wherein the promoter comprises a sequence as set forth in SEQ ID NO: 36; (ii) the translation initiation sequence comprises a sequence as set forth in SEQ ID NO: 37; and (iii) the polyadenylation sequence comprises a sequence as set forth in SEQ ID NO 43. [HO] In some embodiments, the vector or viral vector comprises a deletion or a functional deletion in the El gene at an El gene locus. In some embodiments, the vector or viral vector comprises a transgene insertion at the El gene locus.
- the method comprises administering to the subject (i) a first adenoviral vector comprising a sequence encoding a single cancer-specific CD8+ T cell epitope having the sequence GVYDGREHTV, and (ii) a second adenoviral vector comprising a sequence encoding a single cancer-specific CD8+ T cell epitope having the sequence KLVELEHTL; wherein the subject expresses an MHC encoded by an HLA-A*02:01 allele.
- the method comprises administering to the subject (i) a first adenoviral vector comprising a sequence encoding a single cancer-specific CD8+ T cell epitope having the sequence SPSSASLAL, and (ii) a second adenoviral vector comprising a sequence encoding a single cancer-specific CD8+ T cell epitope having the sequence KPRPDVTNEL; wherein the subject expresses an MHC encoded by an HLA-B*07:02 allele.
- the method comprises administering to the subject (i) a first adenoviral vector comprising a sequence encoding a single cancer-specific CD8+ T cell epitope having the sequence SPSSASLAL, and (ii) a second adenoviral vector comprising a sequence encoding a single cancer-specific CD8+ T cell epitope having the sequence KPRPDVTNEL; wherein the subject expresses an MHC encoded by an HLA-B*35:03 allele.
- the method comprises administering to the subject (i) a first adenoviral vector comprising a sequence encoding a single cancer-specific CD8+ T cell epitope having the sequence KEFAFLEHSL, and (ii) a second adenoviral vector comprising a sequence encoding a single cancer-specific CD8+ T cell epitope having the sequence HELGFKVVL; wherein the subject expresses an MHC encoded by an HLA-B*40:01 allele.
- the method comprises administering to the subject (i) a first adenoviral vector comprising a sequence encoding a single cancer-specific CD8+ T cell epitope having the sequence KEFAFLEHSL, and (ii) a second adenoviral vector comprising a sequence encoding a single cancer-specific CD8+ T cell epitope having the sequence HELGFKVVL; wherein the subject expresses an MHC encoded by an HLA-B*40:02 allele.
- the method comprises administering to the subject (i) a first adenoviral vector comprising a sequence encoding a single cancer-specific CD8+ T cell epitope having the sequence KEFAFLEHSL, and (ii) a second adenoviral vector comprising a sequence encoding a single cancer-specific CD8+ T cell epitope having the sequence HELGFKVVL; wherein the subject expresses an MHC encoded by an HLA-B*44:02 allele.
- the method comprises administering to the subject (i) a first adenoviral vector comprising a sequence encoding a single cancer-specific CD8+ T cell epitope having the sequence KEFAFLEHSL, and (ii) a second adenoviral vector comprising a sequence encoding a single cancer-specific CD8+ T cell epitope having the sequence HELGFKVVL; wherein the subject expresses an MHC encoded by an HLA-B* 18:01 allele.
- the composition comprises (i) a first adenoviral vector com-prising a sequence encoding a single cancer-specific CD8+ T cell epitope having the sequence GVYDGREHTV, and (ii) a second adenoviral vector comprising a sequence encoding a single cancer-specific CD8+ T cell epitope having the sequence KLVELEHTL.
- the composition is for use in treating esophageal cancer in a subject.
- the composition is for use in treating esophageal cancer in a subject, wherein the subject expresses an MHC encoded by an HLA-A*02:01 allele.
- the composition comprises (i) a first adenoviral vector comprising a sequence encoding a single cancer-specific CD8+ T cell epitope having the se-quence SPSSASLAL, and (ii) a second adenoviral vector comprising a sequence encoding a single cancer-specific CD8+ T cell epitope having the sequence KPRPDVTNEL.
- the composition is for use in treating esophageal cancer in a subject.
- the composition is for use in treating esophageal cancer in a subject, wherein the subject expresses an MHC encoded by an HLA-B*07:02 allele.
- the composition is for use in treating esophageal cancer in a subject, wherein the subject expresses an MHC encoded by an HLA-B*35:03 allele.
- the composition comprises (i) a first adenoviral vector comprising a sequence encoding a single cancer-specific CD8+ T cell epitope having the se-quence KEFAFLEHSL, and (ii) a second adenoviral vector comprising a sequence encoding a single cancer-specific CD8+ T cell epitope having the sequence HELGFKVVL.
- the composition is for use in treating esophageal cancer in a subject.
- the composition is for use in treating esophageal cancer in a subject, wherein the subject expresses an MHC encoded by an HLA-B*40:01 allele.
- the composition is for use in treating esophageal cancer in a subject, wherein the subject expresses an MHC encoded by an HLA-B*40:02 allele.
- the composition is for use in treating esophageal cancer in a subject, wherein the subject expresses an MHC encoded by an HLA-B*44:02 allele.
- the composition is for use in treating esophageal cancer in a subject, wherein the subject expresses an MHC encoded by an HLA-B* 18:01 allele.
- the first adenoviral vector is and Ad5 adenoviral vector and/or the second adenoviral vector is and Ad5 adenoviral vector.
- the first adenoviral vector comprises a deletion or a functional deletion in the El gene at an El gene locus and/or the second adenoviral vector comprises a deletion or a functional deletion in the El gene at an El gene locus.
- FIG. 1 shows a schematic diagram of the proposed clinical trial protocol.
- FIG. 2 shows a schematic diagram of a proposed clinical trial study design.
- FIG. 3 shows events at timepoints of a proposed clinical trial design.
- TAAs tumor associated antigens
- the present disclosure provides recombinant polypeptides comprising at least one T cell epitope, e.g., a CD8+ T cell epitope, e.g., a cancer-specific CD8+ T cell epitope, polynucleotides encoding the T cell epitopes, e.g., a CD8+ T cell epitopes, vectors, cells, compositions, pharmaceutical compositions, formulation, and methods of using such.
- T cell epitope e.g., a CD8+ T cell epitope, e.g., a cancer-specific CD8+ T cell epitope
- polynucleotides encoding the T cell epitopes e.g., a CD8+ T cell epitopes
- vectors cells, compositions, pharmaceutical compositions, formulation, and methods of using such.
- references to “some embodiments”, “an embodiment”, “one embodiment”, or “other embodiments” means that a particular feature or characteristic described in connection with the embodiments is included in at least one or more embodiments, but not necessarily all embodiments, of the present disclosure.
- the term “about” or “approximately” as disclosed herein refers to in relation to a numerical value means a range of values that fall within 15% greater than or 15% less than the value.
- Ranges throughout this disclosure, various aspects of the present disclosure can be presented in a range format. It should be understood that the description in range format is merely for convenience and brevity and should not be construed as an inflexible limitation on the scope of the present disclosure. Accordingly, the description of a range should be considered to have specifically disclosed all the possible subranges as well as individual numerical values within that range. For example, description of a range such as from 1 to 6 should be considered to have specifically disclosed subranges such as from 1 to 3, from 1 to 4, from 1 to 5, from 2 to 4, from 2 to 6, from 3 to 6 etc., as well as individual numbers within that range, for example, 1, 2, 2.7, 3, 4, 5, 5.3, and 6.
- a range such as 95-99% identity includes something with 95%, 96%, 97%, 98% or 99% identity, and includes subranges such as 96-99%, 96-98%, 96-97%, 97-99%, 97-98% and 98-99% identity. This applies regardless of the breadth of the range.
- determining As used herein, the terms “determining,” “measuring,” “evaluating,” “assessing,” “assaying,” and “analyzing” are often used interchangeably herein to refer to forms of measurement.
- the terms include determining if an element is present or not (for example, detection). These terms can include quantitative, qualitative or quantitative and qualitative determinations. Assessing can be relative or absolute. “Detecting the presence of can include determining the amount of something present in addition to determining whether it is present or absent depending on the context.
- cancer refers to diseases with abnormal cell growth, as used herein the term refers to both a primary tumor and metastasis of the primary tumor. Cancer cells can spread locally or through the bloodstream and lymphatic system to other parts of the body.
- cancers include but are not limited to colorectal cancer, prostate cancer, esophageal cancer, liver cancer, renal cancer, lung cancer, breast cancer, breast cancer, pancreatic cancer, brain cancer, hepatocellular cancer, lymphoma, leukemia, gastric cancer, cervical cancer, ovarian cancer, thyroid cancer, melanoma, carcinoma, head and neck cancer, skin cancer, nasopharyngeal cancer, Epstein Barr driven cancers, Human Papilloma virus driven cancers and soft tissue sarcoma.
- the cancer described herein can be a stage I cancer, a stage II cancer, a stage III cancer, or a stage IV cancer.
- the term “tumor” refers to the physiological condition in mammals characterized by deregulated cell growth.
- the term “individual,” “patient,” or “subject” refers to individuals diagnosed with, suspected of being afflicted with, or at-risk of developing at least one disease for which the described compositions and methods are useful for treating. In certain embodiments, the individual is a human.
- the individual is a mammal.
- the mammal is a non-human primate (e.g., rhesus or other types of macaques), mouse, rat, rabbit, dog, cat, horse, cow, sheep, pig, goat, llama, alpaca, or yak.
- the individual is a human.
- linker refers to a molecule linking two other molecules or moi eties.
- the linker can be an amino acid sequence in the case of a linker joining two fusion proteins.
- the linker can also be a nucleotide sequence in the case of joining two nucleotide sequences together.
- a linker may have various lengths, depending on the application of a linker or the sequences or molecules being linked by a linker.
- treatment or “treating” are used in reference to a pharmaceutical or other intervention regimen used for obtaining beneficial or desired results in the recipient.
- beneficial or desired results include but are not limited to a therapeutic benefit and/or a prophylactic benefit.
- a therapeutic benefit may refer to eradication or amelioration of symptoms or of an underlying disorder being treated.
- a therapeutic benefit can be achieved with the eradication or amelioration of one or more of the physiological symptoms associated with the underlying disorder such that an improvement is observed in the subject, notwithstanding that the subject may still be afflicted with the underlying disorder.
- a prophylactic effect includes delaying, preventing, or eliminating the appearance of a disease or condition, delaying or eliminating the onset of symptoms of a disease or condition, slowing, halting, or reversing the progression of a disease or condition, or any combination thereof.
- a subject at risk of developing a particular disease, or to a subject reporting one or more of the physiological symptoms of a disease may undergo treatment, even though a diagnosis of this disease may not have been made. Skilled artisans will recognize that given a population of potential individuals for treatment not all will respond or respond equally to the treatment. Such individuals are considered treated if administered the compositions including the pharmaceutical compositions described herein.
- the term “effective amount”, “therapeutically effective amount” or “pharmaceutically effective amount” refers to an amount that is sufficient to effect treatment, as defined below, when administered to a subject (e.g., a mammal, such as a human) in need of such treatment.
- the therapeutically or pharmaceutically effective amount will vary depending upon the subject and disease condition being treated, the weight and age of the subject, the severity of the disease condition, the manner of administration and the like, which can readily be determined by one of ordinary skill in the art.
- a “therapeutically effective amount” or a “pharmaceutically effective amount” of AAV2-derived capsid as described herein is an amount sufficient to generate an immune response in a subject (e.g., a human).
- the immune response is sufficient to raise AAV capsid neutralizing antibodies against the relevant capsid(s) in the subject.
- sequence identity refers to the subunit sequence identity between two polymeric molecules, for example, between two polynucleotide or polypeptide sequences.
- An analysis of sequence identity begins by aligning two sequences. Identical sequences (100% sequence identity) have the same nucleotide or amino acid at each position of the alignment.
- Percent sequence identity is determined by comparing the number of positions that are identical to the total number of subunits in the sequence alignment. Percent sequence identity can be determined over a fraction of the sequences or over the whole of the sequences. Percent sequence identity can be determined using a sequence comparison algorithm. Test and reference sequences are input into a computer, subsequence coordinates are designated, if necessary, and sequence algorithm program parameters are designated. The sequence comparison algorithm then aligns the sequences and calculates the percent sequence identity based on the designated program parameters.
- Sequence identity is typically measured using sequence analysis software. Optimal alignment of sequences for comparison can be conducted, e.g., by the local homology algorithm of Smith & Waterman, Adv. Appl. Math. 2:482 (1981), by the homology alignment algorithm of Needleman & Wunsch, J. Mol. Biol. 48:443 (1970), by the search for similarity method of Pearson & Lipman, Proc. Nat’l. Acad. Sci.
- sequence identities are determined by Needleman-Wunsch alignment of two sequences with Gap Costs set to Existence: 11 Extension: 1 where percent identity is calculated by dividing the number of identities by the length of the alignment.
- Conservative substitutions typically include substitutions within the following groups: glycine, alanine; valine, isoleucine, leucine; aspartic acid, glutamic acid, asparagine, glutamine; serine, threonine; lysine, arginine; and phenylalanine, tyrosine.
- the term “antigen presenting cell” or “APC” refers to an immune system cell such as an accessory cell (e.g., a B-cell, a dendritic cell, and the like) that displays a foreign antigen complexed with major histocompatibility complexes (MHC’s) on its surface.
- T cells may recognize these complexes using their T cell receptors (TCRs).
- TCRs T cell receptors
- the term “encoding” refers to the inherent property of specific sequences of nucleotides in a polynucleotide, such as a gene, a cDNA, or an mRNA, to serve as templates for synthesis of other polymers and macromolecules in biological processes having either a defined sequence of nucleotides (e.g., rRNA, tRNA, and mRNA) or a defined sequence of amino acids and the biological properties resulting therefrom.
- a gene, cDNA, or RNA encodes a protein if transcription and translation of mRNA corresponding to that gene produces the protein in a cell or other biological system.
- Both the coding strand the nucleotide sequence of which is identical to the mRNA sequence and is usually provided in sequence listings, and the non-coding strand, used as the template for transcription of a gene or cDNA, can be referred to as encoding the protein or other product of that gene or cDNA.
- nucleotide sequence encoding an amino acid sequence includes all nucleotide sequences that are degenerate versions of each other and that encode the same amino acid sequence.
- the phrase nucleotide sequence that encodes a protein or an RNA may also include introns to the extent that the nucleotide sequence encoding the protein may in some version contain one or more introns.
- T cell and its grammatical equivalents as used herein can refer to a T cell from any origin.
- a T cell can be a primary T cell, e.g., an autologous T cell, an allogenic T cell, a cell line, etc.
- the T cell can also be human or non-human in origin.
- CD8 refers to the Cluster of Differentiation 8 protein, a transmembrane glycoprotein that serves as a co-receptor for the T-cell receptor (TCR).
- effector T cell includes T helper (e.g., CD4+) cells and cytotoxic (e.g., CD8+) T cells.
- T helper e.g., CD4+
- cytotoxic e.g., CD8+
- CD4+ effector T cells contribute to the development of several immunologic processes, including maturation of B cells into plasma cells and memory B cells, and activation of cytotoxic T cells and macrophages.
- CD8+ effector T cells destroy virus- infected cells and tumor cells.
- nucleic acid or “polynucleotide” refers to deoxyribonucleic acids (DNA) or ribonucleic acids (RNA) and polymers thereof in either single- or doublestranded form. Unless specifically limited, the term encompasses nucleic acids containing known analogues of natural nucleotides that have similar binding properties as the reference nucleic acid and are metabolized in a manner similar to naturally occurring nucleotides. Unless otherwise indicated, a particular nucleic acid sequence also implicitly encompasses conservatively modified variants thereof (e.g., degenerate codon substitutions), alleles, orthologs, SNPs, and complementary sequences as well as the sequence explicitly indicated.
- DNA deoxyribonucleic acids
- RNA ribonucleic acids
- degenerate codon substitutions may be achieved by generating sequences in which the third position of one or more selected (or all) codons is substituted with mixed-base and/or deoxyinosine residues (Batzer et al., Nucleic Acid Res. 19:5081 (1991); Ohtsuka et al., J. Biol. Chem. 260:2605-2608 (1985); and Rossolini et al., Mol. Cell. Probes 8:91-98 (1994)).
- peptide As used herein, the terms “peptide,” “polypeptide,” and “protein” are used interchangeably, and refer to a compound comprised of amino acid residues covalently linked by peptide bonds.
- a protein or peptide must contain at least two amino acids, and no limitation is placed on the maximum number of amino acids that can comprise a protein’s or peptide’s sequence.
- Polypeptides include any peptide or protein comprising two or more amino acids joined to each other by peptide bonds.
- the term refers to both short chains, which also commonly are referred to in the art as peptides, oligopeptides and oligomers, for example, and to longer chains, which generally are referred to in the art as proteins, of which there are many types.
- Polypeptides include, for example, biologically active fragments, substantially homologous polypeptides, oligopeptides, homodimers, heterodimers, variants of polypeptides, modified polypeptides, derivatives, analogs, fusion proteins, among others.
- a polypeptide includes a natural peptide, a recombinant peptide, or a combination thereof.
- promoter refers to a DNA sequence recognized by the transcription machinery of the cell, or introduced synthetic machinery, required to initiate the specific transcription of a polynucleotide sequence.
- promoter/regulatory sequence refers to a nucleic acid sequence which is required for expression of a gene product operably linked to the promoter/regulatory sequence. In some instances, this sequence may be the core promoter sequence and in other instances, this sequence may also include an enhancer sequence and other regulatory elements which are required for expression of the gene product.
- the promoter/regulatory sequence may, for example, be one which expresses the gene product in a tissue specific manner.
- vector refers to a nucleic acid sequence capable of transporting into a cell another nucleic acid to which the vector sequence has been linked.
- vectors are known in the art including, but not limited to, linear polynucleotides, polynucleotides associated with ionic or amphiphilic compounds, plasmids, and viruses.
- viral vectors include, but are not limited to, adenoviral vectors, adeno-associated virus vectors (AAVs), retroviral vectors, lentiviral vectors, and the like.
- a vector of the present disclosure can be adenoviral and comprises the nucleotide sequence encoding a single cancer specific CD8+ T cell epitope containing a gene construct in a form suitable for expression by a cell (e.g., linked to a transcriptional control element).
- epitope refers to a part of an antigen that is recognized by the immune system which may be a short protein sequence.
- a “cancer specific CD8+ T cell epitope” refers to an epitope that may be presented by an antigen presenting cell bound to an MHC molecule which are then recognized by the T-cell receptor (TCR).
- CD8+ T cells express the CD8 coreceptor, which binds to MHC I, and recognize peptides presented by MHC I molecules.
- HLA binding affinity or “MHC binding affinity” means affinity of binding between a specific antigen and a specific MHC allele.
- HLAbinding rank score or “MHC binding rank score” means the predicted rank score.
- the predicted rank score is a percentage rank position of a query sequence (antigen) in relation to a distribution of prediction scores for the MHC in question, estimated from a set of random natural peptides. A rank score below the value of 2% indicates binding between a specific antigen and a specific MHC allele.
- recombinant polypeptides or polynucleotides encoding the recombinant polypeptide
- a T cell epitope that is capable of binding to one or more MHC molecules, presented by the one or more MHC molecules, being immunogenic and/or capable of activating T cells to become cytotoxic and compositions thereof.
- an epitope described herein may bind to a MHC (e.g., a MHC class I) molecule with a rank score (e.g., a binding rank score) of at least about 0.5%, at least about 1%, at least about 1.5%, at least about 2%, at least about 2.5%, at least about 3%, at least about 3.5%, at least about 4%, at least about 5%, or greater than about 5%.
- a MHC e.g., a MHC class I
- a rank score e.g., a binding rank score
- an epitope described herein may bind to a MHC (e.g., a MHC class I) molecule with a rank score (e.g., a binding rank score) of at most about 5%, at most about 4%, at most about 3.5%, at most about 3%, at most about 2.5%, at most about 2%, at most about 1.5%, at most about 1%, at most about 0.5%, or less than about 0.5%.
- MHC e.g., a MHC class I
- a rank score e.g., a binding rank score
- the present disclosure provides a recombinant polypeptide comprising a single epitope, e.g., a single T cell epitope, e.g., a single cancer-specific CD8+ and/or a CD4+ epitope, e.g., a single cancer-specific CD8+ epitope.
- a single epitope e.g., a single T cell epitope, e.g., a single cancer-specific CD8+ and/or a CD4+ epitope, e.g., the single cancer-specific CD8+ epitope is an immunogenic epitope, e.g., it elicits an immune response.
- the single epitope e.g., the single T cell epitope, e.g., the single cancer-specific CD8+ and/or a CD4+ epitope, e.g., the single cancer-specific CD8+ epitope binds to a major histocompatibility complex (MHC complex), e.g., an MHC associated with a cell, e.g., a cancer cell.
- MHC complex major histocompatibility complex
- the single epitope e.g., the single T cell epitope, e.g., the single cancer-specific CD8+ and/or a CD4+ epitope, e.g., the single cancer-specific CD8+ epitope is capable of binding and presenting on an MHC molecule, an MHC molecule associated with a cell, e.g., a cancer cell.
- MHC molecules are highly polymorphic proteins that regulate T cell responses (Schwartz, B. D., The human major histocompatibility complex HLA in basic & clinical immunology Stites et al, eds., Lange Medical Publication: Los Altos, pp. 52-64, 4th ed.).
- the MHC system is responsible for presenting epitopes to responding T cells.
- the species-specific MHC homologues that display cytotoxic T-cell lymphocyte (CD8+) epitopes or helper T-cell lymphocyte (CD4+) epitopes in humans are termed human leukocyte antigen (“HLA”).
- HLA class I and class II molecules can be divided into several families or “supertypes” based upon their ability to bind similar repertoires of peptides.
- HLA class I HLA-A, -B, and -C
- HLA class II HLA-DP, -DQ, and -DR
- CD4+ T cell which may then initiate an immune response towards the presenting cell.
- the tumor-specific peptide In order to trigger an immune response, the tumor-specific peptide must be bound to an MHC molecule. This binding is dependent on the allele of the MHC molecule and specific polymorphisms of the amino acid sequence of the epitope.
- the recombinant polypeptide can comprise a cancer-specific CD8+ T cell epitope that can bind to a MHC class I molecule. In some cases, the recombinant polypeptide can comprise a cancer-specific CD4+ T cell epitope that can bind to a MHC class II molecule.
- the epitope e.g., the single T cell epitope, e.g., the single cancerspecific CD8+ epitope binds to an MHC encoded by an HLA, e.g., an HLA-A allele, e.g., an HLA-B allele, e.g., an HLA-C allele.
- the HLA-A allele is an HLA-A* 11 allele (e.g., an HLA-A* 11 :01 allele), an HLA-A*02 allele (e.g., an HLA-A*02:01 allele, e.g., an HLA-A*02:05 allele), an HLA-A*03 allele (e.g., an HLA-A*03:01 allele,), or an HLA-A*31 allele (e.g., an HLA-A*31 :01 allele).
- HLA-A* 11 allele e.g., an HLA-A* 11 :01 allele
- an HLA-A*02 allele e.g., an HLA-A*02:01 allele, e.g., an HLA-A*02:05 allele
- an HLA-A*03 allele e.g., an HLA-A*03:01 allele
- HLA-A*31 allele e.g
- the HLA-B allele is an HLA-B*07 allele (e.g., an HLA-B*07:02 allele), an HLA-B*08 allele (e.g., an HLA-B*08:01 allele), an HLA-B*15 allele (e.g., an HLA-B*15:01 allele), an HLA-B*18 allele (e.g., an HLA-B*18:01 allele), an HLA-B*35 allele (e.g., an HLA-B*35:01 allele, an HLA-B*35:03 allele), an HLA- B*40 allele (e.g., an HLA-B*40:01 allele, e.g., an HLA-B*40:02 allele), or an HLA-B*44 allele (e.g., an HLA-B*44:01 allele, e.g., an HLA-B*44:02 allele).
- the HLA-C allele is an HLA-C*03 allele, (e.g. an HLA-C*03:04 allele), or an HLA-C*07 allele, (e.g., an HLA-C*07:01 allele, e.g., an HLA-C*07:02 allele).
- the single T cell epitope e.g., the single cancer-specific CD8+ and/or CD4+ epitope, e.g., the single cancerspecific CD8+ epitope can bind to multiple MHCs encoded by different HLAs, e.g., a single T cell epitope.
- a single T cell epitope e.g., a single cancer-specific CD8+ epitope disclosed herein can bind to an MHC encoded by an HLA selected from HLA-B*40:01, HLA-B*44:01, HLA-B*44:02, or HLA-B*18:01.
- the epitope e.g., a single T cell epitope, e.g., a single cancer-specific CD8+ epitope disclosed herein binds to an MHC encoded by an HLAalleles it is predicted to bind to.
- Predicted binding affinities and ranks for MHC molecules can help prioritize peptides for experimental testing.
- Multiple methods are known in the art to predict the binding of peptides to MHC class I and MHC class II complexes and can include, but are not limited to, NetMHC, NetMHCpan, NetMHCllpan, stabilized matrix method (SMM), and/or average relative binding matrix (ARB).
- the predicted binding rank score can be between 4% and less than 0.1% including 0%, between 3.5% and 02%, between 3% and 0.5%, between 2.5% and 1%, between 2.25% and 1.5%, between 2% and 1%, between 2% and 0.5%, between 0.5% and 0.4%, between 0.4% and 0.3%, between 0.3% and 0.2%, between 0.2% and 0.1%, or less than 0.1% including 0%.
- the binding affinity can be about 500 nM or less than 500 nM.
- the binding affinity can be about between 500 nM and 400 nM, about between 400 nM and 300 nM, about between 300 nM and 200 nM, about between 200 nM and 100 nM, or about less than 100 nM including 0 nM.
- an epitope described herein may bind to a MHC (e.g., a MHC class I) molecule with a binding affinity of at most about 750 nM, at most about 500 nM, at most about 400 nM, at most about 300 nM, at most about 200 nM, at most about 100 nM, at most about 50 nM, or less than about 50 nM.
- MHC e.g., a MHC class I
- binding of the single epitope, e.g., the single T cell epitope, e.g., the single cancer-specific CD8+ and/or CD4+ epitope, e.g., the single cancer-specific CD8+ epitope to the MHC complex initiates a subsequent immune response, e.g., an inflating memory T cell response, e.g., an inflating memory CD8+ and/or CD4+ T cell response, e.g., an inflating memory CD8+ T cell response.
- a subsequent immune response e.g., an inflating memory T cell response, e.g., an inflating memory CD8+ and/or CD4+ T cell response, e.g., an inflating memory CD8+ T cell response.
- the inflating memory T cell response e.g., the inflating memory CD8+ and/or CD4+ T cell response, e.g., the inflating memory CD8+ T cell response targets cancer cells.
- the recombinant polypeptide comprising the single epitope e.g., the single T cell epitope, e.g., the single cancer-specific CD8+ and/or CD4+ epitope, e.g., the single cancer-specific CD8+ epitope binds an HLA type encoding an MHC of a patient’s cancer cells.
- the recombinant polypeptide comprising the single epitope e.g., the single T cell epitope, e.g., the single cancerspecific CD8+ and/or epitope, e.g., the single cancer-specific CD8+ epitope does not bind to an HLA type encoding an MHC of a patient’s non-cancer cells.
- the recombinant polypeptide comprising the single epitope e.g., the single T cell epitope, e.g., the single cancer-specific CD8+ and/or CD4+ epitope, e.g., the single cancer-specific CD8+ epitope does not cause T cell exhaustion while binding to the HLA type encoding the MHC of the patient’s cancer cells.
- the recombinant polypeptide comprises a single epitope, e.g., a single T cell epitope, e.g., the single cancer-specific CD4+ and/or CD8+ epitope, e.g., a single cancer-specific CD8+ epitope comprising an amino acid sequence selected from Table 1.
- the recombinant polypeptide comprises a single epitope, e.g., a single T cell epitope, e.g., the single cancer-specific CD4+ and/or CD8+ epitope, e.g., a single cancer-specific CD8+ epitope comprising an amino acid sequence as set forth in any of the SEQ ID NOs: 1-35.
- the recombinant polypeptide comprises a single epitope, e.g., a single T cell epitope, e.g., the single cancer-specific CD4+ and/or CD8+ epitope, e.g., a single cancerspecific CD8+ epitope comprising an amino acid sequence with 90-99% identity to an amino acid sequence as set forth in any of the SEQ ID NOs: 1-35.
- the recombinant polypeptide comprises a single epitope, e.g., a single T cell epitope, e.g., the single cancer-specific CD4+ and/or CD8+ epitope, e.g., a single cancer-specific CD8+ epitope comprising an amino acid sequence with 1, 2, or at most 3 amino acid mutations compared to an amino acid sequence as set forth in any of the SEQ ID NOs: 1-35.
- the single epitope e.g., the single T cell epitope, e.g., the single cancer-specific CD4+ and/or CD8+ epitope, e.g., the single cancer-specific CD8+ epitope comprises an amino acid sequence as set forth in any of the SEQ ID NOs: 1-13.
- the recombinant polypeptide comprises a single epitope, e.g., a single T cell epitope, e.g., the single cancer-specific CD4+ and/or CD8+ epitope, e.g., a single cancer-specific CD8+ epitope comprising an amino acid sequence with 90-99% identity to an amino acid sequence as set forth in any of the SEQ ID NOs: 1-13.
- the recombinant polypeptide comprises a single epitope, e.g., a single T cell epitope, e.g., the single cancerspecific CD4+ and/or CD8+ epitope, e.g., a single cancer-specific CD8+ epitope comprising an amino acid sequence with 1, 2, or at most 3 amino acid mutations compared to an amino acid sequence as set forth in any of the SEQ ID NOs: 1-13.
- the single epitope e.g., the single T cell epitope, e.g., the single cancer-specific CD4+ and/or CD8+ epitope, e.g., the single cancer-specific CD8+ epitope comprises an amino acid sequence as set forth in any of the SEQ ID NOs: 1-6.
- the recombinant polypeptide comprises a single epitope, e.g., a single T cell epitope, e.g., the single cancer-specific CD4+ and/or CD8+ epitope, e.g., a single cancer-specific CD8+ epitope comprising an amino acid sequence with 90-99% identity to an amino acid sequence as set forth in any of the SEQ ID NOs: 1-6.
- the recombinant polypeptide comprises a single epitope, e.g., a single T cell epitope, e.g., the single cancerspecific CD4+ and/or CD8+ epitope, e.g., a single cancer-specific CD8+ epitope comprising an amino acid sequence with 1, 2, or at most 3 amino acid mutations compared to an amino acid sequence as set forth in any of the SEQ ID NOs: 1-6.
- the single epitope e.g., the single T cell epitope, e.g., the single cancer-specific CD4+ and/or CD8+ epitope, e.g., the single cancer-specific CD8+ epitope comprises an amino acid sequence as set forth in any of the SEQ ID NOs: 7-12.
- the recombinant polypeptide comprises a single epitope, e.g., a single T cell epitope, e.g., the single cancer-specific CD4+ and/or CD8+ epitope, e.g., a single cancer-specific CD8+ epitope comprising an amino acid sequence with 90-99% identity to an amino acid sequence as set forth in any of the SEQ ID NOs: 7-12.
- the recombinant polypeptide comprises a single epitope, e.g., a single T cell epitope, e.g., the single cancerspecific CD4+ and/or CD8+ epitope, e.g., a single cancer-specific CD8+ epitope comprising an amino acid sequence with 1, 2, or at most 3 amino acid mutations compared to an amino acid sequence as set forth in any of the SEQ ID NOs: 7-12.
- the single epitope e.g., the single T cell epitope, e.g., the single cancer-specific CD8+ epitope comprises an amino acid sequence as set forth in any of the SEQ ID NOs: 13-18.
- the recombinant polypeptide comprises a single epitope, e.g., a single T cell epitope, e.g., a single cancer-specific CD8+ epitope comprising an amino acid sequence with 90-99% identity to an amino acid sequence as set forth in any of the SEQ ID NOs: 13-18.
- the recombinant polypeptide comprises a single epitope, e.g., a single T cell epitope, e.g., a single cancer-specific CD8+ epitope comprising an amino acid sequence with 1, 2, or at most 3 amino acid mutations compared to an amino acid sequence as set forth in any of the SEQ ID NOs: 13-18.
- the single epitope e.g., the single T cell epitope, e.g., the single cancer-specific CD8+ epitope comprises an amino acid sequence selected from any of the SEQ ID NOs: 19-35, an amino acid sequence with 90-99% identity to an amino acid sequence as set forth in any of the SEQ ID NOs: 19-35, or an amino acid sequence with 1, 2, or at most 3 amino acid mutations compared to an amino acid sequence as set forth in any of the SEQ ID NOs: 19-35.
- the single epitope e.g., the single T cell epitope, e.g., the single cancer-specific CD4+ and/or CD8+ epitope, e.g., the single cancer-specific CD8+ epitope comprises an amino acid sequence as set forth in any of the SEQ ID NOs: 1-35.
- the single epitope e.g., the single T cell epitope, e.g., the single cancer-specific CD4+ and/or CD8+ epitope, e.g., the single cancer-specific CD8+ epitope comprises an amino acid sequence with 90-99% identity to an amino acid sequence as set forth in any of the SEQ ID NOs: 1-35.
- the single epitope e.g., the single T cell epitope, e.g., the single cancer-specific CD4+ and/or CD8+ epitope, e.g., the single cancer-specific CD8+ epitope comprises an amino acid sequence 1, 2, or at most 3 amino acid mutations compared to an amino acid sequence as set forth in any of the SEQ ID NOs: 1-35.
- the single cancer-specific T cell epitope may comprise an amino acid sequence having at least about 90%, at least about 91%, at least about 92%, at least about 93%, at least about 94%, at least about 95%, at least about 96%, at least about 97%, at least about 98%, at least about 98.5%, at least about 99%, at least about 99.5%, at least about 99.9%, or greater than about 99.9% sequence identity to an amino acid sequence as set forth in any one of SEQ ID NOs: 1-35.
- the single cancer-specific T cell epitope may comprise an amino acid sequence having at most about 99.9%, at most about 99.5%, at most about 99%, at most about 98.5%, at most about 98%, at most about 97%, at most about 96%, at most about 95%, at most about 94%, at most about 93%, at most about 92%, at most about 91%, at most about 90%, or less than about 90% sequence identity to an amino acid sequence as set forth in any one of SEQ ID NOs: 1-35.
- the single cancer-specific T cell epitope may comprise an amino acid sequence having from about 90% to about 99.9%.
- the single cancer-specific T cell epitope (e.g., the single cancer specific CD8+ T cell epitope) may comprise an amino acid sequence having from about 90% to about 91%, about 90% to about 92%, about 90% to about 93%, about 90% to about 94%, about 90% to about 95%, about 90% to about 96%, about 90% to about 97%, about 90% to about 98%, about 90% to about 99%, about 90% to about 99.5%, about 90% to about 99.9%, about 91% to about 92%, about 91% to about 93%, about 91% to about 94%, about 91% to about 95%, about 91% to about 96%, about 91% to about 97%, about 91% to about 98%, about 91% to about 99%, about 91% to about 99.5%, about 91% to about 99.9%.
- the single epitope e.g., the single T cell epitope, e.g., the single cancer-specific CD4+ and/or CD8+ epitope, e.g., the single cancer-specific CD8+ epitope comprises an amino acid sequence as set forth in any of the SEQ ID NOs: 1-13.
- the single epitope e.g., the single T cell epitope, e.g., the single cancer-specific CD4+ and/or CD8+ epitope, e.g., the single cancer-specific CD8+ epitope comprises an amino acid sequence with 90-99% identity to an amino acid sequence as set forth in any of the SEQ ID NOs: 1-13.
- the single epitope e.g., the single T cell epitope, e.g., the single cancer-specific CD4+ and/or CD8+ epitope, e.g., the single cancer-specific CD8+ epitope comprises an amino acid sequence 1, 2, or at most 3 amino acid mutations compared to an amino acid sequence as set forth in any of the SEQ ID NOs: 1-13.
- the single epitope e.g., the single T cell epitope, e.g., the single cancer-specific CD4+ and/or CD8+ epitope, e.g., the single cancer-specific CD8+ epitope comprises an amino acid sequence as set forth in any of the SEQ ID NOs: 1-6.
- the single epitope e.g., the single T cell epitope, e.g., the single cancer-specific CD4+ and/or CD8+ epitope, e.g., the single cancer-specific CD8+ epitope comprises an amino acid sequence with 90-99% identity to an amino acid sequence as set forth in any of the SEQ ID NOs: 1-6.
- the single epitope e.g., the single T cell epitope, e.g., the single cancer-specific CD4+ and/or CD8+ epitope, e.g., the single cancer-specific CD8+ epitope comprises an amino acid sequence 1, 2, or at most 3 amino acid mutations compared to an amino acid sequence as set forth in any of the SEQ ID NOs: 1-6.
- the single epitope e.g., the single T cell epitope, e.g., the single cancer-specific CD4+ and/or CD8+ epitope, e.g., the single cancer-specific CD8+ epitope comprises an amino acid sequence as set forth in any of the SEQ ID NOs: 7-12.
- the single epitope e.g., the single T cell epitope, e.g., the single cancer-specific CD4+ and/or CD8+ epitope, e.g., the single cancer-specific CD8+ epitope comprises an amino acid sequence with 90-99% identity to an amino acid sequence as set forth in any of the SEQ ID NOs: 7-12.
- the single epitope e.g., the single T cell epitope, e.g., the single cancer-specific CD4+ and/or CD8+ epitope, e.g., the single cancer-specific CD8+ epitope comprises an amino acid sequence 1, 2, or at most 3 amino acid mutations compared to an amino acid sequence as set forth in any of the SEQ ID NOs: 7-12.
- the single epitope e.g., the single T cell epitope, e.g., the single cancer-specific CD4+ and/or CD8+ epitope, e.g., the single cancer-specific CD8+ epitope comprises an amino acid sequence as set forth in any of the SEQ ID NOs: 13-18.
- the single epitope e.g., the single T cell epitope, e.g., the single cancer-specific CD4+ and/or CD8+ epitope, e.g., the single cancer-specific CD8+ epitope comprises an amino acid sequence with 90-99% identity to an amino acid sequence as set forth in any of the SEQ ID NOs: 13-18.
- the single epitope e.g., the single T cell epitope, e.g., the single cancer-specific CD4+ and/or CD8+ epitope, e.g., the single cancer-specific CD8+ epitope comprises an amino acid sequence 1, 2, or at most 3 amino acid mutations compared to an amino acid sequence as set forth in any of the SEQ ID NOs: 13-18.
- overexpressed antigens can have lower expression levels in normal tissues and high expression levels in tumors.
- the single epitope e.g., the single T cell epitope, e.g., the single cancer-specific CD8+ and/or CD4+ epitope, e.g., the single cancer-specific CD8+ epitope comprises an amino acid sequence as set forth in SEQ ID NO: 1.
- the epitope e.g., the T cell epitope, e.g., the single cancer-specific CD8+ and/or CD4+ epitope, e.g., the cancer-specific CD8+ epitope comprises an amino acid sequence with 90-99% identity to the amino acid sequence of the epitope as set forth in SEQ ID NO: 1.
- the epitope, e.g., the T cell epitope, e.g., the single cancer-specific CD8+ and/or CD4+ epitope, e.g., the cancer-specific CD8+ epitope comprises an amino acid sequence as set forth in SEQ ID NO: 2.
- the epitope e.g., the T cell epitope, e.g., the single cancer-specific CD8+ and/or CD4+ epitope, e.g., the cancer-specific CD8+ epitope comprises an amino acid sequence with 90-99% identity to the amino acid sequence of the epitope as set forth in SEQ ID NO: 2.
- the epitope, e.g., the T cell epitope, e.g., the single cancer-specific CD8+ and/or CD4+ epitope, e.g., the cancer-specific CD8+ epitope comprises an amino acid sequence as set forth in SEQ ID NO: 3.
- the epitope e.g., the T cell epitope, e.g., the single cancer-specific CD8+ and/or CD4+ epitope, e.g., the cancer-specific CD8+ epitope comprises an amino acid sequence with 90-99% identity to the amino acid sequence of the epitope as set forth in SEQ ID NO: 3.
- the epitope, e.g., the T cell epitope, e.g., the single cancer-specific CD8+ and/or CD4+ epitope, e.g., the cancerspecific CD8+ epitope comprises an amino acid sequence as set forth in SEQ ID NO: 4.
- the epitope e.g., the T cell epitope, e.g., the single cancer-specific CD8+ and/or CD4+ epitope, e.g., the cancer-specific CD8+ epitope comprises an amino acid sequence with 90-99% identity to the amino acid sequence of the epitope as set forth in SEQ ID NO: 4.
- the epitope, e.g., the T cell epitope, e.g., the single cancer-specific CD8+ and/or CD4+ epitope, e.g., the cancer-specific CD8+ epitope comprises an amino acid sequence as set forth in SEQ ID NO: 5.
- the epitope e.g., the T cell epitope, e.g., the single cancer-specific CD8+ and/or CD4+ epitope, e.g., the cancer-specific CD8+ epitope comprises an amino acid sequence with 90-99% identity to the amino acid sequence of the epitope as set forth in SEQ ID NO: 5.
- the epitope, e.g., the T cell epitope, e.g., the single cancer-specific CD8+ and/or CD4+ epitope, e.g., the cancer-specific CD8+ epitope comprises an amino acid sequence as set forth in SEQ ID NO: 6.
- the epitope e.g., the T cell epitope, e.g., the single cancer-specific CD8+ and/or CD4+ epitope, e.g., the cancer-specific CD8+ epitope comprises an amino acid sequence with 90-99% identity to the amino acid sequence of the epitope as set forth in SEQ ID NO: 6.
- the single epitope e.g., the single T cell epitope, e.g., the single cancer-specific CD8+ and/or CD4+ epitope, e.g., the single cancer-specific CD8+ epitope comprises an amino acid sequence as set forth in SEQ ID NO: 7.
- the epitope e.g., the T cell epitope, e.g., the single cancer-specific CD8+ and/or CD4+ epitope, e.g., the cancer-specific CD8+ epitope comprises an amino acid sequence with 90-99% identity to the amino acid sequence of the epitope as set forth in SEQ ID NO: 7.
- the epitope, e.g., the T cell epitope, e.g., the single cancer-specific CD8+ and/or CD4+ epitope, e.g., the cancer-specific CD8+ epitope comprises an amino acid sequence as set forth in SEQ ID NO: 8.
- the epitope e.g., the T cell epitope, e.g., the single cancer-specific CD8+ and/or CD4+ epitope, e.g., the cancer-specific CD8+ epitope comprises an amino acid sequence with 90-99% identity to the amino acid sequence of the epitope as set forth in SEQ ID NO: 8.
- the epitope, e.g., the T cell epitope, e.g., the single cancer-specific CD8+ and/or CD4+ epitope, e.g., the cancer-specific CD8+ epitope comprises an amino acid sequence as set forth in SEQ ID NO: 9.
- the epitope e.g., the T cell epitope, e.g., the single cancer-specific CD8+ and/or CD4+ epitope, e.g., the cancer-specific CD8+ epitope comprises an amino acid sequence with 90-99% identity to the amino acid sequence of the epitope as set forth in SEQ ID NO: 9.
- the epitope, e.g., the T cell epitope, e.g., the single cancer-specific CD8+ and/or CD4+ epitope, e.g., the cancerspecific CD8+ epitope comprises an amino acid sequence as set forth in SEQ ID NO: 10.
- the epitope e.g., the T cell epitope, e.g., the single cancer-specific CD8+ and/or CD4+ epitope, e.g., the cancer-specific CD8+ epitope comprises an amino acid sequence with 90-99% identity to the amino acid sequence of the epitope as set forth in SEQ ID NO: 10.
- the epitope, e.g., the T cell epitope, e.g., the single cancer-specific CD8+ and/or CD4+ epitope, e.g., the cancer-specific CD8+ epitope comprises an amino acid sequence as set forth in SEQ ID NO: 11.
- the epitope e.g., the T cell epitope, e.g., the single cancer-specific CD8+ and/or CD4+ epitope, e.g., the cancer-specific CD8+ epitope comprises an amino acid sequence with 90-99% identity to the amino acid sequence of the epitope as set forth in SEQ ID NO: 11.
- the epitope, e.g., the T cell epitope, e.g., the single cancer-specific CD8+ and/or CD4+ epitope, e.g., the cancer-specific CD8+ epitope comprises an amino acid sequence as set forth in SEQ ID NO: 12.
- the epitope e.g., the T cell epitope, e.g., the single cancer-specific CD8+ and/or CD4+ epitope, e.g., the cancer-specific CD8+ epitope comprises an amino acid sequence with 90-99% identity to the amino acid sequence of the epitope as set forth in SEQ ID NO: 12.
- the single epitope e.g., the single T cell epitope, e.g., the single cancer-specific CD8+ and/or CD4+ epitope, e.g., the single cancer-specific CD8+ epitope comprises an amino acid sequence as set forth in SEQ ID NO: 13.
- the epitope e.g., the T cell epitope, e.g., the single cancer-specific CD8+ and/or CD4+ epitope, e.g., the cancer-specific CD8+ epitope comprises an amino acid sequence with 90-99% identity to the amino acid sequence of the epitope as set forth in SEQ ID NO: 13.
- the epitope, e.g., the T cell epitope, e.g., the single cancer-specific CD8+ and/or CD4+ epitope, e.g., the cancer-specific CD8+ epitope comprises an amino acid sequence as set forth in SEQ ID NO: 14.
- the epitope e.g., the T cell epitope, e.g., the single cancer-specific CD8+ and/or CD4+ epitope, e.g., the cancer-specific CD8+ epitope comprises an amino acid sequence with 90-99% identity to the amino acid sequence of the epitope as set forth in SEQ ID NO: 14.
- the epitope, e.g., the T cell epitope, e.g., the single cancerspecific CD8+ and/or CD4+ epitope, e.g., the cancer-specific CD8+ epitope comprises an amino acid sequence as set forth in SEQ ID NO: 15.
- the epitope e.g., the T cell epitope, e.g., the single cancer-specific CD8+ and/or CD4+ epitope, e.g., the cancer-specific CD8+ epitope comprises an amino acid sequence with 90-99% identity to the amino acid sequence of the epitope as set forth in SEQ ID NO: 15.
- the epitope, e.g., the T cell epitope, e.g., the single cancer-specific CD8+ and/or CD4+ epitope, e.g., the cancerspecific CD8+ epitope comprises an amino acid sequence as set forth in SEQ ID NO: 16.
- the epitope e.g., the T cell epitope, e.g., the single cancer-specific CD8+ and/or CD4+ epitope, e.g., the cancer-specific CD8+ epitope comprises an amino acid sequence with 90-99% identity to the amino acid sequence of the epitope as set forth in SEQ ID NO: 16.
- the epitope, e.g., the T cell epitope, e.g., the single cancer-specific CD8+ and/or CD4+ epitope, e.g., the cancer-specific CD8+ epitope comprises an amino acid sequence as set forth in SEQ ID NO: 17.
- the epitope e.g., the T cell epitope, e.g., the single cancer-specific CD8+ and/or CD4+ epitope, e.g., the cancer-specific CD8+ epitope comprises an amino acid sequence with 90-99% identity to the amino acid sequence of the epitope as set forth in SEQ ID NO: 17.
- the epitope, e.g., the T cell epitope, e.g., the single cancer-specific CD8+ and/or CD4+ epitope, e.g., the cancer-specific CD8+ epitope comprises an amino acid sequence as set forth in SEQ ID NO: 18.
- the epitope e.g., the T cell epitope, e.g., the single cancer-specific CD8+ and/or CD4+ epitope, e.g., the cancer-specific CD8+ epitope comprises an amino acid sequence with 90-99% identity to the amino acid sequence of the epitope as set forth in SEQ ID NO: 18.
- the recombinant polypeptide is from 8 to 100 amino acids in length. In some embodiments, the recombinant polypeptide is from 5 to 15 amino acids (e.g., 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, or 15) in length. In some embodiments, the recombinant polypeptide is from 8 to 12 amino acids in length.
- the recombinant polypeptide is from 9 to 10 amino acids in length. In some embodiments, the recombinant polypeptide is 8 amino acids in length. In some embodiments, the recombinant polypeptide is 9 amino acids in length. In some embodiments, the recombinant polypeptide is 10 amino acids in length. In some embodiments, the recombinant polypeptide is 11 amino acids in length. In some embodiments, the recombinant polypeptide is 12 amino acids in length.
- the recombinant polypeptide comprises more than one, e.g., 2, 3, 4, 5, 6, 7, 8, 9, 10, 15, 20, or 30 epitopes, e.g., T cell epitopes, e.g., cancer-specific CD8+ and/or CD4+ epitopes, e.g., cancer-specific CD8+ epitopes.
- the recombinant polypeptide comprises at least two epitopes, e.g., at least two T cell epitopes, e.g., at least two cancer-specific CD8+ and/or CD4+ epitopes, e.g., at least two cancer-specific CD8+ epitopes.
- the epitopes are identical. In some embodiments, the epitopes are different. In a non-limiting example, in some embodiments, a recombinant polypeptide disclosed herein may comprise three epitopes e.g., T cell epitopes, e.g., cancer-specific CD8+ and/or CD4+ epitopes, e.g., cancer-specific CD8+ epitopes of which two are identical and one different.
- T cell epitopes e.g., cancer-specific CD8+ and/or CD4+ epitopes, e.g., cancer-specific CD8+ epitopes of which two are identical and one different.
- the first epitope e.g., the first T cell epitope, e.g., the first cancer-specific CD8+ and/or CD4+ epitope, e.g., the first cancer-specific CD8+ epitope comprises an amino acid sequence set forth in any of SEQ ID NOs: 1-35.
- the second epitope e.g., the second T cell epitope, e.g., the second cancer-specific CD8+ and/or CD4+ epitope, e.g., the second cancer-specific CD8+ epitope comprises an amino acid sequence set forth in any of SEQ ID NOs: 1-35.
- the third epitope e.g., the third T cell epitope, e.g., the third cancer-specific CD8+ and/or CD4+ epitope, e.g., the third cancer-specific CD8+ epitope comprises an amino acid sequence set forth in any of SEQ ID NOs: 1-35.
- the fourth epitope e.g., the fourth T cell epitope, e.g., the fourth cancer- specific CD8+ and/or CD4+ epitope, e.g., the fourth cancer-specific CD8+ epitope comprises an amino acid sequence set forth in any of SEQ ID NOs: 1-35.
- the fifth epitope e.g., the fifth T cell epitope, e.g., the fifth cancer-specific CD8+ and/or CD4+ epitope, e.g., the fifth cancerspecific CD8+ epitope comprises an amino acid sequence set forth in any of SEQ ID NOs: 1-35.
- the sixth epitope e.g., the sixth T cell epitope, e.g., the sixth cancerspecific CD8+ and/or CD4+ epitope, e.g., the sixth cancer-specific CD8+ epitope comprises an amino acid sequence set forth in any of SEQ ID NOs: 1-35.
- the seventh epitope e.g., the seventh T cell epitope, e.g., the seventh cancer-specific CD8+ and/or CD4+ epitope, e.g., the seventh cancer-specific CD8+ epitope comprises an amino acid sequence set forth in any of SEQ ID NOs: 1-35.
- the eighth epitope e.g., the eighth T cell epitope, e.g., the eighth cancer-specific CD8+ and/or CD4+ epitope, e.g., the eighth cancerspecific CD8+ epitope comprises an amino acid sequence set forth in any of SEQ ID NOs: 1-35.
- the ninth epitope e.g., the ninth T cell epitope, e.g., the ninth cancerspecific CD8+ and/or CD4+ epitope, e.g., the ninth cancer-specific CD8+ epitope comprises an amino acid sequence set forth in any of SEQ ID NOs: 1-35.
- the tenth epitope e.g., the tenth T cell epitope, e.g., the tenth cancer-specific CD8+ and/or CD4+ epitope, e.g., the tenth cancer-specific CD8+ epitope comprises an amino acid sequence set forth in any of SEQ ID NOs: 1-35.
- the epitope e.g., the T cell epitope, e.g., the cancer-specific CD8+ and/or CD4+ epitope, e.g., the cancer-specific CD8+ epitope is derived from a tumor associated antigen (TAA).
- TAA tumor associated antigen
- a TAA is an antigenic product produced by a cancer and it provides a biomarker for targeted identification of a tumor.
- TAAs can be broadly categorized into aberrantly expressed self-antigens, mutated self-antigens and tumor specific antigens. As such, the TAA may be upregulated or over-expressed in the cancer cell.
- the TAA may be mutated within the cancer cell.
- the TAA may be specific for the cancer cell and only expressed within the cancer cell, this may also be referred to as a tumor specific antigen.
- the TAA may be overexpressed antigens that have lower expression levels in normal tissues and high expression levels in tumors.
- the TAA is associated with aggressive tumor behavior and/or show cancer-restricted expression. In some embodiments, the TAA enhances a CD8+ T cell immune response.
- the tumor-associated antigen is a tumor specific antigen.
- the single epitope e.g., the single T cell epitope, e.g., the single cancerspecific CD8+ epitope is a cancer testis antigen, e.g., a cancer testis antigen that is NY-ESO-1 or a member of the MAGE-A family. In some embodiments, the single epitope, e.g., the single T cell epitope, e.g., the single cancer-specific CD8+ epitope is an endogenous retroviral protein.
- the TAA is associated with aggressive tumor behavior and/or show cancer-restricted expression. In some embodiments, the TAA enhances a CD4+ T cell immune response.
- the tumor-associated antigen (TAA) is a tumor specific antigen.
- the single epitope, e.g., the single T cell epitope, e.g., the single cancerspecific CD4+ epitope is a cancer testis antigen, e.g., a cancer testis antigen that is NY-ESO-1 or a member of the MAGE-A family.
- the single epitope e.g., the single T cell epitope, e.g., the single cancer-specific CD4+ epitope is an endogenous retroviral protein.
- the single epitope e.g., the single T cell epitope, e.g., the single cancer-specific CD8+ and/or CD4+ epitope, e.g., the single cancer-specific CD8+ epitope is mutated in a cancer cell.
- the single epitope e.g., the single T cell epitope, e.g., the single cancer-specific CD8+ and/or CD4+ epitope, e.g., the single cancer-specific CD8+ epitope is overexpressed in a cancer cell.
- the single epitope e.g., the single T cell epitope, e.g., the single cancer-specific CD8+ and/or CD4+ epitope, e.g., the single cancer-specific CD8+ epitope is or comprises a non-coding tumor specific epitope.
- non-coding tumor specific epitope refers to a peptide found on a cancer cell, wherein the peptide is derived from a nucleotide sequence that is epigenetically suppressed in healthy cells. These peptide sequences are aberrantly expressed within tumor cells.
- the single epitope e.g., the single T cell epitope, e.g., the single cancer-specific CD8+ and/or CD4+ epitope, e.g., the single cancer-specific CD8+ epitope is not a cryptic epitope.
- a “cryptic epitope” refers to an epitope which is not immunogenic in immunocompetent individuals.
- the single epitope, e.g., the single T cell epitope, e.g., the single cancer-specific CD8+ and/or CD4+ epitope, e.g., the single cancer-specific CD8+ epitope is a cryptic epitope.
- the single epitope e.g., the single T cell epitope, e.g., the single cancer-specific CD8+ and/or CD4+ epitope, e.g., the single cancer-specific CD8+ epitope can be a viral epitope optionally associated with a virally driven cancer.
- the virally driven cancer may be a cancer caused by HPV (human papilloma virus), HTLV (human T-lymphotropic virus), or EBV (Epstein Barr virus).
- the single epitope e.g., the single T cell epitope, e.g., the single cancer-specific CD8+ epitope is or is derived from a tumor associated antigen selected from the group comprising: TRP-1, CEA, TAG-72, 9D7, Ep-CAM, EphA3, telomerase, mesothelin, SAP- 1 Mel an- ATM ART- 1, tyrosinase, CLPP, cyclin-Al, cyclin-Bl MAGE- Al, MAGE-CI, MAGE- 02, SSX2, XAGElb/GAGED2a, CD45, glypican-3, IGF2B3, kallikrein-4, KIF20A, lengsin, meloe, MUC5AC, survivin, PRAME, SSX-2, NY-ESO-1/LAGE1, gp70, MC1R, TRP-1/-2, 0- catenin, BRCA1/2
- a tumor associated antigen
- the single epitope e.g., the single T cell epitope, e.g., the single cancer-specific CD4+ epitope is or is derived from a tumor associated antigen selected from the group comprising: EBNA2, TARP, EBV LMP1, STEAP, WT1, HTLV-1 env, HER2/neu, MAGE- A3, BRAF-V600E, NY-ESO-1, or gplOO.
- the single epitope e.g., the single T cell epitope, e.g., the single cancer-specific CD8+ and/or CD4+ epitope, e.g., the single cancer-specific CD8+ epitope is an epitope associated with colorectal cancer, prostate cancer, esophageal cancer, liver cancer, renal cancer, lung cancer, bladder cancer, breast cancer, pancreatic cancer, brain cancer, hepatocellular cancer, lymphoma, leukaemia, gastric cancer, cervical cancer, ovarian cancer, thyroid cancer, melanoma, carcinoma, head and neck cancer, skin cancer, nasopharyngeal cancer, Epstein Barr driven cancers, Human Papilloma virus driven cancers or soft tissue sarcoma.
- the cancer is a primary cancer.
- the cancer is a relapsed and/or a refractory cancer.
- the single epitope e.g., the single T cell epitope, e.g., the single cancer-specific CD8+ and/or CD4+ epitope, e.g., the single cancer-specific CD8+ epitope is an esophageal cancer-specific CD8+ T cell epitope.
- the single epitope e.g., the single T cell epitope, e.g., the single cancer-specific CD8+ and/or CD4+ epitope, e.g., the single cancer-specific CD8+ epitope is a colorectal cancer-specific CD8+ T cell epitope.
- the single epitope e.g., the single T cell epitope, e.g., the single cancer-specific CD8+ and/or CD4+ epitope, e.g., the single cancer-specific CD8+ epitope is a prostate cancerspecific CD8+ T cell epitope.
- the single epitope, e.g., the single T cell epitope, e.g., the single cancer-specific CD8+ and/or CD4+ epitope, e.g., the single cancerspecific CD8+ epitope is a liver cancer-specific CD8+ T cell epitope.
- the single epitope e.g., the single T cell epitope, e.g., the single cancer-specific CD8+ and/or CD4+ epitope, e.g., the single cancer-specific CD8+ epitope is a renal cancer-specific CD8+ T cell epitope.
- the single epitope, e.g., the single T cell epitope, e.g., the single cancer-specific CD8+ and/or CD4+ epitope, e.g., the single cancer-specific CD8+ epitope is a breast cancer-specific CD8+ T cell epitope.
- the single epitope e.g., the single T cell epitope, e.g., the single cancer-specific CD8+ and/or CD4+ epitope, e.g., the single cancer-specific CD8+ epitope is a bladder cancer-specific CD8+ T cell epitope.
- the single epitope, e.g., the single T cell epitope, e.g., the single cancer-specific CD8+ and/or CD4+ epitope, e.g., the single cancer-specific CD8+ epitope is a pancreatic cancerspecific CD8+ T cell epitope.
- the single epitope e.g., the single T cell epitope, e.g., the single cancer-specific CD8+ and/or CD4+ epitope, e.g., the single cancerspecific CD8+ epitope is a lung cancer-specific CD8+ T cell epitope.
- the single epitope, e.g., the single T cell epitope, e.g., the single cancer-specific CD8+ and/or CD4+ epitope, e.g., the single cancer-specific CD8+ epitope is a brain cancer-specific CD8+ T cell epitope.
- the single epitope e.g., the single T cell epitope, e.g., the single cancer-specific CD8+ and/or CD4+ epitope, e.g., the single cancer-specific CD8+ epitope is a hepatocellular cancer-specific CD8+ T cell epitope.
- the single epitope e.g., the single T cell epitope, e.g., the single cancer-specific CD8+ and/or CD4+ epitope, e.g., the single cancer-specific CD8+ epitope is a gastric cancer-specific CD8+ T cell epitope.
- the single epitope e.g., the single T cell epitope, e.g., the single cancerspecific CD8+ and/or CD4+ epitope, e.g., the single cancer-specific CD8+ epitope is a cervical cancer-specific CD8+ T cell epitope.
- the single epitope, e.g., the single T cell epitope, e.g., the single cancer-specific CD8+ and/or CD4+ epitope, e.g., the single cancerspecific CD8+ epitope is an ovarian cancer-specific CD8+ T cell epitope.
- the single epitope e.g., the single T cell epitope, e.g., the single cancer-specific CD8+ and/or CD4+ epitope, e.g., the single cancer-specific CD8+ epitope is a thyroid cancer-specific CD8+ T cell epitope.
- the single epitope, e.g., the single T cell epitope, e.g., the single cancer-specific CD8+ and/or CD4+ epitope, e.g., the single cancer-specific CD8+ epitope is a CD8+ T cell epitope specific for melanoma.
- the single epitope e.g., the single T cell epitope, e.g., the single cancer-specific CD8+ and/or CD4+ epitope, e.g., the single cancer-specific CD8+ epitope is a CD8+ T cell epitope specific for lymphoma.
- the single epitope, e.g., the single T cell epitope, e.g., the single cancer-specific CD8+ and/or CD4+ epitope, e.g., the single cancer-specific CD8+ epitope is a CD8+ T cell epitope specific for leukemia.
- the single epitope e.g., the single T cell epitope, e.g., the single cancer-specific CD8+ and/or CD4+ epitope, e.g., the single cancerspecific CD8+ epitope specific for carcinoma.
- the single epitope, e.g., the single T cell epitope, e.g., the single cancer-specific CD8+ and/or CD4+ epitope, e.g., the single cancer-specific CD8+ epitope is a CD8+ T cell epitope specific for head and neck cancer.
- the single epitope e.g., the single T cell epitope, e.g., the single cancerspecific CD8+ and/or CD4+ epitope, e.g., the single cancer-specific CD8+ epitope is a CD8+ T cell epitope specific for skin cancer.
- the single epitope, e.g., the single T cell epitope, e.g., the single cancer-specific CD8+ and/or CD4+ epitope, e.g., the single cancerspecific CD8+ epitope is a CD8+ T cell epitope specific for soft tissue sarcoma.
- the single epitope e.g., the single T cell epitope, e.g., the single cancer-specific CD8+ and/or CD4+ epitope, e.g., the single cancer-specific CD8+ epitope is a CD8+ T cell epitope specific for nasopharyngeal cancer.
- the single epitope e.g., the single T cell epitope, e.g., the single cancer-specific CD8+ and/or CD4+ epitope, e.g., the single cancer-specific CD8+ epitope may be a private epitope.
- the term “private epitope” refers to an epitope which is found exclusively on a single antigen in a cancer of a single person.
- the single epitope, e.g., the single T cell epitope, e.g., the single cancer-specific CD8+ and/or CD4+ epitope, e.g., the single cancer-specific CD8+ epitope may be a public epitope.
- the term “public epitope” refers to an epitope that is found on a cancer of two or more people.
- the recombinant polypeptide comprising the single epitope e.g., the single T cell epitope, e.g., the single cancer-specific CD8+ and/or CD4+ epitope, e.g., the single cancer-specific CD8+ epitope is capable of inducing an epitope-specific T cell response.
- the recombinant polypeptide comprising the single epitope, e.g., the single T cell epitope, e.g., the single cancer-specific CD8+ and/or CD4+ epitope, e.g., the single cancer-specific CD8+ epitope is capable of inducing an inflating memory CD8+ T cell response.
- the recombinant polypeptide comprising the single epitope e.g., the single T cell epitope, e.g., the single cancer-specific CD8+ and/or CD4+ epitope, e.g., the single cancer-specific CD8+ epitope
- the single epitope e.g., the single T cell epitope, e.g., the single cancer-specific CD8+ and/or CD4+ epitope, e.g., the single cancer-specific CD8+ epitope
- APCs antigen presenting cells
- the single epitope e.g., the single T cell epitope, e.g., the single cancer-specific CD8+ and/or CD4+ epitope, e.g., the single cancer-specific CD8+ epitope may be a neoepitope.
- the term “neoepitope” refers to epitopes which have arisen through mutations within the tumor cells, in particular somatic or passenger mutations may lead to the production of a neoepitope.
- single epitope e.g., the single T cell epitope, e.g., the single cancer-specific CD8+ and/or CD4+ epitope, e.g., the single cancerspecific CD8+ epitope is not a neoepitope.
- the recombinant polypeptide can be a glycoconjugate protein.
- the recombinant polypeptide can be a ubiquitinated protein.
- the recombinant polypeptide can be a phosphorylated protein.
- the recombinant polypeptide can be an acetylated protein.
- the recombinant polypeptide can be a methylated protein. In some embodiments, the recombinant polypeptide comprises a signal peptide. “Signal peptide” as used herein refers to an amino acid sequence that can be linked at the amino terminus of recombinant polypeptide disclosed herein. Signal peptides typically direct localization of a protein.
- the disclosure provides a polynucleotide encoding a recombinant polypeptide comprising a single epitope, e.g., a single T cell epitope, e.g., a single cancer-specific CD8+ and/or CD4+ epitope, e.g., a single cancer-specific CD8+ epitope described herein.
- a single epitope e.g., a single T cell epitope, e.g., a single cancer-specific CD8+ and/or CD4+ epitope, e.g., a single cancer-specific CD8+ epitope described herein.
- a polynucleotide encodes a recombinant polypeptide comprising a single epitope, e.g., a single T cell epitope, e.g., a single cancer-specific CD8+ and/or CD4+ epitope, e.g., a single cancer-specific CD8+ epitope comprising an amino acid sequence as set forth in any of SEQ ID NOs: 1-35.
- a polynucleotide encodes a recombinant polypeptide comprising a single epitope, e.g., a single T cell epitope, e.g., a single cancer-specific CD8+ and/or CD4+ epitope, e.g., a single cancer-specific CD8+ epitope comprising an amino acid sequence as set forth in any of SEQ ID NOs: 1-13.
- a polynucleotide encodes a recombinant polypeptide comprising a single epitope, e.g., a single T cell epitope, e.g., a single cancer-specific CD8+ and/or CD4+ epitope, e.g., a single cancer-specific CD8+ epitope comprising an amino acid sequence as set forth in any of SEQ ID NOs: 1-6.
- a polynucleotide encodes a recombinant polypeptide comprising a single epitope, e.g., a single T cell epitope, e.g., a single cancer-specific CD8+ and/or CD4+ epitope, e.g., a single cancer-specific CD8+ epitope comprising an amino acid sequence as set forth in any of SEQ ID NOs: 7-12.
- a polynucleotide encodes a recombinant polypeptide comprising a single epitope, e.g., a single T cell epitope, e.g., a single cancer-specific CD8+ and/or CD4+ epitope, e.g., a single cancer-specific CD8+ epitope comprising an amino acid sequence as set forth in any of SEQ ID NOs: 13-18.
- Polynucleotides includes, for example, genomic DNA, cDNA, RNA, e.g., mRNA, and DNA-RNA hybrid molecules. Polynucleotides can be naturally occurring, recombinant, or synthetic. In addition, polynucleotides can be single-stranded, double-stranded or triple-stranded. In certain embodiments, polynucleotides can be modified. In the case of a double-stranded polymer, “nucleic acid” can refer to either or both strands of the molecule. In some embodiments, the polynucleotide is provided as DNA. In some embodiments, the polynucleotide is provided as RNA, e.g., an mRNA.
- a polynucleotide disclosed herein comprises a nucleic acid sequence as set forth in any of SEQ ID NOs: 52-86. In some embodiments, a polynucleotide disclosed herein comprises a nucleic acid sequence as shown in Table 2.
- the polynucleotides disclosed herein can be codon optimized, usage bias has been reported for numerous organisms, from viruses to eukaryotes. Since the genetic code is degenerate (i.e., each amino acid can be coded by on average three different codons), the DNA sequence can be modified by synonymous nucleotide substitutions without altering the amino acid sequence of the encoded protein. Such synonymous codon optimization has been performed for the purpose of optimizing expression in a desired host, as described in the scientific literature and in patent documents. See U.S. Pat. Nos. 5,786,464 and 6,114,14. In some embodiments, the nucleic acid described herein can be modified to improve cloning efficiency.
- nucleic acids described herein are subjected to codon optimization to increase the efficiency of gene expression, e.g., SEQ ID NOs 87-121. are subjected to codon optimization.
- polypeptide disclosed herein are encoded by polynucleotides whose sequence has been codon optimized for expression in a mammalian cell, e.g., expressional in a human cell. Exemplary codon optimized sequences are disclosed in Table 3.
- polypeptides encoded by a codon optimized nucleotide have increased expression in a mammalian cell, e.g., a human cell compared to a polypeptide that is encoded by a non-codon optimized polynucleotide.
- a polypeptide comprising an amino acid sequence as set forth SEQ ID NO: 1 can be encoded by a polynucleotide having a sequence as set forth in SEQ ID NO: 52 or 87.
- a polypeptide comprising an amino acid sequence as set forth SEQ ID NO: 2 can be encoded by a polynucleotide having a sequence as set forth in SEQ ID NO: 53 or 88.
- a polypeptide comprising an amino acid sequence as set forth SEQ ID NO: 3 can be encoded by a polynucleotide having a sequence as set forth in SEQ ID NO: 54 or 89.
- a polypeptide comprising an amino acid sequence as set forth SEQ ID NO: 4 can be encoded by a polynucleotide having a sequence as set forth in SEQ ID NO: 55 or 90.
- a polypeptide comprising an amino acid sequence as set forth SEQ ID NO: 5 can be encoded by a polynucleotide having a sequence as set forth in SEQ ID NO: 56 or 91.
- a polypeptide comprising an amino acid sequence as set forth SEQ ID NO: 6 can be encoded by a polynucleotide having a sequence as set forth in SEQ ID NO: 57 or 92.
- a polypeptide comprising an amino acid sequence as set forth SEQ ID NO: 7 can be encoded by a polynucleotide having a sequence as set forth in SEQ ID NO: 58 or 93.
- a polypeptide comprising an amino acid sequence as set forth SEQ ID NO: 8 can be encoded by a polynucleotide having a sequence as set forth in SEQ ID NO: 59 or 94.
- a polypeptide comprising an amino acid sequence as set forth SEQ ID NO: 9 can be encoded by a polynucleotide having a sequence as set forth in SEQ ID NO: 60 or 95.
- a polypeptide comprising an amino acid sequence as set forth SEQ ID NO: 10 can be encoded by a polynucleotide having a sequence as set forth in SEQ ID NO: 61 or 96.
- a polypeptide comprising an amino acid sequence as set forth SEQ ID NO: 11 can be encoded by a polynucleotide having a sequence as set forth in SEQ ID NO: 62 or 97.
- a polypeptide comprising an amino acid sequence as set forth SEQ ID NO: 12 can be encoded by a polynucleotide having a sequence as set forth in SEQ ID NO: 63 or 98.
- a polypeptide comprising an amino acid sequence as set forth SEQ ID NO: 13 can be encoded by a polynucleotide having a sequence as set forth in SEQ ID NO: 64 or 99.
- a polypeptide comprising an amino acid sequence as set forth SEQ ID NO: 14 can be encoded by a polynucleotide having a sequence as set forth in SEQ ID NO: 65 or 100.
- a polypeptide comprising an amino acid sequence as set forth SEQ ID NO: 15 can be encoded by a polynucleotide having a sequence as set forth in SEQ ID NO: 66 or 101.
- a polypeptide comprising an amino acid sequence as set forth SEQ ID NO: 16 can be encoded by a polynucleotide having a sequence as set forth in SEQ ID NO: 67 or 102.
- a polypeptide comprising an amino acid sequence as set forth SEQ ID NO: 17 can be encoded by a polynucleotide having a sequence as set forth in SEQ ID NO: 68 or 103.
- a polypeptide comprising an amino acid sequence as set forth SEQ ID NO: 18 can be encoded by a polynucleotide having a sequence as set forth in SEQ ID NO: 69 or 104.
- a polypeptide comprising an amino acid sequence as set forth SEQ ID NO: 19 can be encoded by a polynucleotide having a sequence as set forth in SEQ ID NO: 70 or 105.
- a polypeptide comprising an amino acid sequence as set forth SEQ ID NO: 20 can be encoded by a polynucleotide having a sequence as set forth in SEQ ID NO: 71 or 106.
- a polypeptide comprising an amino acid sequence as set forth SEQ ID NO: 21 can be encoded by a polynucleotide having a sequence as set forth in SEQ ID NO: 72 or 107.
- a polypeptide comprising an amino acid sequence as set forth SEQ ID NO: 22 can be encoded by a polynucleotide having a sequence as set forth in SEQ ID NO: 73 or 108.
- a polypeptide comprising an amino acid sequence as set forth SEQ ID NO: 23 can be encoded by a polynucleotide having a sequence as set forth in SEQ ID NO: 74 or 109.
- a polypeptide comprising an amino acid sequence as set forth SEQ ID NO: 24 can be encoded by a polynucleotide having a sequence as set forth in SEQ ID NO: 75 or 110. .
- a polypeptide comprising an amino acid sequence as set forth SEQ ID NO: 25 can be encoded by a polynucleotide having a sequence as set forth in SEQ ID NO: 76 or 111.
- a polypeptide comprising an amino acid sequence as set forth SEQ ID NO: 26 can be encoded by a polynucleotide having a sequence as set forth in SEQ ID NO: 77 or 112.
- a polypeptide comprising an amino acid sequence as set forth SEQ ID NO: 27 can be encoded by a polynucleotide having a sequence as set forth in SEQ ID NO: 78 or 113. .
- a polypeptide comprising an amino acid sequence as set forth SEQ ID NO: 28 can be encoded by a polynucleotide having a sequence as set forth in SEQ ID NO: 79 or 114. .
- a polypeptide comprising an amino acid sequence as set forth SEQ ID NO: 29 can be encoded by a polynucleotide having a sequence as set forth in SEQ ID NO: 80 or 115.
- a polypeptide comprising an amino acid sequence as set forth SEQ ID NO: 30 can be encoded by a polynucleotide having a sequence as set forth in SEQ ID NO: 81 or 116.
- a polypeptide comprising an amino acid sequence as set forth SEQ ID NO: 31 can be encoded by a polynucleotide having a sequence as set forth in SEQ ID NO: 82 or 117.
- a polypeptide comprising an amino acid sequence as set forth SEQ ID NO: 32 can be encoded by a polynucleotide having a sequence as set forth in SEQ ID NO: 83 or 118.
- a polypeptide comprising an amino acid sequence as set forth SEQ ID NO: 33 can be encoded by a polynucleotide having a sequence as set forth in SEQ ID NO: 84 or 119.
- a polypeptide comprising an amino acid sequence as set forth SEQ ID NO: 34 can be encoded by a polynucleotide having a sequence as set forth in SEQ ID NO: 85 or 120.
- a polypeptide comprising an amino acid sequence as set forth SEQ ID NO: 35 can be encoded by a polynucleotide having a sequence as set forth in SEQ ID NO: 86 or 121.
- a polynucleotide disclosed herein can encode multiple epitopes, e.g., 2, 3, 4, 5, 6, 7, 8, 9, or 10 epitopes. In some embodiments, the polynucleotide encodes multiple epitopes as discrete peptide epitopes. In some embodiments, the polynucleotide encodes multiple epitopes as poly epitopic peptides. In some embodiments, the epitopes are identical. In some embodiments, the epitopes are different. In some embodiments, a polynucleotide may comprise a sequence encoding at least two or more epitopes described herein, of which both epitopes are the same epitopes.
- a polynucleotide may comprise a sequence encoding at least two or more epitopes described herein, of which both epitopes are different epitopes.
- a polynucleotide disclosed herein can encode three epitopes e.g., T cell epitopes, e.g., cancer-specific CD8+ and/or CD4+ epitopes, e.g., cancer-specific CD8+ epitopes of which two are the same epitopes and one is a different epitope.
- the polynucleotide comprises a nucleotide sequence that encodes spacer amino acid residues between the first and the second epitope.
- a nucleic acid comprises regulatory sequences from a plasmid.
- the nucleic acid sequence can include, for example, one or more of a promoter sequence a selection marker sequence, or a locus-targeting sequence.
- An example of a promoter that is capable of expressing a transgene in a mammalian T cell is a EFla promoter (SEQ ID NO: 122).
- the native EFla promoter drives expression of the alpha subunit of the elongation factor-1 complex, which is responsible for the enzymatic delivery of aminoacyl tRNAs to the ribosome.
- the polynucleotide comprises an EFla promoter.
- CMV immediate early cytomegalovirus
- This promoter sequence is a strong constitutive promoter sequence capable of driving high levels of expression of any polynucleotide sequence operatively linked thereto.
- the polynucleotide comprises a CMV promoter.
- the CMV promoter comprises a sequence with 80-100% sequence identity as that set forth in SEQ ID NO: 36.
- the polynucleotide of the present disclosure may comprise a promoter selected from the group consisting of, but not limited to, a simian virus 40 (SV40) early promoter, a mouse mammary tumor virus (MMTV), a human immunodeficiency virus (HIV) long terminal repeat (LTR) promoter, a MoMuLV promoter, an avian leukemia virus promoter, an Epstein-Barr virus immediate early promoter, a Rous sarcoma virus (RSV) promoter, an actin promoter, a myosin promoter, an elongation factor-la promoter, a hemoglobin promoter, and a creatine kinase promoter.
- SV40 simian virus 40
- MMTV mouse mammary tumor virus
- HSV human immunodeficiency virus
- LTR long terminal repeat
- MoMuLV promoter avian leukemia virus promoter
- ESV Rous sarcoma virus
- actin promoter
- the polynucleotide comprises a sequence encoding a poly(A) tail. In some instances, the polynucleotide comprises a 3’ UTR sequence. In some instances, the polynucleotide comprises a 5’ UTR sequence.
- a polynucleotide disclosed herein comprises multiple smaller and discrete nucleotide sequences that are typically heterologous and exhibit different and measurable function(s), a promoter sequence, a translation initiating sequence, a start codon, a polyadenylation sequence, a stop codon, a nucleotide sequence encoding an epitope, e.g., a T cell epitope, e.g., a cancer-specific CD8+ and/or CD4+ epitope, e.g., a cancer-specific CD8+ epitope, e.g., an epitope comprising an amino acid sequence as set forth in any of SEQ ID NOs 1-35, and/or a linker encoding sequence.
- the polynucleotide is codon optimized, e.g., codon optimized for optimal expression in a mammalian cell, e.g., a human cell.
- the polynucleotide e.g., the RNA, e.g., the mRNA encoding the epitope, e.g., the T cell epitope, e.g., the cancer-specific CD8+ and/or CD4+ epitope, e.g., the cancer-specific CD8+ epitope is introduced into cells.
- in vitro transcribed RNA can be introduced to a cell as a form of transient transfection.
- the polynucleotide can include some or all of the 5’ and/or 3’ untranslated regions (UTRs).
- the polynucleotide can include exons and introns.
- the DNA to be used for PCR is a human nucleic acid sequence. In some embodiments, the DNA to be used for PCR is a human nucleic acid sequence including the 5’ and 3’ UTRs.
- the DNA can alternatively be an artificial DNA sequence that is not normally expressed in a naturally occurring organism.
- An exemplary artificial DNA sequence is one that contains portions of genes that are ligated together to form an open reading frame that encodes a fusion protein. The portions of DNA that are ligated together can be from a single organism or from more than one organism.
- the RNA preferably has 5’ and 3’ UTRs.
- the 5’ UTR is between one and 3,000 nucleotides in length.
- the length of 5’ and 3’ UTR sequences to be added to the coding region can be altered by different methods, including, but not limited to, designing primers for PCR that anneal to different regions of the UTRs. Using this approach, one of ordinary skill in the art can modify the 5’ and 3’ UTR lengths that can be used to achieve optimal translation efficiency following transfection of the transcribed RNA.
- the 5’ and 3’ UTRs can be the naturally occurring, endogenous 5’ and 3’ UTRs for the polynucleotide of interest.
- UTR sequences that are not endogenous to the polynucleotide of interest can be added by incorporating the UTR sequences into the forward and reverse primers or by any other modifications of the template.
- the use of UTR sequences that are not endogenous to the polynucleotide of interest can be useful for modifying the stability and/or translation efficiency of the RNA. For example, it is known that AU-rich elements in
- 3 ’UTR sequences can decrease the stability of mRNA. Therefore, 3’ UTRs can be selected or designed to increase the stability of the transcribed RNA based on properties of UTRs that are well known in the art.
- the 5’ UTR can contain the Kozak sequence of the endogenous nucleic acid.
- a consensus Kozak sequence can be redesigned by adding the 5’ UTR sequence.
- Kozak sequences can increase the efficiency of translation of some RNA transcripts.
- the 5’ UTR can be 5 ’UTR of an RNA virus whose RNA genome is stable in cells.
- various nucleotide analogues can be used in the 3’ or 5’ UTR to impede exonuclease degradation of the mRNA.
- the polynucleotide further comprises a promoter of transcription e.g., a T7 polymerase promoter.
- a promoter of transcription e.g., a T7 polymerase promoter.
- Other useful promoters include, but are not limited to, T3 and SP6 RNA polymerase promoters. Consensus nucleotide sequences for T7, T3 and SP6 promoters are known in the art.
- the polynucleotide e.g., the mRNA has both a cap on the 5’ end and a 3’ poly(A) tail which determine ribosome binding, initiation of translation and stability mRNA in the cell.
- the polynucleotide comprises a Poly (A) tail, e.g., a Poly(A) tails providing stability to the mRNA and/or reduce mRNA degradation.
- the poly(A) tail is between 100 and 5000 adenosines.
- the polynucleotide may comprise immunostimulatory sequences (e.g., ISSs or CpGs).
- the polynucleotide can also contain an internal ribosome entry site (IRES) sequence.
- IRES sequence may be any viral, chromosomal or artificially designed sequence which initiates cap-independent ribosome binding to mRNA and facilitates the initiation of translation. Any solutes suitable for cell electroporation, which can contain factors facilitating cellular permeability and viability such as sugars, peptides, lipids, proteins, antioxidants, and surfactants can be included.
- the polynucleotide of this disclosure can encode any recombinant polypeptide described herein.
- the polynucleotide can encode a recombinant polypeptide comprising a cancer-specific T cell epitope having a sequence identity of at least about 90-100% to SEQ ID NO: 1, SEQ ID NO: 2, SEQ ID NO: 3, SEQ ID NO: 4, SEQ ID NO: 5, SEQ ID NO: 6, SEQ ID NO: 7, SEQ ID NO: 8, SEQ ID NO: 9, SEQ ID NO: 10, SEQ ID NO: 11, SEQ ID NO: 12, SEQ ID NO: 13, SEQ ID NO: 14, SEQ ID NO: 15, SEQ ID NO: 16, SEQ ID NO: 17, SEQ ID NO: 18, SEQ ID NO: 19, SEQ ID NO: 20, SEQ ID NO: 21, SEQ ID NO: 22, SEQ ID NO: 23, SEQ ID NO: 24, SEQ ID NO: 25, SEQ ID NO: 26, SEQ ID NO: 27, SEQ ID NO: 28, SEQ ID NO:
- the polynucleotide can encode a recombinant polypeptide having at least about 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, or more amino acid residues of SEQ ID NO: 1, SEQ ID NO: 2, SEQ ID NO: 3, SEQ ID NO: 4, SEQ ID NO: 5, SEQ ID NO: 6, SEQ ID NO: 7, SEQ ID NO: 8, SEQ ID NO: 9, SEQ ID NO: 10, SEQ ID NO: 11, SEQ ID NO: 12, SEQ ID NO: 13, SEQ ID NO: 14, SEQ ID NO: 15, SEQ ID NO: 16, SEQ ID NO: 17, SEQ ID NO: 18, SEQ ID NO: 19, SEQ ID NO: 20, SEQ ID NO: 21, SEQ ID NO: 22, SEQ ID NO: 23, SEQ ID NO: 24, SEQ ID NO: 25, SEQ ID NO: 26, SEQ ID NO: 27, SEQ ID NO: 28, SEQ ID NO: 29, SEQ ID NO: 30, SEQ ID NO: 31, SEQ ID NO: 32, SEQ ID NO: 33, SEQ ID NO:
- the polynucleotide can encode a recombinant polypeptide having at least about 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, or more amino acid substitutions of SEQ ID NO: 1, SEQ ID NO: 2, SEQ ID NO: 3, SEQ ID NO: 4, SEQ ID NO: 5, SEQ ID NO: 6, SEQ ID NO: 7, SEQ ID NO: 8, SEQ ID NO: 9, SEQ ID NO: 10, SEQ ID NO: 11, SEQ ID NO: 12, SEQ ID NO: 13, SEQ ID NO: 14, SEQ ID NO: 15, SEQ ID NO: 16, SEQ ID NO: 17, SEQ ID NO: 18, SEQ ID NO: 19, SEQ ID NO: 20, SEQ ID NO: 21, SEQ ID NO: 22, SEQ ID NO: 23, SEQ ID NO: 24, SEQ ID NO: 25, SEQ ID NO: 26, SEQ ID NO: 27, SEQ ID NO: 28, SEQ ID NO: 29, SEQ ID NO: 30, SEQ ID NO: 31, SEQ ID NO: 32, SEQ ID NO: 33, SEQ ID NO:
- the polynucleotide encodes a recombinant polypeptide comprising a cancer-specific CD8+ T cell epitope that can bind to an HLA molecule e.g., an HLA-A allele, e.g., an HLA-B allele, e.g., an HLA-C allele.
- an HLA molecule e.g., an HLA-A allele, e.g., an HLA-B allele, e.g., an HLA-C allele.
- the HLA-A allele is an HLA-A*15 allele, (e.g., an HLA-A*15:01 allele), an HLA-A*02 allele (e.g., an HLA-A*02:01 allele, e.g., an HLA-A*02:05 allele), an HLA-A*03 allele (e.g., an HLA-A*03:01 allele,, an HLA-A* 11 allele (e.g., an HLA-A* 11 :01 allele), or an HLA-A*31 allele (e.g., an HLA-A*31 :01 allele).
- HLA-A*15 allele e.g., an HLA-A*15:01 allele
- an HLA-A*02 allele e.g., an HLA-A*02:01 allele, e.g., an HLA-A*02:05 allele
- an HLA-A*03 allele e.g
- the HLA-B allele is an HLA-B*07 allele (e.g., an HLA-B*07:02 allele), an HLA-B*08 allele (e.g., an HLA-B*08:01 allele), an HLA-B*15 allele (e.g., an HLA- B*15:01 allele), an HLA-B*18 allele (e.g., an HLA-B*18:01 allele), an HLA-B*35 allele (e.g., an HLA-B*35:01 allele, an HLA-B*35:03 allele), an HLA-B*40 allele (e.g., an HLA-B*40:01 allele, an HLA-B*40:02 allele), or an HLA-B*44 allele (e.g., an HLA-B*44:01 allele, e.g., an HLA-B*44:02 allele).
- HLA-B*07 allele e.g
- the HLA-C allele is an HLA-C*03 allele, (e.g. an HLA-C*03:04 allele), or an HLA-C*07 allele, (e.g., an HLA-C*07:01 allele, e.g., an HLA- C*07:02 allele).
- the nucleotide sequence encoding an epitope e.g., a single T cell epitope, e.g., a single cancer-specific CD8+ and/or CD4+ epitope, e.g., a single cancer-specific CD8+ epitope may comprise from approximately 12 to approximately 45 base pairs, e.g., approximately 15 to
- a polynucleotide disclosed herein can be a spherical nucleic acid (SNA).
- an SNA disclosed herein comprises a nanoparticle conjugated with a polynucleotide sequence disclosed herein.
- a SNA disclosed herein comprises an unilamellar liposome core.
- a SNA disclosed herein comprises one or more CpG oligonucleotides.
- an SNA disclosed herein comprises a polynucleotide, e.g., a polynucleotide comprising any of SEQ ID NOs: 52-121 encapsulated within the liposome core.
- a polynucleotide e.g., a polynucleotide comprising any of SEQ ID NOs: 52-121 is located on the surface of an SNA disclosed herein.
- a polynucleotide e.g., a polynucleotide comprising any of SEQ ID NOs: 52121 is chemically conjugated to the liposomal surface of an SNA disclosed herein.
- a polynucleotide, e.g., a polynucleotide comprising any of SEQ ID NOs: 52121 is hybridized to one or more CpG oligonucleotides and adsorbed to the liposome surface.
- an SNA disclosed herein can be a liposomal SNA.
- the disclosure provides a vector, e.g., a vector comprising a recombinant polypeptide described herein, a vector comprising a polynucleotide encoding a recombinant polypeptide described herein.
- the vector is a viral vector.
- the vector is a non-viral vector.
- a viral vector can be an adenovirus vector, an adeno-associated virus (AAV) vector (e.g., AAV type 5 and type 2), an alphavirus vectors (e.g., Venezuelan equine encephalitis virus (VEE), a Sindbis virus (SIN), semliki forest virus (SFV), and VEE-SIN chimeras), a flaviviral vector, a herpes virus vector (e.g. vectors derived from cytomegaloviruses, like rhesus cytomegalovirus (RhCMV), an arena virus vector (e.g. lymphocytic choriomeningitis virus (LCMV) vectors), a measles virus vector, a BCG vector, a vaccinia vector, a papillomaviral vector, and a poxvirus vector.
- AAV adeno-associated virus
- AAV adeno-associated virus
- VEE Venezuelan equine
- the vector comprises an adenoviral vector.
- the adenoviral vector can be or derived from a human adenovirus vector, a simian adenovirus, etc., or comprises a species B adenovirus vector (e.g., Ad3, 1 Ip, and 35), a species C adenovirus vector (e.g., Adi, Ad 2, Ad5 and Ad6), a species E adenovirus vector (e.g., Ad4), a species F adenovirus vector (e.g., Ad41) or a chimeric Ad5 vector comprising the Adil or Ad35 fibers (Ad5/11 and Ad5/35).
- a species B adenovirus vector e.g., Ad3, 1 Ip, and 35
- a species C adenovirus vector e.g., Adi, Ad 2, Ad5 and Ad6
- a species E adenovirus vector e.g., Ad4
- the adenoviral vector is a human serotype 5 (AdHu5).
- the vector may be an animal derived adenoviral vector for example canine, simian in particular rhesus monkey and chimpanzee.
- the adenoviral vector may be a rare serotype vector derived from a non-human primate. Vectors derived from chimpanzee may be suitable for the vector for the present disclosure, examples include but are not limited to ChAd63, ChAd3, ChAdY25.
- the vector is an adenoviral vector, e.g., an adenoviral vector comprising a polynucleotide sequence encoding a single epitope, e.g., a single T cell epitope, e.g., a single cancer-specific CD8+ epitope, optionally wherein the vector is capable of inducing an inflating memory CD8+ T cell response.
- adenoviral vector e.g., an adenoviral vector comprising a polynucleotide sequence encoding a single epitope, e.g., a single T cell epitope, e.g., a single cancer-specific CD8+ epitope, optionally wherein the vector is capable of inducing an inflating memory CD8+ T cell response.
- the adenoviral vector comprises a polynucleotide sequence encoding a single epitope, e.g., a single T cell epitope, e.g., a single cancer-specific CD8+ epitope, and the vector does not comprise any additional cancer specific CD8+ T cell epitopes.
- the adenoviral vector comprises a polynucleotide sequence encoding multiple epitopes, e.g., multiple T cell epitopes, e.g., multiple cancer-specific CD8+ epitopes.
- the vector is or comprises an AAV vector.
- the AAV vector may be an AAV1, AAV2, AAVS or any combination thereof.
- the AAV vector is selected for delivery to a particular cell, tissue, or organ, e.g., AAV serotypes 1, 2, 5 or a hybrid capsid AAV1, AAV2, AAVS or any combination thereof for targeting brain or neuronal cells; AAV4 for targeting cardiac tissue, and AAV8 for delivery to the liver.
- the vector may be modified to reduce the immunogenicity and improve biosafety of the vector.
- the vector may be replication-deficient.
- the vector may lack the El and E3 proteins.
- the vector may be a recombinant (e.g., engineered) adenoviral vector, wherein the backbone of the recombinant adenoviral vector is an adenovirus serotype 5 (Ad5) nucleic acid backbone.
- the recombinant adenoviral vector may comprise a deletion or a functional deletion of an El gene.
- the recombinant adenoviral vector may comprise a deletion or a functional deletion of an E3 gene.
- the recombinant adenoviral vector may comprise a deletion or a functional deletion of the El and E3 genes.
- the recombinant adenoviral vector may comprise a transgene inserted at the locus of the deleted or functionally deleted El gene.
- the recombinant adenoviral vector may comprise a transgene inserted at the locus of the deleted or functionally deleted E3 gene.
- the transgene insertion may comprise a single cancer-specific CD8+ T cell epitope described herein.
- the transgene insertion may comprise a single cancer- specific CD4+ T cell epitope described herein.
- the transgene insertion may comprise more than one cancer-specific CD4+ T cell epitope.
- the transgene insertion may comprise a cancer-specific CD8+ T cell epitope and a cancer-specific CD4+ T cell epitope.
- a nucleic acid sequence encoding the single cancer-specific CD8+ T cell epitope may be inserted in the El region.
- the vector further comprises a promoter.
- the vector is an in vitro transcribed vector.
- the vector may comprise a strong promoter, examples include but are not limited to a CMV promoter, an RSV promoter, an EFla promoter, a simian virus 40 (SV40) early promoter, a mouse mammary tumor virus (MMTV), a human immunodeficiency virus (HIV) long terminal repeat (LTR) promoter, a MoMuLV promoter, an avian leukemia virus promoter, an Epstein-Barr virus immediate early promoter, a Rous sarcoma virus (RSV) promoter, as well as human gene promoters such as, but not limited to, the actin promoter, the myosin promoter, the elongation factor-la promoter, the hemoglobin promoter, and the creatine kinase promoter.
- the vector comprises a CMV promoter.
- the vector may comprise an inducible promoter.
- inducible promoters include, but are not limited to a metallothionine promoter, a glucocorticoid promoter, a progesterone promoter, and a tetracycline-regulated promoter.
- a vector disclosed herein can comprise additional promoter elements, e.g., enhancers and/or silencers.
- the vector may comprise a TATA box.
- the vector comprises a translation initiation sequence, for example a Kozak sequence.
- a Kozak sequence has the consensus sequence (gcc)gccRccAUGG, a suitable Kozak sequence is provided in SEQ ID NO: 37.
- the vector comprises a termination sequence and/or a polyadenylation sequence.
- a suitable polyadenylation sequence is provided in SEQ ID NO: 43.
- the AAV vector may comprise inverted terminal repeat (ITR) sequences.
- a suitable 3’ ITR sequence is provided in SEQ ID NO: 51.
- a suitable 5’ ITR sequence is provided in SEQ ID NO: 50.
- the viral vector comprises the vector back bone, a promoter region and a nucleotide sequence encoding a single epitope, e.g., a single T cell epitope, e.g., a single cancer-specific CD8+ and/or CD4+ epitope, e.g., a single cancer-specific CD8+ epitope.
- a single epitope e.g., a single T cell epitope, e.g., a single cancer-specific CD8+ and/or CD4+ epitope, e.g., a single cancer-specific CD8+ epitope.
- the ITR sequences flank the encoded the epitope, e.g., the T cell epitope, e.g., the cancer-specific CD8+ and/or CD4+ epitope, e.g., the cancer-specific CD8+ epitope.
- the 5’ ITR sequence may comprise SEQ ID NO: 50.
- the 3’ ITR sequence may comprise SEQ ID NO: 51.
- the vector may comprise sequences 5’ to the cancer specific epitope for example SEQ ID NOs: 44 or 47.
- the vector may comprise sequences 3’ to the cancer specific epitope for example SEQ ID NOs: 45 or 48.
- helper plasmids in order to produce the viral vector comprising the cancer specific CD8+ T cell epitope, helper plasmids may be used.
- a helper plasmid or plasmids may be used to provide genes required for viral vector replication or packaging.
- helper plasmid encodes E2A, E4 and VA adenoviral proteins and or encodes the rep and cap genes of AAV.
- the vector may comprise a sequence as set forth in SEQ ID NOs: 46 or 49.
- the vector may be modified to reduce the immunogenicity and improve biosafety of the vector.
- the vector may be replication-deficient.
- the vector may lack the El and E3 proteins.
- the vector may comprise sequences 5’ to the cancer specific epitope for example SEQ ID NOs: 44 or 47.
- the vector may comprise sequences 3’ to the cancer specific epitope for example SEQ ID NOs: 45 or 48.
- a vector may also be derived from retroviruses such as the lentivirus.
- a vector disclosed herein e.g., a lentiviral vector can transduce non-proliferating cells, such as hepatocytes.
- a vector disclosed herein has low immunogenicity.
- lentivirus refers to a genus of the Retroviridae family. Lentiviruses are unique among the retroviruses in being able to infect non-dividing cells; they can deliver a significant amount of genetic information into the DNA of the host cell, so they are one of the most efficient methods of a gene delivery vector. HIV, SIV, and FIV are all examples of lentiviruses.
- lentiviral vector refers to a vector derived from at least a portion of a lentivirus genome, including especially a self-inactivating lentiviral vector as provided in Milone et al., Mol. Ther. 17(8): 1453-1464 (2009).
- Other examples of lentivirus vectors that may be used in the clinic include but are not limited to, e.g., the LENTIVECTOR TM gene delivery technology from Oxford BioMedica, the LENTIMAXTM vector system from Lentigen, and the like. Nonclinical types of lentiviral vectors are also available and would be known to one skilled in the art.
- the recombinant polypeptide described herein may be used in multi ci str onic vectors or vectors expressing several polypeptides in the same transcriptional unit.
- Such vectors may use internal ribosomal entry sites (IRES). Since IRES are not functional in all hosts and do not allow for the stoichiometric expression of multiple protein, self-cleaving peptides may be used instead. For example, several viral peptides are cleaved during translation and allow for the expression of multiple proteins form a single transcriptional unit.
- Such peptides include 2A-peptides, or 2A- like sequences, from members of the Picornaviridae virus family.
- the recombinant nucleic acid described herein encodes the recombinant polypeptide in frame with the agent, with the two sequences separated by a self-cleaving peptide, such as a 2A sequence, or a T2A sequence.
- a vector disclosed herein can also contain a selectable marker gene and/or a reporter gene or both.
- the selectable marker may be carried on a separate piece of DNA and used in a co-transfection procedure. Both selectable markers and reporter genes may be flanked with appropriate regulatory sequences to enable expression in the host cells.
- Useful selectable markers include, for example, antibiotic-resistance genes, such as neo and the like.
- Reporter genes are used for identifying potentially transfected cells and for evaluating the functionality of regulatory sequences.
- a reporter gene is a gene that is not present in or expressed by the recipient organism or tissue and that encodes a polypeptide whose expression is manifested by some easily detectable property, e.g., enzymatic activity. Expression of the reporter gene is assayed at a suitable time after the DNA has been introduced into the recipient cells.
- Suitable reporter genes may include genes encoding luciferase, beta-galactosidase, chloramphenicol acetyl transferase, secreted alkaline phosphatase, or the green fluorescent protein gene (e.g., Ui-Tei et al., 2000 FEBS Leters 479: 79-82). Suitable expression systems are well known and may be prepared using known techniques or obtained commercially. In general, the construct with the minimal 5’ flanking region showing the highest level of expression of reporter gene is identified as the promoter. Such promoter regions may be linked to a reporter gene and used to evaluate agents for the ability to modulate promoter-driven transcription.
- the vector is a non-viral vector, e.g., a plasmid, a cosmid, a viruslike particle, a bacterial vector, an artificial chromosome, a liposome, a lipid nanoparticle, or an exosome.
- the vector is a bacterial vector, e.g., an attenuated Salmonella typhimurium, Salmonella typhi, Shigella, Bacillus, Lactobacillus, Bacille Calmette-Guerin (BCG), E. coli, Vibrio cholerae, Campylobacter, Listeria.
- the vector is an attenuated and/or a non- pathogenic vector.
- an exemplary non-viral vector is a liposome.
- lipid formulations is contemplated for the introduction of the nucleic acids into a host cell (in vitro, ex vivo or in vivo).
- the nucleic acid may be associated with a lipid.
- the nucleic acid associated with a lipid may be encapsulated in the aqueous interior of a liposome, interspersed within the lipid bilayer of a liposome, attached to a liposome via a linking molecule that is associated with both the liposome and the oligonucleotide, entrapped in a liposome, complexed with a liposome, dispersed in a solution containing a lipid, mixed with a lipid, combined with a lipid, contained as a suspension in a lipid, contained or complexed with a micelle, or otherwise associated with a lipid.
- Lipid, lipid/DNA or lipid/vector associated compositions are not limited to any particular structure in solution.
- Lipids are fatty substances which may be naturally occurring or synthetic lipids.
- lipids include the fatty droplets that naturally occur in the cytoplasm as well as the class of compounds which contain long-chain aliphatic hydrocarbons and their derivatives, such as fatty acids, alcohols, amines, amino alcohols, and aldehydes.
- Lipids suitable for use can be obtained from commercial sources.
- dimyristyl phosphatidylcholine (“D1VIPC”) can be obtained from Sigma, St. Louis, Mo.
- dicetyl phosphate (“DCP”) can be obtained from K & K Laboratories (Plainview, N. Y.)
- cholesterol (“Choi”) can be obtained from Calbiochem-Behring
- dimyristyl phosphatidylglycerol (“DMPG”) and other lipids may be obtained from Avanti Polar Lipids, Inc. (Birmingham, Ala.).
- Stock solutions of lipids in chloroform or chloroform/methanol can be stored at about -20 °C.
- Liposome is a generic term encompassing a variety of single and multilamellar lipid vehicles formed by the generation of enclosed lipid bilayers or aggregates. Liposomes can be characterized as having vesicular structures with a phospholipid bilayer membrane and an inner aqueous medium. Multilamellar liposomes have multiple lipid layers separated by aqueous medium. They form spontaneously when phospholipids are suspended in an excess of aqueous solution.
- the lipid components undergo self-rearrangement before the formation of closed structures and entrap water and dissolved solutes between the lipid bilayers (Ghosh et al., 1991 Glycobiology 5: 505-10).
- compositions that have different structures in solution than the normal vesicular structure are also encompassed.
- the lipids may assume a micellar structure or merely exist as nonuniform aggregates of lipid molecules.
- lipofectamine-nucleic acid complexes are also contemplated.
- the polynucleotide of the present disclosure can be cloned into a number of types of vectors.
- the polynucleotide can be cloned into a vector including, but not limited to a plasmid, a phagemid, a phage derivative, a virus, and a cosmid.
- the polynucleotide can be cloned into a vector including, but not limited to an expression vector, a replication vector, a probe generation vector, and a sequencing vector.
- a vector disclosed herein comprises a recombinant polypeptide disclosed herein, e.g., a recombinant polypeptide comprising a single epitope, e.g., a single T cell epitope, e.g., a single cancer-specific CD8+ and/or CD4+ epitope, e.g., a single cancer-specific CD8+ epitope, e.g., a single cancer-specific CD8+ epitope comprising an amino acid sequence as set forth in any of SEQ ID NOs: 1-35.
- a vector disclosed herein comprises a polynucleotide disclosed herein, e.g., a polynucleotide encoding a recombinant polypeptide disclosed herein, e.g., a recombinant polypeptide comprising a single epitope, e.g., a single T cell epitope, e.g., a single cancer-specific CD8+ and/or CD4+ epitope, e.g., a single cancer-specific CD8+ epitope, comprising an amino acid sequence as set forth in any of SEQ ID NOs: 1-35.
- the vector comprises a single epitope, e.g., a single T cell epitope, e.g., a single cancer-specific CD8+ and/or CD4+ epitope, e.g., a single cancer-specific CD8+ epitope, e.g., a single cancer-specific CD8+ epitope comprising an amino acid sequence as set forth in any of SEQ ID NOs: 1-35.
- a single epitope e.g., a single T cell epitope, e.g., a single cancer-specific CD8+ and/or CD4+ epitope, e.g., a single cancer-specific CD8+ epitope, e.g., a single cancer-specific CD8+ epitope comprising an amino acid sequence as set forth in any of SEQ ID NOs: 1-35.
- the vector can encode a single cancer-specific CD8+ T cell epitope as set forth in SEQ ID NO: 1. In some embodiments, the vector can encode a single cancerspecific CD8+ T cell epitope as set forth in SEQ ID NO: 2. In some embodiments, the vector can encode a single cancer-specific CD8+ T cell epitope as set forth in SEQ ID NO: 3. In some embodiments, the vector can encode a single cancer-specific CD8+ T cell epitope as set forth in SEQ ID NO: 4. In some embodiments, the vector can encode a single cancer-specific CD8+ T cell epitope as set forth in SEQ ID NO: 5.
- the vector can encode a single cancer-specific CD8+ T cell epitope as set forth in SEQ ID NO: 6. In some embodiments, the vector can encode a single cancer-specific CD8+ T cell epitope as set forth in SEQ ID NO: 7. In some embodiments, the vector can encode a single cancer-specific CD8+ T cell epitope as set forth in SEQ ID NO: 8. In some embodiments, the vector can encode a single cancer-specific CD8+ T cell epitope as set forth in SEQ ID NO: 9. In some embodiments, the vector can encode a single cancer-specific CD8+ T cell epitope as set forth in SEQ ID NO: 10.
- the vector can encode a single cancer-specific CD8+ T cell epitope as set forth in SEQ ID NO: 11. In some embodiments, the vector can encode a single cancer-specific CD8+ T cell epitope as set forth in SEQ ID NO: 12. In some embodiments, the vector can encode a single cancer-specific CD8+ T cell epitope as set forth in SEQ ID NO: 13. In some embodiments, the vector can encode a single cancer-specific CD8+ T cell epitope as set forth in SEQ ID NO: 14. In some embodiments, the vector can encode a single cancer-specific CD8+ T cell epitope as set forth in SEQ ID NO: 15.
- the vector can encode a single cancer-specific CD8+ T cell epitope as set forth in SEQ ID NO: 16. In some embodiments, the vector can encode a single cancer-specific CD8+ T cell epitope as set forth in SEQ ID NO: 17. In some embodiments, the vector can encode a single cancer-specific CD8+ T cell epitope as set forth in SEQ ID NO: 18. In some embodiments, the vector can encode a single cancer-specific CD8+ T cell epitope as set forth in SEQ ID NO: 19. In some embodiments, the vector can encode a single cancer-specific CD8+ T cell epitope as set forth in SEQ ID NO: 20.
- the vector can encode a single cancer-specific CD8+ T cell epitope as set forth in SEQ ID NO: 21. In some embodiments, the vector can encode a single cancer-specific CD8+ T cell epitope as set forth in SEQ ID NO: 22. In some embodiments, the vector can encode a single cancer-specific CD8+ T cell epitope as set forth in SEQ ID NO: 23. In some embodiments, the vector can encode a single cancer-specific CD8+ T cell epitope as set forth in SEQ ID NO: 24. In some embodiments, the vector can encode a single cancer-specific CD8+ T cell epitope as set forth in SEQ ID NO: 25.
- the vector can encode a single cancer-specific CD8+ T cell epitope as set forth in SEQ ID NO: 26. In some embodiments, the vector can encode a single cancer-specific CD8+ T cell epitope as set forth in SEQ ID NO: 27. In some embodiments, the vector can encode a single cancer-specific CD8+ T cell epitope as set forth in SEQ ID NO: 28. In some embodiments, the vector can encode a single cancer-specific CD8+ T cell epitope as set forth in SEQ ID NO: 29. In some embodiments, the vector can encode a single cancer-specific CD8+ T cell epitope as set forth in SEQ ID NO: 30.
- the vector can encode a single cancer-specific CD8+ T cell epitope as set forth in SEQ ID NO: 31. In some embodiments, the vector can encode a single cancer-specific CD8+ T cell epitope as set forth in SEQ ID NO: 32. In some embodiments, the vector can encode a single cancer-specific CD8+ T cell epitope as set forth in SEQ ID NO: 33. In some embodiments, the vector can encode a single cancer-specific CD8+ T cell epitope as set forth in SEQ ID NO: 34. In some embodiments, the vector can encode a single cancer-specific CD8+ T cell epitope as set forth in SEQ ID NO: 35.
- the vector encodes a single epitope, e.g., a single T cell epitope, e.g., a single cancer-specific CD8+ and/or CD4+ epitope, e.g., a single cancer-specific CD8+ epitope comprising approximately 5 to approximately 15 amino acids, approximately 6 to approximately 15 amino acids, approximately 7 to approximately 15 amino acids, or approximately 8 to approximately 15 amino acids.
- a single epitope e.g., a single T cell epitope, e.g., a single cancer-specific CD8+ and/or CD4+ epitope, e.g., a single cancer-specific CD8+ epitope comprising approximately 5 to approximately 15 amino acids, approximately 6 to approximately 15 amino acids, approximately 7 to approximately 15 amino acids, or approximately 8 to approximately 15 amino acids.
- the vector encodes a single epitope, e.g., a single T cell epitope, e.g., a single T cell epitope, e.g., a single cancer-specific CD8+ and/or CD4+ epitope, e.g., a single cancer-specific CD8+ epitope selected from GVYDGREHTV, KLVELEHTL, SPSSASLAL, KPRPDVTNEL, KEFAFLEHSL, and HELGFKVVL.
- a single epitope e.g., a single T cell epitope, e.g., a single T cell epitope, e.g., a single cancer-specific CD8+ and/or CD4+ epitope, e.g., a single cancer-specific CD8+ epitope selected from GVYDGREHTV, KLVELEHTL, SPSSASLAL, KPRPDVTNEL, KEFAFLEHSL, and HELGFKVVL.
- the vector encodes two or more (e.g., 2, 3, 4, 5, 6, or more) cancer-specific CD8+ and/or CD4+ T cell epitopes selected from GVYDGREHTV, KLVELEHTL, SPSSASLAL, KPRPDVTNEL, KEFAFLEHSL, and HELGFKVVL, or any combination thereof.
- the vector encodes a single epitope, e.g., a single T cell epitope, e.g., a single T cell epitope, e.g., a single cancer-specific CD8+ and/or CD4+ epitope, e.g., a single cancer-specific CD8+ epitope selected from GVYDGREHTV, KLVELEHTL, SPSSASLAL, KPRPDVTNEL, KEFAFLEHSL, HELGFKVVL, LKPDHIQR, SLFGARPGR, KTEVHGRLK, NLRPPTQEL, RVSLPKLGYK, LRPPTQEL, and RPASPRPAP.
- a single epitope e.g., a single T cell epitope, e.g., a single T cell epitope, e.g., a single cancer-specific CD8+ and/or CD4+ epitope, e.g., a single cancer-specific CD8+ epitop
- the vector encodes two or more (e.g., 2, 3, 4, 5, 6, or more) cancer-specific CD8+ and/or CD4+ T cell epitopes selected from GVYDGREHTV, KLVELEHTL, SPSSASLAL, KPRPDVTNEL, KEFAFLEHSL, HELGFKVVL, LKPDHIQR, SLFGARPGR, KTEVHGRLK, NLRPPTQEL, RVSLPKLGYK, LRPPTQEL, and RPASPRPAP, or any combination thereof.
- two or more (e.g., 2, 3, 4, 5, 6, or more) cancer-specific CD8+ and/or CD4+ T cell epitopes selected from GVYDGREHTV, KLVELEHTL, SPSSASLAL, KPRPDVTNEL, KEFAFLEHSL, HELGFKVVL, LKPDHIQR, SLFGARPGR, KTEVHGRLK, NLRPPTQEL, RVSLPKLGYK, LRPPTQEL,
- the vector encodes a single epitope, e.g., a single T cell epitope, e.g., a single T cell epitope, e.g., a single cancer-specific CD8+ and/or CD4+ epitope, e.g., a single cancer-specific CD8+ epitope selected from GVYDGREHTV, KLVELEHTL, SPSSASLAL, KPRPDVTNEL, KEFAFLEHSL, HELGFKVVL, LKPDHIQR, SLFGARPGR, KTEVHGRLK, NLRPPTQEL, RVSLPKLGYK, LRPPTQEL, RPASPRPAP, IATKIALQM, SLYQTIRLK, KTPLHTLLK, RLHSFTLRQK, RVFTSSLKTK, RVLAKGLAK, GPRPSPTRSV, GQHLHLETF, SPRSPSPSL, VPQEAVRAPL, IYPFINSH
- the vector encodes two or more (e.g., 2, 3, 4, 5, 6, or more) cancer-specific CD8+ and/or CD4+ T cell epitopes selected from GVYDGREHTV, KLVELEHTL, SPSSASLAL, KPRPDVTNEL, KEFAFLEHSL, HELGFKVVL, LKPDHIQR, SLFGARPGR, KTEVHGRLK, NLRPPTQEL, RVSLPKLGYK, LRPPTQEL, RPASPRPAP, IATKIALQM, SLYQTIRLK, KTPLHTLLK, RLHSFTLRQK, RVFTSSLKTK, RVLAKGLAK, GPRPSPTRSV, GQHLHLETF, SPRSPSPSL, VPQEAVRAPL, IYPFINSH, SPSSASLTL, LNKVKTSL, NLKTHLRL, FRGVFVHRY, TSGPVTEKY, and VVAAHLAGA or any combinations thereof.
- the vector encodes two or more (e.g., 2, 3, 4, 5, 6, or more) cancerspecific CD8+ and/or CD4+ T cell epitopes selected from SEQ ID NOs 1-6 or any combinations thereof. In some embodiments, the vector encodes two or more (e.g., 2, 3, 4, 5, 6, or more) cancer-specific CD8+ and/or CD4+ T cell epitopes selected from SEQ ID NOs 7-12 or any combinations thereof. In some embodiments, the vector encodes two or more (e.g., 2, 3, 4, 5, 6, or more) cancer-specific CD8+ and/or CD4+ T cell epitopes selected from SEQ ID NOs 13-18 or any combinations thereof In some embodiments, the vector comprises: (i) a recombinant polypeptide comprising a cancer-specific CD8+ T cell epitope, or (ii) a polynucleotide encoding a recombinant polypeptide comprising a cancer-specific CD8+ T cell epitope); wherein the
- the vector comprises: (i) a recombinant polypeptide consisting of a cancer-specific CD8+ T cell epitope, or (ii) a polynucleotide encoding a recombinant polypeptide consisting of a cancer-specific CD8+ T cell epitope); wherein the cancer-specific CD8+ T cell epitope is GVYDGREHTV.
- the vector comprises: (i) a recombinant polypeptide comprising a cancer-specific CD8+ T cell epitope, or (ii) a polynucleotide encoding a recombinant polypeptide comprising a cancer-specific CD8+ T cell epitope); wherein the cancer-specific CD8+ T cell epitope is KLVELEHTL.
- the vector comprises: (i) a recombinant polypeptide consisting of a cancer-specific CD8+ T cell epitope, or (ii) a polynucleotide encoding a recombinant polypeptide consisting of a cancer-specific CD8+ T cell epitope); wherein the cancer-specific CD8+ T cell epitope is KLVELEHTL.
- the vector comprises: (i) a recombinant polypeptide comprising a cancer-specific CD8+ T cell epitope, or (ii) a polynucleotide encoding a recombinant polypeptide comprising a cancer-specific CD8+ T cell epitope); wherein the cancer-specific CD8+ T cell epitope is SPSSASLAL.
- the vector comprises: (i) a recombinant polypeptide consisting of a cancer-specific CD8+ T cell epitope, or (ii) a polynucleotide encoding a recombinant polypeptide consisting of a cancer-specific CD8+ T cell epitope); wherein the cancer-specific CD8+ T cell epitope is SPSSASLAL.
- the vector comprises: (i) a recombinant polypeptide comprising a cancer-specific CD8+ T cell epitope, or (ii) a polynucleotide encoding a recombinant polypeptide comprising a cancer-specific CD8+ T cell epitope); wherein the cancer-specific CD8+ T cell epitope is KPRPDVTNEL.
- the vector comprises: (i) a recombinant polypeptide consisting of a cancer-specific CD8+ T cell epitope, or (ii) a polynucleotide encoding a recombinant polypeptide consisting of a cancer-specific CD8+ T cell epitope); wherein the cancer-specific CD8+ T cell epitope is KPRPDVTNEL.
- the vector comprises: (i) a recombinant polypeptide comprising a cancer-specific CD8+ T cell epitope, or (ii) a polynucleotide encoding a recombinant polypeptide comprising a cancer-specific CD8+ T cell epitope); wherein the cancer-specific CD8+ T cell epitope is KEFAFLEHSL.
- the vector comprises: (i) a recombinant polypeptide consisting of a cancer-specific CD8+ T cell epitope, or (ii) a polynucleotide encoding a recombinant polypeptide consisting of a cancer-specific CD8+ T cell epitope); wherein the cancer-specific CD8+ T cell epitope is KEFAFLEHSL.
- the vector comprises: (i) a recombinant polypeptide comprising a cancer-specific CD8+ T cell epitope, or (ii) a polynucleotide encoding a recombinant polypeptide comprising a cancer-specific CD8+ T cell epitope); wherein the cancer-specific CD8+ T cell epitope is HELGFKVVL.
- the vector comprises: (i) a recombinant polypeptide consisting of a cancer-specific CD8+ T cell epitope, or (ii) a polynucleotide encoding a recombinant polypeptide consisting of a cancer-specific CD8+ T cell epitope); wherein the cancer-specific CD8+ T cell epitope is HELGFKVVL.
- the vector comprises: (i) a recombinant polypeptide comprising at least two cancer-specific CD8+ T cell epitopes, or (ii) a polynucleotide encoding a recombinant polypeptide comprising at least two cancer-specific CD8+ T cell epitopes, wherein the at least two cancer-specific CD8+ T cell epitopes are GVYDGREHTV and KLVELEHTL.
- the vector comprises: (i) a recombinant polypeptide consisting of at least two cancer-specific CD8+ T cell epitopes, or (ii) a polynucleotide encoding a recombinant polypeptide consisting of at least two cancer-specific CD8+ T cell epitopes wherein the at least two cancer-specific CD8+ T cell epitopes are GVYDGREHTV and KLVELEHTL.
- the vector comprises: (i) a recombinant polypeptide comprising at least two cancer-specific CD8+ T cell epitopes, or (ii) a polynucleotide encoding a recombinant polypeptide comprising at least two cancer-specific CD8+ T cell epitopes, wherein the at least two cancer-specific CD8+ T cell epitopes are GVYDGREHTV and SPSSASLAL.
- the vector comprises: (i) a recombinant polypeptide consisting of at least two cancer-specific CD8+ T cell epitopes, or (ii) a polynucleotide encoding a recombinant polypeptide consisting of at least two cancer-specific CD8+ T cell epitopes wherein the at least two cancer-specific CD8+ T cell epitopes are GVYDGREHTV and SPSSASLAL.
- the vector comprises: (i) a recombinant polypeptide comprising at least two cancer-specific CD8+ T cell epitopes, or (ii) a polynucleotide encoding a recombinant polypeptide comprising at least two cancer-specific CD8+ T cell epitopes, wherein the at least two cancer-specific CD8+ T cell epitopes are GVYDGREHTV and KPRPDVTNEL.
- the vector comprises: (i) a recombinant polypeptide consisting of at least two cancer-specific CD8+ T cell epitopes, or (ii) a polynucleotide encoding a recombinant polypeptide consisting of at least two cancer- specific CD8+ T cell epitopes wherein the at least two cancer-specific CD8+ T cell epitopes are GVYDGREHTV and KPRPDVTNEL.
- the vector comprises: (i) a recombinant polypeptide comprising at least two cancer-specific CD8+ T cell epitopes, or (ii) a polynucleotide encoding a recombinant polypeptide comprising at least two cancer-specific CD8+ T cell epitopes, wherein the at least two cancer-specific CD8+ T cell epitopes are GVYDGREHTV and KEFAFLEHSL.
- the vector comprises: (i) a recombinant polypeptide consisting of at least two cancer-specific CD8+ T cell epitopes, or (ii) a polynucleotide encoding a recombinant polypeptide consisting of at least two cancer-specific CD8+ T cell epitopes wherein the at least two cancer-specific CD8+ T cell epitopes are GVYDGREHTV and KEFAFLEHSL.
- the vector comprises: (i) a recombinant polypeptide comprising at least two cancer-specific CD8+ T cell epitopes, or (ii) a polynucleotide encoding a recombinant polypeptide comprising at least two cancer-specific CD8+ T cell epitopes, wherein the at least two cancer-specific CD8+ T cell epitopes are GVYDGREHTV and HELGFKVVL.
- the vector comprises: (i) a recombinant polypeptide consisting of at least two cancer-specific CD8+ T cell epitopes, or (ii) a polynucleotide encoding a recombinant polypeptide consisting of at least two cancer-specific CD8+ T cell epitopes wherein the at least two cancer-specific CD8+ T cell epitopes are GVYDGREHTV and HELGFKVVL.
- the vector comprises: (i) a recombinant polypeptide comprising at least two cancer-specific CD8+ T cell epitopes, or (ii) a polynucleotide encoding a recombinant polypeptide comprising at least two cancer-specific CD8+ T cell epitopes, wherein the at least two cancer-specific CD8+ T cell epitopes are KLVELEHTL and SPSSASLAL.
- the vector comprises: (i) a recombinant polypeptide consisting of at least two cancer-specific CD8+ T cell epitopes, or (ii) a polynucleotide encoding a recombinant polypeptide consisting of at least two cancer-specific CD8+ T cell epitopes wherein the at least two cancer-specific CD8+ T cell epitopes are KLVELEHTL and SPSSASLAL.
- the vector comprises: (i) a recombinant polypeptide comprising at least two cancer-specific CD8+ T cell epitopes, or (ii) a polynucleotide encoding a recombinant polypeptide comprising at least two cancer-specific CD8+ T cell epitopes, wherein the at least two cancer-specific CD8+ T cell epitopes are KLVELEHTL and KPRPDVTNEL.
- the vector comprises: (i) a recombinant polypeptide consisting of at least two cancer-specific CD8+ T cell epitopes, or (ii) a polynucleotide encoding a recombinant polypeptide consisting of at least two cancer-specific CD8+ T cell epitopes wherein the at least two cancer-specific CD8+ T cell epitopes are KLVELEHTL and KPRPDVTNEL.
- the vector comprises: (i) a recombinant polypeptide comprising at least two cancer-specific CD8+ T cell epitopes, or (ii) a polynucleotide encoding a recombinant polypeptide comprising at least two cancer-specific CD8+ T cell epitopes, wherein the at least two cancer-specific CD8+ T cell epitopes are KLVELEHTL and KEFAFLEHSL.
- the vector comprises: (i) a recombinant polypeptide consisting of at least two cancer-specific CD8+ T cell epitopes, or (ii) a polynucleotide encoding a recombinant polypeptide consisting of at least two cancer-specific CD8+ T cell epitopes wherein the at least two cancer-specific CD8+ T cell epitopes are KLVELEHTL and KEFAFLEHSL.
- the vector comprises: (i) a recombinant polypeptide comprising at least two cancer-specific CD8+ T cell epitopes, or (ii) a polynucleotide encoding a recombinant polypeptide comprising at least two cancer-specific CD8+ T cell epitopes, wherein the at least two cancer-specific CD8+ T cell epitopes are KLVELEHTL and HELGFKVVL.
- the vector comprises: (i) a recombinant polypeptide consisting of at least two cancer-specific CD8+ T cell epitopes, or (ii) a polynucleotide encoding a recombinant polypeptide consisting of at least two cancer-specific CD8+ T cell epitopes wherein the at least two cancer-specific CD8+ T cell epitopes are KLVELEHTL and HELGFKVVL.
- the vector comprises: (i) a recombinant polypeptide comprising at least two cancer-specific CD8+ T cell epitopes, or (ii) a polynucleotide encoding a recombinant polypeptide comprising at least two cancer-specific CD8+ T cell epitopes, wherein the at least two cancer-specific CD8+ T cell epitopes are SPSSASLAL and KPRPDVTNEL.
- the vector comprises: (i) a recombinant polypeptide consisting of at least two cancer-specific CD8+ T cell epitopes, or (ii) a polynucleotide encoding a recombinant polypeptide consisting of at least two cancer-specific CD8+ T cell epitopes wherein the at least two cancer-specific CD8+ T cell epitopes are SPSSASLAL and KPRPDVTNEL.
- the vector comprises: (i) a recombinant polypeptide comprising at least two cancer-specific CD8+ T cell epitopes, or (ii) a polynucleotide encoding a recombinant polypeptide comprising at least two cancer-specific CD8+ T cell epitopes, wherein the at least two cancer-specific CD8+ T cell epitopes are SPSSASLAL and KEFAFLEHSL.
- the vector comprises: (i) a recombinant polypeptide consisting of at least two cancer-specific CD8+ T cell epitopes, or (ii) a polynucleotide encoding a recombinant polypeptide consisting of at least two cancer-specific CD8+ T cell epitopes wherein the at least two cancer-specific CD8+ T cell epitopes are SPSSASLAL and KEFAFLEHSL.
- the vector comprises: (i) a recombinant polypeptide comprising at least two cancer-specific CD8+ T cell epitopes, or (ii) a polynucleotide encoding a recombinant polypeptide comprising at least two cancer-specific CD8+ T cell epitopes, wherein the at least two cancer-specific CD8+ T cell epitopes are SPSSASLAL and HELGFKVVL.
- the vector comprises: (i) a recombinant polypeptide consisting of at least two cancer-specific CD8+ T cell epitopes, or (ii) a polynucleotide encoding a recombinant polypeptide consisting of at least two cancer-specific CD8+ T cell epitopes wherein the at least two cancer-specific CD8+ T cell epitopes are SPSSASLAL and HELGFKVVL.
- the vector comprises: (i) a recombinant polypeptide comprising at least two cancer-specific CD8+ T cell epitopes, or (ii) a polynucleotide encoding a recombinant polypeptide comprising at least two cancer-specific CD8+ T cell epitopes, wherein the at least two cancer-specific CD8+ T cell epitopes are KPRPDVTNEL and KEFAFLEHSL.
- the vector comprises: (i) a recombinant polypeptide consisting of at least two cancer-specific CD8+ T cell epitopes, or (ii) a polynucleotide encoding a recombinant polypeptide consisting of at least two cancer-specific CD8+ T cell epitopes wherein the at least two cancer-specific CD8+ T cell epitopes are KPRPDVTNEL and KEFAFLEHSL.
- the vector comprises: (i) a recombinant polypeptide comprising at least two cancer-specific CD8+ T cell epitopes, or (ii) a polynucleotide encoding a recombinant polypeptide comprising at least two cancer-specific CD8+ T cell epitopes, wherein the at least two cancer-specific CD8+ T cell epitopes are KPRPDVTNEL and HELGFKVVL.
- the vector comprises: (i) a recombinant polypeptide consisting of at least two cancer-specific CD8+ T cell epitopes, or (ii) a polynucleotide encoding a recombinant polypeptide consisting of at least two cancer-specific CD8+ T cell epitopes wherein the at least two cancer-specific CD8+ T cell epitopes are KPRPDVTNEL and HELGFKVVL.
- the vector comprises: (i) a recombinant polypeptide comprising at least two cancer-specific CD8+ T cell epitopes, or (ii) a polynucleotide encoding a recombinant polypeptide comprising at least two cancer-specific CD8+ T cell epitopes, wherein the at least two cancer-specific CD8+ T cell epitopes are KEFAFLEHSL and HELGFKVVL.
- the vector comprises: (i) a recombinant polypeptide consisting of at least two cancer-specific CD8+ T cell epitopes, or (ii) a polynucleotide encoding a recombinant polypeptide consisting of at least two cancer-specific CD8+ T cell epitopes wherein the at least two cancer-specific CD8+ T cell epitopes are KEFAFLEHSL and HELGFKVVL.
- the vector comprises: (i) a recombinant polypeptide comprising at least three cancer-specific CD8+ T cell epitopes, or (ii) a polynucleotide encoding a recombinant polypeptide comprising at least three cancer-specific CD8+ T cell epitopes, wherein the at least three cancer-specific CD8+ T cell epitopes are GVYDGREHTV and KLVELEHTL and SPSSASLAL.
- the vector comprises: (i) a recombinant polypeptide consisting of at least three cancer-specific CD8+ T cell epitopes, or (ii) a polynucleotide encoding a recombinant polypeptide consisting of at least three cancer-specific CD8+ T cell epitopes wherein the at least two cancer-specific CD8+ T cell epitopes are GVYDGREHTV and KLVELEHTL and SPSSASLAL.
- the vector comprises: (i) a recombinant polypeptide comprising at least three cancer-specific CD8+ T cell epitopes, or (ii) a polynucleotide encoding a recombinant polypeptide comprising at least three cancer-specific CD8+ T cell epitopes, wherein the at least three cancer-specific CD8+ T cell epitopes are GVYDGREHTV and KLVELEHTL and KEFAFLEHSL.
- the vector comprises: (i) a recombinant polypeptide consisting of at least three cancer-specific CD8+ T cell epitopes, or (ii) a polynucleotide encoding a recombinant polypeptide consisting of at least three cancer-specific CD8+ T cell epitopes wherein the at least two cancer-specific CD8+ T cell epitopes are GVYDGREHTV and KLVELEHTL and KEFAFLEHSL.
- the vector comprises: (i) a recombinant polypeptide comprising at least three cancer-specific CD8+ T cell epitopes, or (ii) a polynucleotide encoding a recombinant polypeptide comprising at least three cancer-specific CD8+ T cell epitopes, wherein the at least three cancer-specific CD8+ T cell epitopes are GVYDGREHTV and KLVELEHTL and KEFAFLEHSL.
- the vector comprises: (i) a recombinant polypeptide consisting of at least three cancer-specific CD8+ T cell epitopes, or (ii) a polynucleotide encoding a recombinant polypeptide consisting of at least three cancer-specific CD8+ T cell epitopes wherein the at least two cancer-specific CD8+ T cell epitopes are GVYDGREHTV and KLVELEHTL and KEFAFLEHSL.
- the vector comprises: (i) a recombinant polypeptide comprising at least three cancer-specific CD8+ T cell epitopes, or (ii) a polynucleotide encoding a recombinant polypeptide comprising at least three cancer-specific CD8+ T cell epitopes, wherein the at least three cancer-specific CD8+ T cell epitopes are GVYDGREHTV and KLVELEHTL and HELGFKVVL.
- the vector comprises: (i) a recombinant polypeptide consisting of at least three cancer-specific CD8+ T cell epitopes, or (ii) a polynucleotide encoding a recombinant polypeptide consisting of at least three cancer-specific CD8+ T cell epitopes wherein the at least two cancer-specific CD8+ T cell epitopes are GVYDGREHTV and KLVELEHTL and HELGFKVVL.
- the vector comprises: (i) a recombinant polypeptide comprising at least three cancer-specific CD8+ T cell epitopes, or (ii) a polynucleotide encoding a recombinant polypeptide comprising at least three cancer-specific CD8+ T cell epitopes, wherein the at least three cancer-specific CD8+ T cell epitopes are GVYDGREHTV and SPSSASLAL and KPRPDVTNEL.
- the vector comprises: (i) a recombinant polypeptide consisting of at least three cancer-specific CD8+ T cell epitopes, or (ii) a polynucleotide encoding a recombinant polypeptide consisting of at least three cancer-specific CD8+ T cell epitopes wherein the at least two cancer-specific CD8+ T cell epitopes are GVYDGREHTV and SPSSASLAL and KPRPDVTNEL.
- the vector comprises: (i) a recombinant polypeptide comprising at least three cancer-specific CD8+ T cell epitopes, or (ii) a polynucleotide encoding a recombinant polypeptide comprising at least three cancer-specific CD8+ T cell epitopes, wherein the at least three cancer-specific CD8+ T cell epitopes are GVYDGREHTV and SPSSASLAL and KEFAFLEHSL.
- the vector comprises: (i) a recombinant polypeptide consisting of at least three cancer-specific CD8+ T cell epitopes, or (ii) a polynucleotide encoding a recombinant polypeptide consisting of at least three cancer-specific CD8+ T cell epitopes wherein the at least two cancer-specific CD8+ T cell epitopes are GVYDGREHTV and SPSSASLAL and KEFAFLEHSL.
- the vector comprises: (i) a recombinant polypeptide comprising at least three cancer-specific CD8+ T cell epitopes, or (ii) a polynucleotide encoding a recombinant polypeptide comprising at least three cancer-specific CD8+ T cell epitopes, wherein the at least three cancer-specific CD8+ T cell epitopes are GVYDGREHTV and SPSSASLAL and HELGFKVVL.
- the vector comprises: (i) a recombinant polypeptide consisting of at least three cancer-specific CD8+ T cell epitopes, or (ii) a polynucleotide encoding a recombinant polypeptide consisting of at least three cancer-specific CD8+ T cell epitopes wherein the at least two cancer-specific CD8+ T cell epitopes are GVYDGREHTV and SPSSASLAL and HELGFKVVL.
- the vector comprises: (i) a recombinant polypeptide comprising at least three cancer-specific CD8+ T cell epitopes, or (ii) a polynucleotide encoding a recombinant polypeptide comprising at least three cancer-specific CD8+ T cell epitopes, wherein the at least three cancer-specific CD8+ T cell epitopes are GVYDGREHTV and KPRPDVTNEL and KEFAFLEHSL.
- the vector comprises: (i) a recombinant polypeptide consisting of at least three cancer-specific CD8+ T cell epitopes, or (ii) a polynucleotide encoding a recombinant polypeptide consisting of at least three cancer-specific CD8+ T cell epitopes wherein the at least two cancer-specific CD8+ T cell epitopes are GVYDGREHTV and KPRPDVTNEL and KEFAFLEHSL.
- the vector comprises: (i) a recombinant polypeptide comprising at least three cancer-specific CD8+ T cell epitopes, or (ii) a polynucleotide encoding a recombinant polypeptide comprising at least three cancer-specific CD8+ T cell epitopes, wherein the at least three cancer-specific CD8+ T cell epitopes are GVYDGREHTV and KPRPDVTNEL and HELGFKVVL.
- the vector comprises: (i) a recombinant polypeptide consisting of at least three cancer-specific CD8+ T cell epitopes, or (ii) a polynucleotide encoding a recombinant polypeptide consisting of at least three cancer-specific CD8+ T cell epitopes wherein the at least two cancer-specific CD8+ T cell epitopes are GVYDGREHTV and KPRPDVTNEL and HELGFKVVL.
- the vector comprises: (i) a recombinant polypeptide comprising at least three cancer-specific CD8+ T cell epitopes, or (ii) a polynucleotide encoding a recombinant polypeptide comprising at least three cancer-specific CD8+ T cell epitopes, wherein the at least three cancer-specific CD8+ T cell epitopes are GVYDGREHTV and KPRPDVTNEL and HELGFKVVL.
- the vector comprises: (i) a recombinant polypeptide consisting of at least three cancer-specific CD8+ T cell epitopes, or (ii) a polynucleotide encoding a recombinant polypeptide consisting of at least three cancer-specific CD8+ T cell epitopes wherein the at least two cancer-specific CD8+ T cell epitopes are GVYDGREHTV and KPRPDVTNEL and HELGFKVVL.
- the vector comprises: (i) a recombinant polypeptide comprising at least three cancer-specific CD8+ T cell epitopes, or (ii) a polynucleotide encoding a recombinant polypeptide comprising at least three cancer-specific CD8+ T cell epitopes, wherein the at least three cancer-specific CD8+ T cell epitopes are KLVELEHTL and SPSSASLAL and KPRPDVTNEL.
- the vector comprises: (i) a recombinant polypeptide consisting of at least three cancer-specific CD8+ T cell epitopes, or (ii) a polynucleotide encoding a recombinant polypeptide consisting of at least three cancer-specific CD8+ T cell epitopes wherein the at least two cancer-specific CD8+ T cell epitopes are KLVELEHTL and SPSSASLAL and KPRPDVTNEL.
- the vector comprises: (i) a recombinant polypeptide comprising at least three cancer-specific CD8+ T cell epitopes, or (ii) a polynucleotide encoding a recombinant polypeptide comprising at least three cancer-specific CD8+ T cell epitopes, wherein the at least three cancer-specific CD8+ T cell epitopes are KLVELEHTL and SPSSASLAL and KEFAFLEHSL.
- the vector comprises: (i) a recombinant polypeptide consisting of at least three cancer-specific CD8+ T cell epitopes, or (ii) a polynucleotide encoding a recombinant polypeptide consisting of at least three cancer-specific CD8+ T cell epitopes wherein the at least two cancer-specific CD8+ T cell epitopes are KLVELEHTL and SPSSASLAL and KEFAFLEHSL.
- the vector comprises: (i) a recombinant polypeptide comprising at least three cancer-specific CD8+ T cell epitopes, or (ii) a polynucleotide encoding a recombinant polypeptide comprising at least three cancer-specific CD8+ T cell epitopes, wherein the at least three cancer-specific CD8+ T cell epitopes are KLVELEHTL and SPSSASLAL and HELGFKVVL.
- the vector comprises: (i) a recombinant polypeptide consisting of at least three cancer-specific CD8+ T cell epitopes, or (ii) a polynucleotide encoding a recombinant polypeptide consisting of at least three cancer-specific CD8+ T cell epitopes wherein the at least two cancer-specific CD8+ T cell epitopes are KLVELEHTL and SPSSASLAL and HELGFKVVL.
- the vector comprises: (i) a recombinant polypeptide comprising at least three cancer-specific CD8+ T cell epitopes, or (ii) a polynucleotide encoding a recombinant polypeptide comprising at least three cancer-specific CD8+ T cell epitopes, wherein the at least three cancer-specific CD8+ T cell epitopes are KLVELEHTL and KPRPDVTNEL and KEFAFLEHSL.
- the vector comprises: (i) a recombinant polypeptide consisting of at least three cancer-specific CD8+ T cell epitopes, or (ii) a polynucleotide encoding a recombinant polypeptide consisting of at least three cancer-specific CD8+ T cell epitopes wherein the at least two cancer-specific CD8+ T cell epitopes are KLVELEHTL and KPRPDVTNEL and KEFAFLEHSL.
- the vector comprises: (i) a recombinant polypeptide comprising at least three cancer-specific CD8+ T cell epitopes, or (ii) a polynucleotide encoding a recombinant polypeptide comprising at least three cancer-specific CD8+ T cell epitopes, wherein the at least three cancer-specific CD8+ T cell epitopes are KLVELEHTL and KPRPDVTNEL and HELGFKVVL.
- the vector comprises: (i) a recombinant polypeptide consisting of at least three cancer-specific CD8+ T cell epitopes, or (ii) a polynucleotide encoding a recombinant polypeptide consisting of at least three cancer-specific CD8+ T cell epitopes wherein the at least two cancer-specific CD8+ T cell epitopes are KLVELEHTL and KPRPDVTNEL and HELGFKVVL.
- the vector comprises: (i) a recombinant polypeptide comprising at least three cancer-specific CD8+ T cell epitopes, or (ii) a polynucleotide encoding a recombinant polypeptide comprising at least three cancer-specific CD8+ T cell epitopes, wherein the at least three cancer-specific CD8+ T cell epitopes are KLVELEHTL and KEFAFLEHSL and HELGFKVVL.
- the vector comprises: (i) a recombinant polypeptide consisting of at least three cancer-specific CD8+ T cell epitopes, or (ii) a polynucleotide encoding a recombinant polypeptide consisting of at least three cancer-specific CD8+ T cell epitopes wherein the at least two cancer-specific CD8+ T cell epitopes are KLVELEHTL and KPRPDVTNEL and HELGFKVVL.
- the vector comprises: (i) a recombinant polypeptide comprising at least three cancer-specific CD8+ T cell epitopes, or (ii) a polynucleotide encoding a recombinant polypeptide comprising at least three cancer-specific CD8+ T cell epitopes, wherein the at least three cancer-specific CD8+ T cell epitopes are SPSSASLAL and KPRPDVTNEL and KEFAFLEHSL.
- the vector comprises: (i) a recombinant polypeptide consisting of at least three cancer-specific CD8+ T cell epitopes, or (ii) a polynucleotide encoding a recombinant polypeptide consisting of at least three cancer-specific CD8+ T cell epitopes wherein the at least two cancer-specific CD8+ T cell epitopes are SPSSASLAL and KPRPDVTNEL and KEFAFLEHSL.
- the vector comprises: (i) a recombinant polypeptide comprising at least three cancer-specific CD8+ T cell epitopes, or (ii) a polynucleotide encoding a recombinant polypeptide comprising at least three cancer-specific CD8+ T cell epitopes, wherein the at least three cancer-specific CD8+ T cell epitopes are SPSSASLAL and KPRPDVTNEL and HELGFKVVL.
- the vector comprises: (i) a recombinant polypeptide consisting of at least three cancer-specific CD8+ T cell epitopes, or (ii) a polynucleotide encoding a recombinant polypeptide consisting of at least three cancer-specific CD8+ T cell epitopes wherein the at least two cancer-specific CD8+ T cell epitopes are SPSSASLAL and KPRPDVTNEL and HELGFKVVL.
- the vector comprises: (i) a recombinant polypeptide comprising at least three cancer-specific CD8+ T cell epitopes, or (ii) a polynucleotide encoding a recombinant polypeptide comprising at least three cancer-specific CD8+ T cell epitopes, wherein the at least three cancer-specific CD8+ T cell epitopes are SPSSASLAL and KEFAFLEHSL and HELGFKVVL.
- the vector comprises: (i) a recombinant polypeptide consisting of at least three cancer-specific CD8+ T cell epitopes, or (ii) a polynucleotide encoding a recombinant polypeptide consisting of at least three cancer-specific CD8+ T cell epitopes wherein the at least two cancer-specific CD8+ T cell epitopes are SPSSASLAL and KEFAFLEHSL and HELGFKVVL.
- the vector comprises: (i) a recombinant polypeptide comprising at least three cancer-specific CD8+ T cell epitopes, or (ii) a polynucleotide encoding a recombinant polypeptide comprising at least three cancer-specific CD8+ T cell epitopes, wherein the at least three cancer-specific CD8+ T cell epitopes are KPRPDVTNEL and KEFAFLEHSL and HELGFKVVL.
- the vector comprises: (i) a recombinant polypeptide consisting of at least three cancer-specific CD8+ T cell epitopes, or (ii) a polynucleotide encoding a recombinant polypeptide consisting of at least three cancer-specific CD8+ T cell epitopes wherein the at least two cancer-specific CD8+ T cell epitopes are KPRPDVTNEL and KEFAFLEHSL and HELGFKVVL.
- the vector comprises: (i) a recombinant polypeptide comprising at least four cancer-specific CD8+ T cell epitopes, or (ii) a polynucleotide encoding a recombinant polypeptide comprising at least four cancer-specific CD8+ T cell epitopes, wherein the at least four cancer-specific CD8+ T cell epitopes are GVYDGREHTV and KLVELEHTL and SPSSASLAL and KPRPDVTNEL.
- the vector comprises: (i) a recombinant polypeptide consisting of at least four cancer-specific CD8+ T cell epitopes, or (ii) a polynucleotide encoding a recombinant polypeptide consisting of at least four cancer-specific CD8+ T cell epitopes, wherein the at least four cancer-specific CD8+ T cell epitopes are GVYDGREHTV and KLVELEHTL and SPSSASLAL and KPRPDVTNEL.
- the vector comprises: (i) a recombinant polypeptide comprising at least four cancer-specific CD8+ T cell epitopes, or (ii) a polynucleotide encoding a recombinant polypeptide comprising at least four cancer-specific CD8+ T cell epitopes, wherein the at least four cancer-specific CD8+ T cell epitopes are GVYDGREHTV and KLVELEHTL and SPSSASLAL and KEFAFLEHSL.
- the vector comprises: (i) a recombinant polypeptide consisting of at least four cancer-specific CD8+ T cell epitopes, or (ii) a polynucleotide encoding a recombinant polypeptide consisting of at least four cancer-specific CD8+ T cell epitopes, wherein the at least four cancer-specific CD8+ T cell epitopes are GVYDGREHTV and KLVELEHTL and SPSSASLAL and KEFAFLEHSL.
- the vector comprises: (i) a recombinant polypeptide comprising at least four cancer-specific CD8+ T cell epitopes, or (ii) a polynucleotide encoding a recombinant polypeptide comprising at least four cancer-specific CD8+ T cell epitopes, wherein the at least four cancer-specific CD8+ T cell epitopes are GVYDGREHTV and KLVELEHTL and SPSSASLAL and HELGFKVVL.
- the vector comprises: (i) a recombinant polypeptide consisting of at least four cancer-specific CD8+ T cell epitopes, or (ii) a polynucleotide encoding a recombinant polypeptide consisting of at least four cancer-specific CD8+ T cell epitopes, wherein the at least four cancer-specific CD8+ T cell epitopes are GVYDGREHTV and KLVELEHTL and SPSSASLAL and HELGFKVVL.
- the vector comprises: (i) a recombinant polypeptide comprising at least four cancer-specific CD8+ T cell epitopes, or (ii) a polynucleotide encoding a recombinant polypeptide comprising at least four cancer-specific CD8+ T cell epitopes, wherein the at least four cancer-specific CD8+ T cell epitopes are GVYDGREHTV and SPSSASLAL and KPRPDVTNEL and KEFAFLEHSL.
- the vector comprises: (i) a recombinant polypeptide consisting of at least four cancer-specific CD8+ T cell epitopes, or (ii) a polynucleotide encoding a recombinant polypeptide consisting of at least four cancer-specific CD8+ T cell epitopes, wherein the at least four cancer-specific CD8+ T cell epitopes are GVYDGREHTV and SPSSASLAL and KPRPDVTNEL and KEFAFLEHSL.
- the vector comprises: (i) a recombinant polypeptide comprising at least four cancer-specific CD8+ T cell epitopes, or (ii) a polynucleotide encoding a recombinant polypeptide comprising at least four cancer-specific CD8+ T cell epitopes, wherein the at least four cancer-specific CD8+ T cell epitopes are GVYDGREHTV and SPSSASLAL and KPRPDVTNEL and HELGFKVVL.
- the vector comprises: (i) a recombinant polypeptide consisting of at least four cancer-specific CD8+ T cell epitopes, or (ii) a polynucleotide encoding a recombinant polypeptide consisting of at least four cancer-specific CD8+ T cell epitopes, wherein the at least four cancer-specific CD8+ T cell epitopes are GVYDGREHTV and SPSSASLAL and KPRPDVTNEL and HELGFKVVL.
- the vector comprises: (i) a recombinant polypeptide comprising at least four cancer-specific CD8+ T cell epitopes, or (ii) a polynucleotide encoding a recombinant polypeptide comprising at least four cancer-specific CD8+ T cell epitopes, wherein the at least four cancer-specific CD8+ T cell epitopes are GVYDGREHTV and KPRPDVTNEL and KEFAFLEHSL and HELGFKVVL.
- the vector comprises: (i) a recombinant polypeptide consisting of at least four cancer-specific CD8+ T cell epitopes, or (ii) a polynucleotide encoding a recombinant polypeptide consisting of at least four cancer-specific CD8+ T cell epitopes, wherein the at least four cancer-specific CD8+ T cell epitopes are GVYDGREHTV and KPRPDVTNEL and KEFAFLEHSL and HELGFKVVL.
- the vector comprises: (i) a recombinant polypeptide comprising at least four cancer-specific CD8+ T cell epitopes, or (ii) a polynucleotide encoding a recombinant polypeptide comprising at least four cancer-specific CD8+ T cell epitopes, wherein the at least four cancer-specific CD8+ T cell epitopes are KLVELEHTL and SPSSASLAL and KPRPDVTNEL and KEFAFLEHSL.
- the vector comprises: (i) a recombinant polypeptide consisting of at least four cancer-specific CD8+ T cell epitopes, or (ii) a polynucleotide encoding a recombinant polypeptide consisting of at least four cancer-specific CD8+ T cell epitopes, wherein the at least four cancer-specific CD8+ T cell epitopes are KLVELEHTL and SPSSASLAL and KPRPDVTNEL and KEFAFLEHSL.
- the vector comprises: (i) a recombinant polypeptide comprising at least four cancer-specific CD8+ T cell epitopes, or (ii) a polynucleotide encoding a recombinant polypeptide comprising at least four cancer-specific CD8+ T cell epitopes, wherein the at least four cancer-specific CD8+ T cell epitopes KLVELEHTL and SPSSASLAL and KPRPDVTNEL and HELGFKVVL.
- the vector comprises: (i) a recombinant polypeptide consisting of at least four cancer-specific CD8+ T cell epitopes, or (ii) a polynucleotide encoding a recombinant polypeptide consisting of at least four cancer-specific CD8+ T cell epitopes, wherein the at least four cancer-specific CD8+ T cell epitopes are KLVELEHTL and SPSSASLAL and KPRPDVTNEL and HELGFKVVL.
- the vector comprises: (i) a recombinant polypeptide comprising at least four cancer-specific CD8+ T cell epitopes, or (ii) a polynucleotide encoding a recombinant polypeptide comprising at least four cancer-specific CD8+ T cell epitopes, wherein the at least four cancer-specific CD8+ T cell epitopes KLVELEHTL and KPRPDVTNEL and KEFAFLEHSL and HELGFKVVL.
- the vector comprises: (i) a recombinant polypeptide consisting of at least four cancer-specific CD8+ T cell epitopes, or (ii) a polynucleotide encoding a recombinant polypeptide consisting of at least four cancer-specific CD8+ T cell epitopes, wherein the at least four cancer-specific CD8+ T cell epitopes are KLVELEHTL and KPRPDVTNEL and KEFAFLEHSL and HELGFKVVL.
- the vector comprises: (i) a recombinant polypeptide comprising at least four cancer-specific CD8+ T cell epitopes, or (ii) a polynucleotide encoding a recombinant polypeptide comprising at least four cancer-specific CD8+ T cell epitopes, wherein the at least four cancer-specific CD8+ T cell epitopes SPSSASLAL and KPRPDVTNEL and KEFAFLEHSL and HELGFKVVL.
- the vector comprises: (i) a recombinant polypeptide consisting of at least four cancer-specific CD8+ T cell epitopes, or (ii) a polynucleotide encoding a recombinant polypeptide consisting of at least four cancer-specific CD8+ T cell epitopes, wherein the at least four cancer-specific CD8+ T cell epitopes are SPSSASLAL and KPRPDVTNEL and KEFAFLEHSL and HELGFKVVL.
- the vector comprises: (i) a recombinant polypeptide comprising at least five cancer-specific CD8+ T cell epitopes, or (ii) a polynucleotide encoding a recombinant polypeptide comprising at least five cancer-specific CD8+ T cell epitopes, wherein the at least five cancer-specific CD8+ T cell epitopes are GVYDGREHTV and KLVELEHTL and SPSSASLAL and KPRPDVTNEL and KEFAFLEHSL.
- the vector comprises: (i) a recombinant polypeptide consisting of at least five cancer-specific CD8+ T cell epitopes, or (ii) a polynucleotide encoding a recombinant polypeptide consisting of at least five cancer-specific CD8+ T cell epitopes, wherein the at least five cancer-specific CD8+ T cell epitopes are GVYDGREHTV and KLVELEHTL and SPSSASLAL and KPRPDVTNEL and KEFAFLEHSL.
- the vector comprises: (i) a recombinant polypeptide comprising at least five cancer-specific CD8+ T cell epitopes, or (ii) a polynucleotide encoding a recombinant polypeptide comprising at least five cancer-specific CD8+ T cell epitopes, wherein the at least five cancer-specific CD8+ T cell epitopes are GVYDGREHTV and KLVELEHTL and SPSSASLAL and KPRPDVTNEL and HELGFKVVL.
- the vector comprises: (i) a recombinant polypeptide consisting of at least five cancer-specific CD8+ T cell epitopes, or (ii) a polynucleotide encoding a recombinant polypeptide consisting of at least five cancer-specific CD8+ T cell epitopes, wherein the at least five cancer-specific CD8+ T cell epitopes are GVYDGREHTV and KLVELEHTL and SPSSASLAL and KPRPDVTNEL and HELGFKVVL.
- the vector comprises: (i) a recombinant polypeptide comprising at least five cancer-specific CD8+ T cell epitopes, or (ii) a polynucleotide encoding a recombinant polypeptide comprising at least five cancer-specific CD8+ T cell epitopes, wherein the at least five cancer-specific CD8+ T cell epitopes are GVYDGREHTV and SPSSASLAL and KPRPDVTNEL and KEFAFLEHSL and HELGFKVVL.
- the vector comprises: (i) a recombinant polypeptide consisting of at least five cancer-specific CD8+ T cell epitopes, or (ii) a polynucleotide encoding a recombinant polypeptide consisting of at least five cancer-specific CD8+ T cell epitopes, wherein the at least five cancer-specific CD8+ T cell epitopes are GVYDGREHTV and SPSSASLAL and KPRPDVTNEL and KEFAFLEHSL and HELGFKVVL.
- the vector comprises: (i) a recombinant polypeptide comprising at least five cancer-specific CD8+ T cell epitopes, or (ii) a polynucleotide encoding a recombinant polypeptide comprising at least five cancer-specific CD8+ T cell epitopes, wherein the at least five cancer-specific CD8+ T cell epitopes are KLVELEHTL and SPSSASLAL and KPRPDVTNEL and KEFAFLEHSL and HELGFKVVL.
- the vector comprises: (i) a recombinant polypeptide consisting of at least five cancer-specific CD8+ T cell epitopes, or (ii) a polynucleotide encoding a recombinant polypeptide consisting of at least five cancer-specific CD8+ T cell epitopes, wherein the at least five cancer-specific CD8+ T cell epitopes are KLVELEHTL and SPSSASLAL and KPRPDVTNEL and KEFAFLEHSL and HELGFKVVL.
- the vector comprises: (i) a recombinant polypeptide comprising at least five cancer-specific CD8+ T cell epitopes, or (ii) a polynucleotide encoding a recombinant polypeptide comprising at least five cancer-specific CD8+ T cell epitopes, wherein the at least five cancer-specific CD8+ T cell epitopes are GVYDGREHTV and KLVELEHTL and KPRPDVTNEL and KEFAFLEHSL and HELGFKVVL.
- the vector comprises: (i) a recombinant polypeptide consisting of at least five cancer-specific CD8+ T cell epitopes, or (ii) a polynucleotide encoding a recombinant polypeptide consisting of at least five cancer-specific CD8+ T cell epitopes, wherein the at least five cancer-specific CD8+ T cell epitopes are GVYDGREHTV and KLVELEHTL and KPRPDVTNEL and KEFAFLEHSL and HELGFKVVL.
- the vector comprises: (i) a recombinant polypeptide comprising at least five cancer-specific CD8+ T cell epitopes, or (ii) a polynucleotide encoding a recombinant polypeptide comprising at least five cancer-specific CD8+ T cell epitopes, wherein the at least five cancer-specific CD8+ T cell epitopes are GVYDGREHTV and KLVELEHTL and KPRPDVTNEL and KEFAFLEHSL and HELGFKVVL.
- the vector comprises: (i) a recombinant polypeptide consisting of at least five cancer-specific CD8+ T cell epitopes, or (ii) a polynucleotide encoding a recombinant polypeptide consisting of at least five cancer-specific CD8+ T cell epitopes, wherein the at least five cancer-specific CD8+ T cell epitopes are GVYDGREHTV and KLVELEHTL and KPRPDVTNEL and KEFAFLEHSL and HELGFKVVL.
- the vector comprises: (i) a recombinant polypeptide comprising at least five cancer-specific CD8+ T cell epitopes, or (ii) a polynucleotide encoding a recombinant polypeptide comprising at least five cancer-specific CD8+ T cell epitopes, wherein the at least five cancer-specific CD8+ T cell epitopes are GVYDGREHTV and KLVELEHTL and SPSSASLAL and KEFAFLEHSL and HELGFKVVL.
- the vector comprises: (i) a recombinant polypeptide consisting of at least five cancer-specific CD8+ T cell epitopes, or (ii) a polynucleotide encoding a recombinant polypeptide consisting of at least five cancer-specific CD8+ T cell epitopes, wherein the at least five cancer-specific CD8+ T cell epitopes are GVYDGREHTV and KLVELEHTL and SPSSASLAL and KEFAFLEHSL and HELGFKVVL.
- the vector comprises: (i) a recombinant polypeptide comprising at least six cancer-specific CD8+ T cell epitopes, or (ii) a polynucleotide encoding a recombinant polypeptide comprising at least six cancer-specific CD8+ T cell epitopes, wherein the at least six cancer-specific CD8+ T cell epitopes are GVYDGREHTV and KLVELEHTL and SPSSASLAL and KPRPDVTNEL and KEFAFLEHSL and HELGFKVVL.
- the vector comprises: (i) a recombinant polypeptide comprising at least six cancer-specific CD8+ T cell epitopes, or (ii) a polynucleotide encoding a recombinant polypeptide comprising at least six cancer-specific CD8+ T cell epitopes, wherein the at least six cancer-specific CD8+ T cell epitopes are GVYDGREHTV and KLVELEHTL and SPSSASLAL and KPRPDVTNEL and KEFAFLEHSL and HELGFKVVL.
- the vector comprises a sequence with at least 90% sequence identity to SEQ ID NO: 44 and a sequence with at least 90% sequence identity to SEQ ID NO: 45. In some embodiments, the vector further comprises a sequence with at least 90% sequence identity to SEQ ID NO: 47 and a sequence with at least 90% sequence identity to SEQ ID NO: 48.
- Cancer specific CD8+ T cell epitopes may be determined using techniques know in the art such as proteomics approaches, mass spectrometry approaches, genomic approaches, transcriptome analysis, bioinformatics approaches and in silico methods. It would be possible for the skilled person to select an appropriate epitope to be encoded within the vector of the present disclosure.
- the vector can be readily introduced into a host cell, e.g., mammalian, bacterial, yeast, or insect cell by any method in the art.
- the vector can be transferred into a host cell by physical, chemical, or biological means.
- Physical methods for introducing a polynucleotide into a host cell include calcium phosphate precipitation, lipofection, particle bombardment, microinjection, electroporation, polymer encapsulation, peptide mediated transfection, or biolistic particle delivery systems such as “gene guns” and the like.
- Methods for producing cells comprising vectors and/or exogenous nucleic acids are well-known in the art. See, for example, Sambrook et al., 2012, Molecular Cloning: A Laboratory Manual, volumes 1-4, Cold Spring Harbor Press, NY).
- a non-limiting example for the introduction of a polynucleotide into a host cell is calcium phosphate transfection.
- Biological methods for introducing a polynucleotide of interest into a host cell include the use of DNA and RNA vectors.
- Viral vectors, and especially retroviral vectors have become the most widely used method for inserting genes into mammalian, e.g., human cells.
- Other viral vectors can be derived from lentivirus, poxviruses, herpes simplex virus I, adenoviruses and adeno-associated viruses, and the like (see, e.g., U.S. Pat. Nos. 5,350,674 and 5,585,362.
- Chemical means for introducing a polynucleotide into a host cell include colloidal dispersion systems, such as macromolecule complexes, nanocapsules, nanoparticles, lipid nanoparticle conjugates, microspheres, beads, and lipid-based systems including oil-in-water emulsions, micelles, mixed micelles, and liposomes.
- An exemplary colloidal system for use as a delivery vehicle in vitro and in vivo is a liposome (e.g., an artificial membrane vesicle).
- Other methods of state-of-the-art targeted delivery of nucleic acids are available, such as delivery of polynucleotides with targeted nanoparticles or other suitable sub-micron sized delivery system.
- assays include, for example, “molecular biological” assays well known to those of skill in the art, such as Southern and Northern blotting, RT-PCR and PCR; “biochemical” assays, such as detecting the presence or absence of a particular peptide, e.g., by immunological means (ELISAs and western blots) or by assays described herein to identify agents falling within the scope of the present disclosure.
- moleukin assays well known to those of skill in the art, such as Southern and Northern blotting, RT-PCR and PCR
- biochemical assays, such as detecting the presence or absence of a particular peptide, e.g., by immunological means (ELISAs and western blots) or by assays described herein to identify agents falling within the scope of the present disclosure.
- the present disclosure provides a cell comprising (i) a recombinant polypeptide comprising a single epitope, e.g., a single T cell epitope, e.g., a single cancer-specific CD8+ and/or CD4+ epitope, e.g., a single cancer-specific CD8+ epitope, comprising an amino acid sequence as set forth in any of SEQ ID NOs: 1-35, or (ii) a polynucleotide encoding a recombinant polypeptide comprising a single epitope, e.g., a single T cell epitope, e.g., a single cancer-specific CD8+ and/or CD4+ epitope, e.g., a single cancer-specific CD8+ epitope comprising an amino acid sequence as set forth in any of SEQ ID NOs: 1-35.
- the cell can be an antigen presenting cell (APC). In some embodiments, the cell can be a T cell stimulated with an APC described herein. In some embodiments, the cell comprises a CD8+ T cell. In some embodiments, the cell comprises a CD4+ T cell. In some embodiments, the cell is an inflating memory T cell, e.g., an inflating memory CD8+ T cell.
- APC antigen presenting cell
- the cell can be a T cell stimulated with an APC described herein.
- the cell comprises a CD8+ T cell. In some embodiments, the cell comprises a CD4+ T cell. In some embodiments, the cell is an inflating memory T cell, e.g., an inflating memory CD8+ T cell.
- the present disclosure provides a population of cells wherein a cell in the population comprises (i) a recombinant polypeptide comprising a single epitope, e.g., a single T cell epitope, e.g., a single cancer-specific CD8+ epitope, e.g., a single cancer-specific CD8+ epitope comprising an amino acid sequence as set forth in any of SEQ ID NOs: 1-35, or (ii) a polynucleotide encoding a recombinant polypeptide comprising a single epitope, e.g., a single T cell epitope, e.g., a single cancer-specific CD8+ epitope, e.g., a single cancer-specific CD8+ epitope comprising an amino acid sequence as set forth in any of SEQ ID NOs: 1-35.
- the population of cells comprises a plurality of APCs.
- the plurality of APCs comprise (i) a recombinant polypeptide comprising a single epitope, e.g., a single T cell epitope, e.g., a single cancer-specific CD8+ epitope, e.g., a single cancer-specific CD8+ epitope comprising an amino acid sequence as set forth in any of SEQ ID NOs: 1-35, or (ii) a polynucleotide encoding a recombinant polypeptide comprising a single epitope, e.g., a single T cell epitope, e.g., a single cancer-specific CD8+ epitope, e.g., a single cancer-specific CD8+ epitope comprising an amino acid sequence as set forth in any of SEQ ID NOs: 1-35.
- the population of cells comprises a plurality of T cells stimulated with an APC described herein. In some embodiments, the population of cells comprises a plurality of CD8+ T cells. In some embodiments, the population of cells comprises a plurality of CD4+ T cells. In some embodiments, the population of cells comprises a plurality of inflating memory T cells, e.g., inflating memory CD8+ T cells.
- Inflating memory T cells described herein can be characterized by the presences of specific markers and cell surface markers. Methods to identify and quantify these markers are well known in the art. Examples of suitable methods include but are not limited to affinity -based separation methods, magnetic cell sorting techniques, fluorescence-based cell sorting techniques such as FACS (fluorescence activated cell sorting).
- the inflating memory CD8+ T cells can be characterized by the presence of a number of markers, examples include but are not limited to CX3CR1, KLRG-1, CD44.
- the inflating memory CD8+ T cells can also be characterized by the low expression of a number of markers, example include but are not limited to CD62L, CD27, CD127.
- the term “low expression” may refer to cells wherein there is no expression of the markers, it may also refer to cells wherein there is low expression of the markers relative to other cells in the sample.
- the population of cells comprises a plurality of inflating memory T cells, e.g., a plurality of inflating memory CD8+ T cells, e.g., a plurality of inflating memory CD8+ T cells wherein an inflating memory CD8+ T cell of the population expresses one or more of CX3CR1, KLRG-1, CD44 and/or have low expression of one or more of CD62L, CD27, CD 127.
- the inflating memory CD8+ T cells described herein are characterized by markers selected from the group comprising CX3CR1+, KLRG-1+, CD44+, CD62L-, CCR7-, CD45RA+/- wherein the designation (+) indicates the presence of the marker, and the designation (-) indicates low expression or no expression of the marker; wherein the (-)
- the inflating memory CD8+ T cells may be characterized by one or more markers selected from the group comprising CX3CR1+, KLRG-1+, CD44+, CD62L-, CCR7-, CD45RA+/-, CD27-(low), and/or CD127-(low).
- the inflating memory CD8+ T cells may be characterized by the phenotype CX3CR1+, KLRG-1+, CD44+, CD62L-, CCR7-, CD45RA+/-.
- the inflating memory CD8+ T cells may be characterized by the phenotype CX3CR1+, KLRG-1+, CD44+, CD62L-, CCR7-, CD45RA+/-, CD27-(low), CD 127- (low).
- the CD8+ T cells produced in an inflating memory response may have a number of other characteristics.
- the cells may comprise a transcriptional profile driven by Tbx21 (also referred to as T-bet). These cells show a sustained expression of Tbx21.
- the cells may also show a sustained expression of E2f2 a transcription factor generally involved in cell growth and proliferation.
- the cells may also lack expression or have low expression of the transcription factor Eomes.
- the cell comprising a recombinant polypeptide comprising a single epitope e.g., a single T cell epitope, e.g., a single cancer-specific CD8+ and/or CD4+ epitope, e.g., a single cancer-specific CD8+ epitope
- a single epitope e.g., a single T cell epitope, e.g., a single cancer-specific CD8+ and/or CD4+ epitope, e.g., a single cancer-specific CD8+ epitope
- the cell comprising a recombinant polypeptide comprising a single epitope e.g., a single T cell epitope, e.g., a single cancer-specific CD8+ and/or CD4+ epitope, e.g., a single cancer-specific CD8+ epitope
- a sustained expression of E2f2 comprises a sustained expression of E2f2.
- the cell comprising a single epitope, e.g., a single T cell epitope, e.g., a single cancer-specific CD8+ and/or CD4+ epitope, e.g., a single cancer-specific CD8+ epitope comprises a low expression of the transcription factor Eomes.
- the inflating memory CD8+ T cells may not demonstrate classical contraction after exposure to an antigen. During classical memory evolution after exposure to an antigen, the cells form a contracted central memory pool which makes up ⁇ 1% of total circulating CD8+ T cells. However, inflating memory cells are maintained as large pools of cells which circulate in the blood. As such, the resulting inflating memory CD8+ T cells form approximately 0.01% to approximately 20% of total CD8+ T cells.
- the population of inflating memory CD8+ T cells comprises 0.01%, 0.02%, 0.03%, 0.05%, 0.07%, 0.09%, 0.1%, 0.3%, 0.5%, 0.7%, 0.9%, 1%, 2%, 3%, 4%, 5%, 6%, 7%, 8%, 9%, 10%, 11%, 12%, 13%, 14%, 15%, 16%, 17%, 18%, 19%, or 20% of total CD8+ T cells.
- the population of inflating memory CD8+ T cells comprises approximately 0.1% to approximately 20%, approximately 0.05% to approximately 20%, approximately 0.5% to approximately 20%, approximately 1% to approximately 20%, approximately 2% to approximately 20%, approximately 3% to approximately 20%, approximately 5% to approximately 20%, approximately 8% to approximately 20%, approximately 10% to approximately 20%, approximately 12% to approximately 20%, approximately 15% to approximately 20%, or approximately 18% to approximately 20% of total CD8+ T cells. In some embodiments, the population of inflating memory CD8+ T cells comprises approximately 12% to approximately 20% of total CD8+ T cells.
- the population of inflating memory CD8+ T cells can retain their effector memory phenotype.
- the resulting inflating memory CD8+ T cells can retain their memory effector phenotype for a prolonged period, wherein the effector phenotype is characterized by CD44+ and/or CD62L-.
- the inflating memory CD8+ T cells may retain their memory effector phenotype for up to 60 days post exposure to the vector of the present disclosure.
- the population of inflating memory CD8+ T cells may retain their memory effector phenotype for up to 1 hour, 2 hours, 3 hours, 4 hours, 5 hours, 6 hours, 7 hours, 8 hours, 9 hours, 10 hours, 11 hours, 12 hours, 13 hours, 14 hours, 15 hours, 16 hours, 17 hours, 18 hours, 19 hours, 20 hours, 21 hours, 22 hours, 23 hours, 24 hours or longer post exposure to the vector of the present disclosure.
- the population of inflating memory CD8+ T cells may retain their memory effector phenotype for up to 1 day, 2 days, 3 days, 4 days, 5 days, 6 days, 7 days, 8 days, 9 days, 10 days, 11 days, 12 days, 13 days, 15 days, 17 days, 20 days, 25 days, 30 days, 35 days, 40 days, 50 days, 55 days, 60 days or longer post exposure to the vector of the present disclosure.
- the inflating memory CD8+ T cells may lack markers of exhaustion.
- T cell exhaustion can occur from excessive TCR (T cell receptor) stimulation.
- Markers of T cell exhaustion can include but are not limited to upregulation of markers such as PD-1, Tim-3, or Lag-3.
- the inflating memory CD8+ T cells may lack or demonstrate low expression of markers selected from the group consisting of, but not limited to, PD-1, Tim-3, and/or Lag-3.
- the T cells describe herein can demonstrate a distinct transcriptional profile from both central memory and exhausted memory T cell subsets.
- the T cells describe herein can demonstrate features such as enhanced redox resilience which may be due to intrinsically lower levels of reactive oxygen species and resilience to oxidative stress.
- the transcriptional profile is driven by the transcription factor Tbx21 with minimal contribution from Eomes. This results in a CD8+ T cell phenotype that is long lived, and present in the peripheral organs in high numbers whilst retaining effector function.
- the antigen-specific inflating memory CD8+ T cells develop through one or more of processing, presentation and co-stimulation conditions.
- the processing of the epitope occurs independently of the proteasome or immunoproteasome and optionally presentation by a non-hematopoietic unconventional APC during the later stages can help to preserve this phenotype.
- a vector which encodes induces an inflating memory response.
- a recombinant polypeptide comprising one or more epitopes e.g., one or more T cell epitopes, e.g., one or more cancer-specific CD8+ epitopes, e.g., one or more cancer-specific CD8+ epitopes, each comprising an amino acid sequence as set forth in any of SEQ ID NOs: 1-35
- a polynucleotide encoding a recombinant polypeptide comprising one or more epitopes, e.g., one or more T cell epitopes, e.g., one or more cancer-specific CD8+ epitopes, e.g., one or more cancer-specific CD8+ epitopes, each comprising an amino acid sequence as set forth in any of SEQ ID NOs: 1-35 induces an inflating memory response.
- the present disclosure provides a composition, e.g., a therapeutic composition.
- the composition e.g., the therapeutic composition induces an inflating memory CD8+ T cell response (i.e., a sustained, functional, durable CD8+ T cell response).
- the resulting pool of CD8+ T cells are able to resist exhaustion which can occur due to prolonged TCR stimulation.
- the therapeutic composition comprises: (i) a recombinant polypeptide comprising a cancer-specific CD8+ T cell epitope, or (ii) a polynucleotide encoding a recombinant polypeptide comprising a cancer-specific CD8+ T cell epitope, (iii) a vector comprising (i) or (ii), (iv) antigen presenting cells (APCs) comprising (i), (ii), or (iii), or (v) T cells stimulated with APCs comprising (i), (ii), or (iii); wherein the cancer-specific CD8+ T cell epitope is GVYDGREHTV.
- APCs antigen presenting cells
- the therapeutic composition comprises: (i) a recombinant polypeptide consisting of a cancer-specific CD8+ T cell epitope, or (ii) a polynucleotide encoding a recombinant polypeptide consisting of a cancer-specific CD8+ T cell epitope, (iii) a vector comprising (i) or (ii), (iv) antigen presenting cells (APCs) comprising (i), (ii), or (iii), or (v) T cells stimulated with APCs comprising (i), (ii), or (iii); wherein the cancerspecific CD8+ T cell epitope is GVYDGREHTV.
- APCs antigen presenting cells
- the therapeutic composition comprises: (i) a recombinant polypeptide comprising a cancer-specific CD8+ T cell epitope, or (ii) a polynucleotide encoding a recombinant polypeptide comprising a cancerspecific CD8+ T cell epitope, (iii) a vector comprising (i) or (ii), (iv) antigen presenting cells (APCs) comprising (i), (ii), or (iii), or (v) T cells stimulated with APCs comprising (i), (ii), or
- cancer-specific CD8+ T cell epitope is GVYDGREHTV and wherein the composition is for use in treating cancer is a subject that expresses an MHC encoded by an HLA- A*02:01 allele.
- the therapeutic composition comprises: (i) a recombinant polypeptide consisting of a cancer-specific CD8+ T cell epitope, or (ii) a polynucleotide encoding a recombinant polypeptide consisting of a cancer-specific CD8+ T cell epitope, (iii) a vector comprising (i) or (ii), (iv) antigen presenting cells (APCs) comprising (i), (ii), or (iii), or (v) T cells stimulated with APCs comprising (i), (ii), or (iii); wherein the cancer-specific CD8+ T cell epitope is GVYDGREHTV and wherein the composition is for use in treating cancer is a subject that expresses an MHC encoded by an HLA-A*02:01 allele.
- APCs antigen presenting cells
- the therapeutic composition comprises: (i) a recombinant polypeptide comprising a cancer-specific CD8+ T cell epitope, or (ii) a polynucleotide encoding a recombinant polypeptide comprising a cancer-specific CD8+ T cell epitope, (iii) a vector comprising (i) or (ii), (iv) antigen presenting cells (APCs) comprising (i), (ii), or (iii), or (v) T cells stimulated with APCs comprising (i), (ii), or (iii); wherein the cancer-specific CD8+ T cell epitope is KLVELEHTL.
- APCs antigen presenting cells
- the therapeutic composition comprises: (i) a recombinant polypeptide consisting of a cancer-specific CD8+ T cell epitope, or (ii) a polynucleotide encoding a recombinant polypeptide consisting of a cancer-specific CD8+ T cell epitope, (iii) a vector comprising (i) or (ii), (iv) antigen presenting cells (APCs) comprising (i),
- the therapeutic composition comprises: (i) a recombinant polypeptide comprising a cancer-specific CD8+ T cell epitope, or (ii) a polynucleotide encoding a recombinant polypeptide comprising a cancerspecific CD8+ T cell epitope, (iii) a vector comprising (i) or (ii), (iv) antigen presenting cells (APCs) comprising (i), (ii), or (iii), or (v) T cells stimulated with APCs comprising (i), (ii), or
- the therapeutic composition comprises: (i) a recombinant polypeptide consisting of a cancer-specific CD8+ T cell epitope, or (ii) a polynucleotide encoding a recombinant polypeptide consisting of a cancer-specific CD8+ T cell epitope, (iii) a vector comprising (i) or (ii), (iv) antigen presenting cells (APCs) comprising (i), (ii), or (iii), or (v) T cells stimulated with APCs comprising (i), (ii), or (iii); wherein the cancer-specific CD8+ T cell epitope is KLVELEHTL and wherein the composition is for use in treating cancer is a subject
- the therapeutic composition comprises: (i) a recombinant polypeptide comprising a cancer-specific CD8+ T cell epitope, or (ii) a polynucleotide encoding a recombinant polypeptide comprising a cancer-specific CD8+ T cell epitope, (iii) a vector comprising (i) or (ii), (iv) antigen presenting cells (APCs) comprising (i), (ii), or (iii), or (v) T cells stimulated with APCs comprising (i), (ii), or (iii); wherein the cancer-specific CD8+ T cell epitope is SPSSASLAL.
- APCs antigen presenting cells
- the therapeutic composition comprises: (i) a recombinant polypeptide consisting of a cancer-specific CD8+ T cell epitope, or (ii) a polynucleotide encoding a recombinant polypeptide consisting of a cancer-specific CD8+ T cell epitope, (iii) a vector comprising (i) or (ii), (iv) antigen presenting cells (APCs) comprising (i),
- the therapeutic composition comprises: (i) a recombinant polypeptide comprising a cancer-specific CD8+ T cell epitope, or (ii) a polynucleotide encoding a recombinant polypeptide comprising a cancerspecific CD8+ T cell epitope, (iii) a vector comprising (i) or (ii), (iv) antigen presenting cells (APCs) comprising (i), (ii), or (iii), or (v) T cells stimulated with APCs comprising (i), (ii), or
- cancer-specific CD8+ T cell epitope is SPSSASLAL and wherein the composition is for use in treating cancer is a subject that expresses an MHC encoded by an HLA- B*07:02 allele and/or an HLA-B*35:03 allele.
- the therapeutic composition comprises: (i) a recombinant polypeptide consisting of a cancer-specific CD8+ T cell epitope, or (ii) a polynucleotide encoding a recombinant polypeptide consisting of a cancerspecific CD8+ T cell epitope, (iii) a vector comprising (i) or (ii), (iv) antigen presenting cells (APCs) comprising (i), (ii), or (iii), or (v) T cells stimulated with APCs comprising (i), (ii), or (iii); wherein the cancer-specific CD8+ T cell epitope is SPSSASLAL and wherein the composition is for use in treating cancer is a subject that expresses an MHC encoded by an HLA- B*07:02 allele and/or an HLA-B*35:03 allele.
- the therapeutic composition comprises: (i) a recombinant polypeptide comprising a cancer-specific CD8+ T cell epitope, or (ii) a polynucleotide encoding a recombinant polypeptide comprising a cancer-specific CD8+ T cell epitope, (iii) a vector comprising (i) or (ii), (iv) antigen presenting cells (APCs) comprising (i), (ii), or (iii), or (v) T cells stimulated with APCs comprising (i), (ii), or (iii); wherein the cancer-specific CD8+ T cell epitope is KPRPDVTNEL.
- APCs antigen presenting cells
- the therapeutic composition comprises: (i) a recombinant polypeptide consisting of a cancer-specific CD8+ T cell epitope, or (ii) a polynucleotide encoding a recombinant polypeptide consisting of a cancer-specific CD8+ T cell epitope, (iii) a vector comprising (i) or (ii), (iv) antigen presenting cells (APCs) comprising (i),
- the therapeutic composition comprises: (i) a recombinant polypeptide comprising a cancer-specific CD8+ T cell epitope, or (ii) a polynucleotide encoding a recombinant polypeptide comprising a cancerspecific CD8+ T cell epitope, (iii) a vector comprising (i) or (ii), (iv) antigen presenting cells (APCs) comprising (i), (ii), or (iii), or (v) T cells stimulated with APCs comprising (i), (ii), or
- cancer-specific CD8+ T cell epitope is KPRPDVTNEL and wherein the composition is for use in treating cancer is a subject that expresses an MHC encoded by an HLA- B*07:02 allele, an HLA-B*35:03 allele, an HLA-C*07:02 allele, or any combination thereof.
- the therapeutic composition comprises: (i) a recombinant polypeptide consisting of a cancer-specific CD8+ T cell epitope, or (ii) a polynucleotide encoding a recombinant polypeptide consisting of a cancer-specific CD8+ T cell epitope, (iii) a vector comprising (i) or (ii), (iv) antigen presenting cells (APCs) comprising (i), (ii), or (iii), or (v) T cells stimulated with APCs comprising (i), (ii), or (iii); wherein the cancer-specific CD8+ T cell epitope is KPRPDVTNEL and wherein the composition is for use in treating cancer is a subject that expresses an MHC encoded by an HLA-B*07:02 allele, an HLA-B*35:03 allele, an HLA- C*07:02 allele, or any combination thereof.
- the therapeutic composition comprises: (i) a recombinant polypeptide comprising a cancer-specific CD8+ T cell epitope, or (ii) a polynucleotide encoding a recombinant polypeptide comprising a cancer-specific CD8+ T cell epitope, (iii) a vector comprising (i) or (ii), (iv) antigen presenting cells (APCs) comprising (i), (ii), or (iii), or (v) T cells stimulated with APCs comprising (i), (ii), or (iii); wherein the cancer-specific CD8+ T cell epitope is KEFAFLEHSL.
- APCs antigen presenting cells
- the therapeutic composition comprises: (i) a recombinant polypeptide consisting of a cancer-specific CD8+ T cell epitope, or (ii) a polynucleotide encoding a recombinant polypeptide consisting of a cancer-specific CD8+ T cell epitope, (iii) a vector comprising (i) or (ii), (iv) antigen presenting cells (APCs) comprising (i), (ii), or (iii), or (v) T cells stimulated with APCs comprising (i), (ii), or (iii); wherein the cancerspecific CD8+ T cell epitope is KEFAFLEHSL.
- APCs antigen presenting cells
- the therapeutic composition comprises: (i) a recombinant polypeptide comprising a cancer-specific CD8+ T cell epitope, or (ii) a polynucleotide encoding a recombinant polypeptide comprising a cancerspecific CD8+ T cell epitope, (iii) a vector comprising (i) or (ii), (iv) antigen presenting cells (APCs) comprising (i), (ii), or (iii), or (v) T cells stimulated with APCs comprising (i), (ii), or (iii); wherein the cancer-specific CD8+ T cell epitope is KEFAFLEHSL and wherein the composition is for use in treating cancer is a subject that expresses an MHC encoded by an HLA- B*40:01 allele, an HLA-B*40:02 allele, an HLA-B*44:02 allele, or any combination thereof.
- the therapeutic composition comprises: (i) a recombinant polypeptide comprising a cancer-specific CD8+ T cell epitope, or (ii) a polynucleotide encoding a recombinant polypeptide comprising a cancer-specific CD8+ T cell epitope, (iii) a vector comprising (i) or (ii), (iv) antigen presenting cells (APCs) comprising (i), (ii), or (iii), or (v) T cells stimulated with APCs comprising (i), (ii), or (iii); wherein the cancer-specific CD8+ T cell epitope is KEFAFLEHSL and wherein the composition is for use in treating cancer is a subject that expresses an MHC encoded by an HLA-B*44:02 allele.
- APCs antigen presenting cells
- the therapeutic composition comprises: (i) a recombinant polypeptide consisting of a cancer-specific CD8+ T cell epitope, or (ii) a polynucleotide encoding a recombinant polypeptide consisting of a cancer-specific CD8+ T cell epitope, (iii) a vector comprising (i) or (ii), (iv) antigen presenting cells (APCs) comprising (i), (ii), or (iii), or (v) T cells stimulated with APCs comprising (i), (ii), or (iii); wherein the cancer-specific CD8+ T cell epitope is KEFAFLEHSL and wherein the composition is for use in treating cancer is a subject that expresses an MHC encoded by an HLA- B*40:01 allele, an HLA-B*40:02 allele, an HLA-B*44:02 allele, or any combination thereof.
- the therapeutic composition comprises: (i) a recombinant polypeptide consisting of a cancer-specific CD8+ T cell epitope, or (ii) a polynucleotide encoding a recombinant polypeptide consisting of a cancer-specific CD8+ T cell epitope, (iii) a vector comprising (i) or (ii), (iv) antigen presenting cells (APCs) comprising (i), (ii), or (iii), or (v) T cells stimulated with APCs comprising (i), (ii), or (iii); wherein the cancer-specific CD8+ T cell epitope is KEFAFLEHSL and wherein the composition is for use in treating cancer is a subject that expresses an MHC encoded by an HLA-B*44:02 allele.
- APCs antigen presenting cells
- the therapeutic composition comprises: (i) a recombinant polypeptide comprising a cancer-specific CD8+ T cell epitope, or (ii) a polynucleotide encoding a recombinant polypeptide comprising a cancer-specific CD8+ T cell epitope, (iii) a vector comprising (i) or (ii), (iv) antigen presenting cells (APCs) comprising (i), (ii), or (iii), or (v) T cells stimulated with APCs comprising (i), (ii), or (iii); wherein the cancer-specific CD8+ T cell epitope is HELGFKVVL.
- APCs antigen presenting cells
- the therapeutic composition comprises: (i) a recombinant polypeptide consisting of a cancer-specific CD8+ T cell epitope, or (ii) a polynucleotide encoding a recombinant polypeptide consisting of a cancer-specific CD8+ T cell epitope, (iii) a vector comprising (i) or (ii), (iv) antigen presenting cells (APCs) comprising (i),
- the therapeutic composition comprises: (i) a recombinant polypeptide comprising a cancer-specific CD8+ T cell epitope, or (ii) a polynucleotide encoding a recombinant polypeptide comprising a cancerspecific CD8+ T cell epitope, (iii) a vector comprising (i) or (ii), (iv) antigen presenting cells (APCs) comprising (i), (ii), or (iii), or (v) T cells stimulated with APCs comprising (i), (ii), or
- cancer-specific CD8+ T cell epitope is HELGFKVVL and wherein the composition is for use in treating cancer is a subject that expresses an MHC encoded by an HLA- B*18:01 allele.
- the therapeutic composition comprises: (i) a recombinant polypeptide comprising a cancer-specific CD8+ T cell epitope, or (ii) a polynucleotide encoding a recombinant polypeptide comprising a cancer-specific CD8+ T cell epitope, (iii) a vector comprising (i) or (ii), (iv) antigen presenting cells (APCs) comprising (i), (ii), or (iii), or (v) T cells stimulated with APCs comprising (i), (ii), or (iii); wherein the cancer-specific CD8+ T cell epitope is HELGFKVVL and wherein the composition is for use in treating cancer is a subject that expresses an MHC encoded by an HLA-B*40:01 allele.
- APCs antigen presenting cells
- the therapeutic composition comprises: (i) a recombinant polypeptide comprising a cancer-specific CD8+ T cell epitope, or (ii) a polynucleotide encoding a recombinant polypeptide comprising a cancer-specific CD8+ T cell epitope(iii) a vector comprising (i) or (ii), (iv) antigen presenting cells (APCs) comprising (i), (ii), or (iii), or (v) T cells stimulated with APCs comprising (i), (ii), or (iii); wherein the cancer-specific CD8+ T cell epitope is HELGFKVVL and wherein the composition is for use in treating cancer is a subject that expresses an MHC encoded by an HLA- B*44:02 allele.
- APCs antigen presenting cells
- the therapeutic composition comprises: (i) a recombinant polypeptide consisting of a cancer-specific CD8+ T cell epitope, or (ii) a polynucleotide encoding a recombinant polypeptide consisting of a cancer-specific CD8+ T cell epitope, (iii) a vector comprising (i) or (ii), (iv) antigen presenting cells (APCs) comprising (i), (ii), or (iii), or (v) T cells stimulated with APCs comprising (i), (ii), or (iii); wherein the cancer-specific CD8+ T cell epitope is HELGFKVVL and wherein the composition is for use in treating cancer is a subject that expresses an MHC encoded by an HLA-B* 18:01 allele.
- APCs antigen presenting cells
- the therapeutic composition comprises: (i) a recombinant polypeptide consisting of a cancer-specific CD8+ T cell epitope, or (ii) a polynucleotide encoding a recombinant polypeptide consisting of a cancer-specific CD8+ T cell epitope, (iii) a vector comprising (i) or (ii), (iv) antigen presenting cells (APCs) comprising (i), (ii), or (iii), or (v) T cells stimulated with APCs comprising (i), (ii), or (iii); wherein the cancer-specific CD8+ T cell epitope is HELGFKVVL and wherein the composition is for use in treating cancer is a subject that expresses an MHC encoded by an HLA- B*40:01 allele.
- APCs antigen presenting cells
- the therapeutic composition comprises: (i) a recombinant polypeptide consisting of a cancer-specific CD8+ T cell epitope, or (ii) a polynucleotide encoding a recombinant polypeptide consisting of a cancer-specific CD8+ T cell epitope, (iii) a vector comprising (i) or (ii), (iv) antigen presenting cells (APCs) comprising (i), (ii), or (iii), or (v) T cells stimulated with APCs comprising (i), (ii), or (iii); wherein the cancer-specific CD8+ T cell epitope is HELGFKVVL and wherein the composition is for use in treating cancer is a subject that expresses an MHC encoded by an HLA-B*44:02 allele.
- APCs antigen presenting cells
- the therapeutic composition comprises: (i) a recombinant polypeptide consisting of a cancer-specific CD8+ T cell epitope, or (ii) a polynucleotide encoding a recombinant polypeptide consisting of a cancer-specific CD8+ T cell epitope, (iii) a vector comprising (i) or (ii), (iv) antigen presenting cells (APCs) comprising (i), (ii), or (iii), or (v) T cells stimulated with APCs comprising (i), (ii), or (iii); wherein the cancer-specific CD8+ T cell epitope is HELGFKVVL and wherein the composition is for use in treating cancer is a subject that expresses an MHC encoded by an HLA- B*40:02 allele.
- APCs antigen presenting cells
- the therapeutic composition comprises: (i) a recombinant polypeptide comprising a cancer-specific CD8+ T cell epitope, or (ii) a polynucleotide encoding a recombinant polypeptide comprising a cancer-specific CD8+ T cell epitope, (iii) a vector comprising (i) or (ii), (iv) antigen presenting cells (APCs) comprising (i), (ii), or (iii), or (v) T cells stimulated with APCs comprising (i), (ii), or (iii); wherein the cancer-specific CD8+ T cell epitope is NLRPPTQEL.
- APCs antigen presenting cells
- the therapeutic composition comprises: (i) a recombinant polypeptide consisting of a cancer-specific CD8+ T cell epitope, or (ii) a polynucleotide encoding a recombinant polypeptide consisting of a cancer-specific CD8+ T cell epitope, (iii) a vector comprising (i) or (ii), (iv) antigen presenting cells (APCs) comprising (i),
- the therapeutic composition comprises: (i) a recombinant polypeptide comprising a cancer-specific CD8+ T cell epitope, or (ii) a polynucleotide encoding a recombinant polypeptide comprising a cancerspecific CD8+ T cell epitope, (iii) a vector comprising (i) or (ii), (iv) antigen presenting cells (APCs) comprising (i), (ii), or (iii), or (v) T cells stimulated with APCs comprising (i), (ii), or
- cancer-specific CD8+ T cell epitope is NLRPPTQEL and wherein the composition is for use in treating cancer is a subject that expresses an MHC encoded by an HLA- B*07:02 allele, an HLA-B*35:03 allele, an HLA-C*07:02 allele, an HLA-C*03:03 allele, or any combination thereof.
- the therapeutic composition comprises: (i) a recombinant polypeptide consisting of a cancer-specific CD8+ T cell epitope, or (ii) a polynucleotide encoding a recombinant polypeptide consisting of a cancer-specific CD8+ T cell epitope, (iii) a vector comprising (i) or (ii), (iv) antigen presenting cells (APCs) comprising (i), (ii), or (iii), or (v) T cells stimulated with APCs comprising (i), (ii), or (iii); wherein the cancerspecific CD8+ T cell epitope is NLRPPTQEL and wherein the composition is for use in treating cancer is a subject that expresses an MHC encoded by an HLA-B*07:02 allele, an HLA-B*35:03 allele, an HLA-C*07:02 allele, an HLA-C*03:03 allele, or any combination thereof
- the therapeutic composition comprises: (i) a recombinant polypeptide comprising at least two cancer-specific CD8+ T cell epitopes, or (ii) a polynucleotide encoding a recombinant polypeptide comprising at least two cancer-specific CD8+ T cell epitopes, (iii) a vector comprising (i) or (ii), (iv) antigen presenting cells (APCs) comprising (i), (ii), or (iii), or (v) T cells stimulated with APCs comprising (i), (ii), or (iii); wherein the at least two cancer-specific CD8+ T cell epitopes are GVYDGREHTV and KLVELEHTL.
- APCs antigen presenting cells
- the therapeutic composition comprises: (i) a recombinant polypeptide consisting of at least two cancer-specific CD8+ T cell epitopes, or (ii) a polynucleotide encoding a recombinant polypeptide consisting of at least two cancer-specific CD8+ T cell epitopes, (iii) a vector comprising (i) or (ii), (iv) antigen presenting cells (APCs) comprising (i), (ii), or (iii), or (v) T cells stimulated with APCs comprising (i), (ii), or (iii); wherein the at least two cancerspecific CD8+ T cell epitopes are GVYDGREHTV and KLVELEHTL.
- APCs antigen presenting cells
- the therapeutic composition comprises: (i) a recombinant polypeptide comprising at least two cancer-specific CD8+ T cell epitopes, or (ii) a polynucleotide encoding a recombinant polypeptide comprising at least two cancer-specific CD8+ T cell epitopes, (iii) a vector comprising (i) or (ii), (iv) antigen presenting cells (APCs) comprising (i), (ii), or (iii), or (v) T cells stimulated with APCs comprising (i), (ii), or (iii); wherein the at least two cancer-specific CD8+ T cell epitopes are GVYDGREHTV and KLVELEHTL and wherein the composition is for use in treating cancer is a subject that expresses an MHC encoded by an HLA-A*02:01 allele.
- APCs antigen presenting cells
- the therapeutic composition comprises: (i) a recombinant polypeptide consisting of at least two cancer-specific CD8+ T cell epitopes, or (ii) a polynucleotide encoding a recombinant polypeptide consisting of at least two cancer-specific CD8+ T cell epitopes, (iii) a vector comprising (i) or (ii), (iv) antigen presenting cells (APCs) comprising (i), (ii), or (iii), or (v) T cells stimulated with APCs comprising (i), (ii), or (iii); wherein the at least two cancerspecific CD8+ T cell epitopes are GVYDGREHTV and KLVELEHTL and wherein the composition is for use in treating cancer is a subject that expresses an MHC encoded by an HLA- A*02:01 allele.
- APCs antigen presenting cells
- the therapeutic composition comprises: (i) a recombinant polypeptide comprising at least two cancer-specific CD8+ T cell epitopes, or (ii) a polynucleotide encoding a recombinant polypeptide comprising at least two cancer-specific CD8+ T cell epitopes, (iii) a vector comprising (i) or (ii), (iv) antigen presenting cells (APCs) comprising (i), (ii), or (iii), or (v) T cells stimulated with APCs comprising (i), (ii), or (iii); wherein the at least two cancer-specific CD8+ T cell epitopes are GVYDGREHTV and SPSSASLAL.
- APCs antigen presenting cells
- the therapeutic composition comprises: (i) a recombinant polypeptide consisting of at least two cancer-specific CD8+ T cell epitopes, or (ii) a polynucleotide encoding a recombinant polypeptide consisting of at least two cancer-specific CD8+ T cell epitopes, (iii) a vector comprising (i) or (ii), (iv) antigen presenting cells (APCs) comprising (i), (ii), or (iii), or (v) T cells stimulated with APCs comprising (i), (ii), or (iii); wherein the at least two cancerspecific CD8+ T cell epitopes are GVYDGREHTV and SPSSASLAL.
- APCs antigen presenting cells
- the therapeutic composition comprises: (i) a recombinant polypeptide comprising at least two cancer-specific CD8+ T cell epitopes, or (ii) a polynucleotide encoding a recombinant polypeptide comprising at least two cancer-specific CD8+ T cell epitopes, (iii) a vector comprising (i) or (ii), (iv) antigen presenting cells (APCs) comprising (i), (ii), or (iii), or (v) T cells stimulated with APCs comprising (i), (ii), or (iii); wherein the at least two cancer-specific CD8+ T cell epitopes are GVYDGREHTV and SPSSASLAL and wherein the composition is for use in treating cancer is a subject that expresses an MHC encoded by an HLA-A*02:01 allele, an HLA-B*07:02 allele, an HLA-B*35:03 allele, or any combination
- the therapeutic composition comprises: (i) a recombinant polypeptide consisting of at least two cancer-specific CD8+ T cell epitopes, or (ii) a polynucleotide encoding a recombinant polypeptide consisting of at least two cancer-specific CD8+ T cell epitopes, (iii) a vector comprising (i) or (ii), (iv) antigen presenting cells (APCs) comprising (i), (ii), or (iii), or (v) T cells stimulated with APCs comprising (i), (ii), or (iii); wherein the at least two cancerspecific CD8+ T cell epitopes are GVYDGREHTV and SPSSASLAL and wherein the composition is for use in treating cancer is a subject that expresses an MHC encoded by an HLA- A*02:01 allele, an HLA-B*07:02 allele, an HLA-B*35:03 allele, or any
- the therapeutic composition comprises: (i) a recombinant polypeptide comprising at least two cancer-specific CD8+ T cell epitopes, or (ii) a polynucleotide encoding a recombinant polypeptide comprising at least two cancer-specific CD8+ T cell epitopes, (iii) a vector comprising (i) or (ii), (iv) antigen presenting cells (APCs) comprising (i), (ii), or (iii), or (v) T cells stimulated with APCs comprising (i), (ii), or (iii); wherein the at least two cancer-specific CD8+ T cell epitopes are GVYDGREHTV and KPRPDVTNEL.
- APCs antigen presenting cells
- the therapeutic composition comprises: (i) a recombinant polypeptide consisting of at least two cancer-specific CD8+ T cell epitopes, or (ii) a polynucleotide encoding a recombinant polypeptide consisting of at least two cancer-specific CD8+ T cell epitopes, (iii) a vector comprising (i) or (ii), (iv) antigen presenting cells (APCs) comprising (i), (ii), or (iii), or (v) T cells stimulated with APCs comprising (i), (ii), or (iii); wherein the at least two cancerspecific CD8+ T cell epitopes are GVYDGREHTV and KPRPDVTNEL.
- APCs antigen presenting cells
- the therapeutic composition comprises: (i) a recombinant polypeptide comprising at least two cancer-specific CD8+ T cell epitopes, or (ii) a polynucleotide encoding a recombinant polypeptide comprising at least two cancer-specific CD8+ T cell epitopes, (iii) a vector comprising (i) or (ii), (iv) antigen presenting cells (APCs) comprising (i), (ii), or (iii), or (v) T cells stimulated with APCs comprising (i), (ii), or (iii); wherein the at least two cancer-specific CD8+ T cell epitopes are GVYDGREHTV and KPRPDVTNEL and wherein the composition is for use in treating cancer is a subject that expresses an MHC encoded by an HLA-A*02:01 allele, an HLA-B*07:02 allele, an HLA-B*35:03 allele, an
- the therapeutic composition comprises: (i) a recombinant polypeptide consisting of at least two cancer-specific CD8+ T cell epitopes, or (ii) a polynucleotide encoding a recombinant polypeptide consisting of at least two cancer-specific CD8+ T cell epitopes, (iii) a vector comprising (i) or (ii), (iv) antigen presenting cells (APCs) comprising (i), (ii), or (iii), or (v) T cells stimulated with APCs comprising (i), (ii), or (iii); wherein the at least two cancer-specific CD8+ T cell epitopes are GVYDGREHTV and KPRPDVTNEL and wherein the composition is for use in treating cancer is a subject that expresses an MHC encoded by an HLA-A*02:01 allele, an HLA-B*07:02 allele, an HLA- B*35:03 allele
- the therapeutic composition comprises: (i) a recombinant polypeptide comprising at least two cancer-specific CD8+ T cell epitopes, or (ii) a polynucleotide encoding a recombinant polypeptide comprising at least two cancer-specific CD8+ T cell epitopes, (iii) a vector comprising (i) or (ii), (iv) antigen presenting cells (APCs) comprising (i), (ii), or (iii), or (v) T cells stimulated with APCs comprising (i), (ii), or (iii); wherein the at least two cancer-specific CD8+ T cell epitopes are GVYDGREHTV and KEFAFLEHSL.
- APCs antigen presenting cells
- the therapeutic composition comprises: (i) a recombinant polypeptide consisting of at least two cancer-specific CD8+ T cell epitopes, or (ii) a polynucleotide encoding a recombinant polypeptide consisting of at least two cancer-specific CD8+ T cell epitopes, (iii) a vector comprising (i) or (ii), (iv) antigen presenting cells (APCs) comprising (i), (ii), or (iii), or (v) T cells stimulated with APCs comprising (i), (ii), or (iii); wherein the at least two cancerspecific CD8+ T cell epitopes are GVYDGREHTV and KEFAFLEHSL.
- APCs antigen presenting cells
- the therapeutic composition comprises: (i) a recombinant polypeptide comprising at least two cancer-specific CD8+ T cell epitopes, or (ii) a polynucleotide encoding a recombinant polypeptide comprising at least two cancer-specific CD8+ T cell epitopes, (iii) a vector comprising (i) or (ii), (iv) antigen presenting cells (APCs) comprising (i), (ii), or (iii), or (v) T cells stimulated with APCs comprising (i), (ii), or (iii); wherein the at least two cancer-specific CD8+ T cell epitopes are GVYDGREHTV and KEFAFLEHSL and wherein the composition is for use in treating cancer is a subject that expresses an MHC encoded by an HLA-A*02:01 allele, an HLA-B*40:01 allele, an HLA-B*44:02 allele, an
- the therapeutic composition comprises: (i) a recombinant polypeptide consisting of at least two cancer-specific CD8+ T cell epitopes, or (ii) a polynucleotide encoding a recombinant polypeptide consisting of at least two cancer-specific CD8+ T cell epitopes, (iii) a vector comprising (i) or (ii), (iv) antigen presenting cells (APCs) comprising (i), (ii), or (iii), or (v) T cells stimulated with APCs comprising (i), (ii), or (iii); wherein the at least two cancer-specific CD8+ T cell epitopes are GVYDGREHTV and KEFAFLEHSL and wherein the composition is for use in treating cancer is a subject that expresses an MHC encoded by an HLA-A*02:01 allele, an HLA-B*40:01 allele, an HLA- B*44:02 allele
- the therapeutic composition comprises: (i) a recombinant polypeptide comprising at least two cancer-specific CD8+ T cell epitopes, or (ii) a polynucleotide encoding a recombinant polypeptide comprising at least two cancer-specific CD8+ T cell epitopes, (iii) a vector comprising (i) or (ii), (iv) antigen presenting cells (APCs) comprising (i), (ii), or (iii), or (v) T cells stimulated with APCs comprising (i), (ii), or (iii); wherein the at least two cancer-specific CD8+ T cell epitopes are GVYDGREHTV and HELGFKVVL.
- the therapeutic composition comprises: (i) a recombinant polypeptide consisting of at least two cancer-specific CD8+ T cell epitopes, or (ii) a polynucleotide encoding a recombinant polypeptide consisting of at least two cancer-specific CD8+ T cell epitopes, (iii) a vector comprising (i) or (ii), (iv) antigen presenting cells (APCs) comprising (i), (ii), or (iii), or (v) T cells stimulated with APCs comprising (i), (ii), or (iii); wherein the at least two cancerspecific CD8+ T cell epitopes are GVYDGREHTV and HELGFKVVL.
- the therapeutic composition comprises: (i) a recombinant polypeptide comprising at least two cancer-specific CD8+ T cell epitopes, or (ii) a polynucleotide encoding a recombinant polypeptide comprising at least two cancer-specific CD8+ T cell epitopes, (iii) a vector comprising (i) or (ii), (iv) antigen presenting cells (APCs) comprising (i), (ii), or (iii), or (v) T cells stimulated with APCs comprising (i), (ii), or (iii); wherein the at least two cancer-specific CD8+ T cell epitopes are GVYDGREHTV and HELGFKVVL and wherein the composition is for use in treating cancer is a subject that expresses an MHC encoded by an HLA-A*02:01 allele, an HLA-B* 18:01 allele an HLA-B*40:01 allele, an
- the therapeutic composition comprises: (i) a recombinant polypeptide consisting of at least two cancer-specific CD8+ T cell epitopes, or (ii) a polynucleotide encoding a recombinant polypeptide consisting of at least two cancer-specific CD8+ T cell epitopes, (iii) a vector comprising (i) or (ii), (iv) antigen presenting cells (APCs) comprising (i), (ii), or (iii), or (v) T cells stimulated with APCs comprising (i), (ii), or (iii); wherein the at least two cancer-specific CD8+ T cell epitopes are GVYDGREHTV and HELGFKVVL and wherein the composition is for use in treating cancer is a subject that expresses an MHC encoded by an HLA-A*02:01 allele, an HLA-B*18:01 allele, an HLA- B*40:01 all
- the therapeutic composition comprises: (i) a recombinant polypeptide comprising at least two cancer-specific CD8+ T cell epitopes, or (ii) a polynucleotide encoding a recombinant polypeptide comprising at least two cancer-specific CD8+ T cell epitopes, (iii) a vector comprising (i) or (ii), (iv) antigen presenting cells (APCs) comprising (i), (ii), or (iii), or (v) T cells stimulated with APCs comprising (i), (ii), or (iii); wherein the at least two cancer-specific CD8+ T cell epitopes are KLVELEHTL and SPSSASLAL.
- APCs antigen presenting cells
- the therapeutic composition comprises: (i) a recombinant polypeptide consisting of at least two cancer-specific CD8+ T cell epitopes, or (ii) a polynucleotide encoding a recombinant polypeptide consisting of at least two cancer-specific CD8+ T cell epitopes, (iii) a vector comprising (i) or (ii), (iv) antigen presenting cells (APCs) comprising (i), (ii), or (iii), or (v) T cells stimulated with APCs comprising (i), (ii), or (iii); wherein the at least two cancerspecific CD8+ T cell epitopes are KLVELEHTL and SPSSASLAL.
- APCs antigen presenting cells
- the therapeutic composition comprises: (i) a recombinant polypeptide comprising at least two cancerspecific CD8+ T cell epitopes, or (ii) a polynucleotide encoding a recombinant polypeptide comprising at least two cancer-specific CD8+ T cell epitopes, (iii) a vector comprising (i) or (ii), (iv) antigen presenting cells (APCs) comprising (i), (ii), or (iii), or (v) T cells stimulated with APCs comprising (i), (ii), or (iii); wherein the at least two cancer-specific CD8+ T cell epitopes are KLVELEHTL and SPSSASLAL and wherein the composition is for use in treating cancer is a subject that expresses an MHC encoded by an HLA-A*02:01 allele, an HLA-B*07:02 allele, an HLA-B*35:03 allele, or any combination thereof.
- the therapeutic composition comprises: (i) a recombinant polypeptide consisting of at least two cancer-specific CD8+ T cell epitopes, or (ii) a polynucleotide encoding a recombinant polypeptide consisting of at least two cancer-specific CD8+ T cell epitopes, (iii) a vector comprising (i) or (ii), (iv) antigen presenting cells (APCs) comprising (i), (ii), or (iii), or (v) T cells stimulated with APCs comprising (i), (ii), or (iii); wherein the at least two cancer-specific CD8+ T cell epitopes are KLVELEHTL and SPSSASLAL and wherein the composition is for use in treating cancer is a subject that expresses an MHC encoded by an HLA-A*02:01 allele, an HLA-B*07:02 allele, an HLA-B*35:03 allele, or any combination
- the therapeutic composition comprises: (i) a recombinant polypeptide comprising at least two cancer-specific CD8+ T cell epitopes, or (ii) a polynucleotide encoding a recombinant polypeptide comprising at least two cancer-specific CD8+ T cell epitopes, (iii) a vector comprising (i) or (ii), (iv) antigen presenting cells (APCs) comprising (i), (ii), or (iii), or (v) T cells stimulated with APCs comprising (i), (ii), or (iii); wherein the at least two cancer-specific CD8+ T cell epitopes are KLVELEHTL and KPRPDVTNEL.
- APCs antigen presenting cells
- the therapeutic composition comprises: (i) a recombinant polypeptide consisting of at least two cancer-specific CD8+ T cell epitopes, or (ii) a polynucleotide encoding a recombinant polypeptide consisting of at least two cancer-specific CD8+ T cell epitopes, (iii) a vector comprising (i) or (ii), (iv) antigen presenting cells (APCs) comprising (i), (ii), or (iii), or (v) T cells stimulated with APCs comprising (i), (ii), or (iii); wherein the at least two cancerspecific CD8+ T cell epitopes are KLVELEHTL and KPRPDVTNEL.
- APCs antigen presenting cells
- the therapeutic composition comprises: (i) a recombinant polypeptide comprising at least two cancer-specific CD8+ T cell epitopes, or (ii) a polynucleotide encoding a recombinant polypeptide comprising at least two cancer-specific CD8+ T cell epitopes, (iii) a vector comprising (i) or (ii), (iv) antigen presenting cells (APCs) comprising (i), (ii), or (iii), or (v) T cells stimulated with APCs comprising (i), (ii), or (iii); wherein the at least two cancer-specific CD8+ T cell epitopes are KLVELEHTL and KPRPDVTNEL and wherein the composition is for use in treating cancer is a subject that expresses an MHC encoded by an HLA-A*02:01 allele, an HLA-B*07:02 allele, an HLA-B*35:03 allele, an HLA
- the therapeutic composition comprises: (i) a recombinant polypeptide consisting of at least two cancer-specific CD8+ T cell epitopes, or (ii) a polynucleotide encoding a recombinant polypeptide consisting of at least two cancer-specific CD8+ T cell epitopes, (iii) a vector comprising (i) or (ii), (iv) antigen presenting cells (APCs) comprising (i), (ii), or (iii), or (v) T cells stimulated with APCs comprising (i), (ii), or (iii); wherein the at least two cancer-specific CD8+ T cell epitopes are KLVELEHTL and KPRPDVTNEL and wherein the composition is for use in treating cancer is a subject that expresses an MHC encoded by an HLA-A*02:01 allele, an HLA-B*07:02 allele, an HLA- B*35:03 allele, an
- the therapeutic composition comprises: (i) a recombinant polypeptide comprising at least two cancer-specific CD8+ T cell epitopes, or (ii) a polynucleotide encoding a recombinant polypeptide comprising at least two cancer-specific CD8+ T cell epitopes, (iii) a vector comprising (i) or (ii), (iv) antigen presenting cells (APCs) comprising (i), (ii), or (iii), or (v) T cells stimulated with APCs comprising (i), (ii), or (iii); wherein the at least two cancer-specific CD8+ T cell epitopes are KLVELEHTL and KEFAFLEHSL.
- the therapeutic composition comprises: (i) a recombinant polypeptide consisting of at least two cancer-specific CD8+ T cell epitopes, or (ii) a polynucleotide encoding a recombinant polypeptide consisting of at least two cancer-specific CD8+ T cell epitopes, (iii) a vector comprising (i) or (ii), (iv) antigen presenting cells (APCs) comprising (i), (ii), or (iii), or (v) T cells stimulated with APCs comprising (i), (ii), or (iii); wherein the at least two cancerspecific CD8+ T cell epitopes are KLVELEHTL and KEFAFLEHSL.
- APCs antigen presenting cells
- the therapeutic composition comprises: (i) a recombinant polypeptide comprising at least two cancerspecific CD8+ T cell epitopes, or (ii) a polynucleotide encoding a recombinant polypeptide comprising at least two cancer-specific CD8+ T cell epitopes, (iii) a vector comprising (i) or (ii),
- antigen presenting cells comprising (i), (ii), or (iii), or (v) T cells stimulated with APCs comprising (i), (ii), or (iii); wherein the at least two cancer-specific CD8+ T cell epitopes are KLVELEHTL and KEFAFLEHSL and wherein the composition is for use in treating cancer is a subject that expresses an MHC encoded by an HLA-A*02:01 allele, an HLA-B*40:01 allele, an HLA-B*44:02 allele, an HLA-B*40:02 allele, or any combination thereof.
- the therapeutic composition comprises: (i) a recombinant polypeptide consisting of at least two cancer-specific CD8+ T cell epitopes, or (ii) a polynucleotide encoding a recombinant polypeptide consisting of at least two cancer-specific CD8+ T cell epitopes, (iii) a vector comprising (i) or (ii), (iv) antigen presenting cells (APCs) comprising (i), (ii), or (iii), or
- T cells stimulated with APCs comprising (i), (ii), or (iii); wherein the at least two cancerspecific CD8+ T cell epitopes are KLVELEHTL and KEFAFLEHSL and wherein the composition is for use in treating cancer is a subject that expresses an MHC encoded by an HLA- A*02:01 allele, an HLA-B*40:01 allele, an HLA-B*44:02 allele, an HLA-B*40:02 allele, or any combination thereof.
- the therapeutic composition comprises: (i) a recombinant polypeptide comprising at least two cancer-specific CD8+ T cell epitopes, or (ii) a polynucleotide encoding a recombinant polypeptide comprising at least two cancer-specific CD8+ T cell epitopes, (iii) a vector comprising (i) or (ii), (iv) antigen presenting cells (APCs) comprising (i), (ii), or (iii), or (v) T cells stimulated with APCs comprising (i), (ii), or (iii); wherein the at least two cancer-specific CD8+ T cell epitopes are KLVELEHTL and HELGFKVVL.
- the therapeutic composition comprises: (i) a recombinant polypeptide consisting of at least two cancer-specific CD8+ T cell epitopes, or (ii) a polynucleotide encoding a recombinant polypeptide consisting of at least two cancer-specific CD8+ T cell epitopes, (iii) a vector comprising (i) or (ii), (iv) antigen presenting cells (APCs) comprising (i), (ii), or (iii), or (v) T cells stimulated with APCs comprising (i), (ii), or (iii); wherein the at least two cancerspecific CD8+ T cell epitopes are KLVELEHTL and HELGFKVVL.
- the therapeutic composition comprises: (i) a recombinant polypeptide comprising at least two cancerspecific CD8+ T cell epitopes, or (ii) a polynucleotide encoding a recombinant polypeptide comprising at least two cancer-specific CD8+ T cell epitopes, (iii) a vector comprising (i) or (ii), (iv) antigen presenting cells (APCs) comprising (i), (ii), or (iii), or (v) T cells stimulated with APCs comprising (i), (ii), or (iii); wherein the at least two cancer-specific CD8+ T cell epitopes are KLVELEHTL and HELGFKVVL and wherein the composition is for use in treating cancer is a subject that expresses an MHC encoded by an HLA-A*02:01 allele, an HLA-B*18:01 allele, an HLA-B*40:01 allele, an HLA
- the therapeutic composition comprises: (i) a recombinant polypeptide consisting of at least two cancer-specific CD8+ T cell epitopes, or (ii) a polynucleotide encoding a recombinant polypeptide consisting of at least two cancer-specific CD8+ T cell epitopes, (iii) a vector comprising (i) or (ii), (iv) antigen presenting cells (APCs) comprising (i), (ii), or (iii), or (v) T cells stimulated with APCs comprising (i), (ii), or (iii); wherein the at least two cancer-specific CD8+ T cell epitopes are KLVELEHTL and HELGFKVVL and wherein the composition is for use in treating cancer is a subject that expresses an MHC encoded by an HLA-A*02:01 allele, an HLA-B*18:01 allele, an HLA- B*40:01 allele,
- the therapeutic composition comprises: (i) a recombinant polypeptide comprising at least two cancer-specific CD8+ T cell epitopes, or (ii) a polynucleotide encoding a recombinant polypeptide comprising at least two cancer-specific CD8+ T cell epitopes, (iii) a vector comprising (i) or (ii), (iv) antigen presenting cells (APCs) comprising (i), (ii), or (iii), or (v) T cells stimulated with APCs comprising (i), (ii), or (iii); wherein the at least two cancer-specific CD8+ T cell epitopes are SPSSASLAL and KPRPDVTNEL.
- APCs antigen presenting cells
- the therapeutic composition comprises: (i) a recombinant polypeptide consisting of at least two cancer-specific CD8+ T cell epitopes, or (ii) a polynucleotide encoding a recombinant polypeptide consisting of at least two cancer-specific CD8+ T cell epitopes, (iii) a vector comprising (i) or (ii), (iv) antigen presenting cells (APCs) comprising (i), (ii), or (iii), or (v) T cells stimulated with APCs comprising (i), (ii), or (iii); wherein the at least two cancerspecific CD8+ T cell epitopes are SPSSASLAL and KPRPDVTNEL.
- APCs antigen presenting cells
- the therapeutic composition comprises: (i) a recombinant polypeptide comprising at least two cancerspecific CD8+ T cell epitopes, or (ii) a polynucleotide encoding a recombinant polypeptide comprising at least two cancer-specific CD8+ T cell epitopes, (iii) a vector comprising (i) or (ii),
- antigen presenting cells comprising (i), (ii), or (iii), or (v) T cells stimulated with APCs comprising (i), (ii), or (iii); wherein the at least two cancer-specific CD8+ T cell epitopes are SPSSASLAL and KPRPDVTNEL and wherein the composition is for use in treating cancer is a subject that expresses an MHC encoded by an HLA-B*07:02 allele, an HLA-B*35:03 allele, an HLA-C*07:02 allele, or any combination thereof.
- the therapeutic composition comprises: (i) a recombinant polypeptide consisting of at least two cancer-specific CD8+ T cell epitopes or (ii) a polynucleotide encoding a recombinant polypeptide consisting of at least two cancer-specific CD8+ T cell epitopes, (iii) a vector comprising (i) or (ii), (iv) antigen presenting cells (APCs) comprising (i), (ii), or (iii), or (v) T cells stimulated with APCs comprising (i), (ii), or (iii); wherein the at least two cancer-specific CD8+ T cell epitopes are SPSSASLAL and KPRPDVTNEL and wherein the composition is for use in treating cancer is a subject that expresses an MHC encoded by an HLA-B*07:02 allele, an HLA-B*35:03 allele, an HLA-C*07:02 allele, or any combination
- the therapeutic composition comprises: (i) a recombinant polypeptide comprising at least two cancer-specific CD8+ T cell epitopes, or (ii) a polynucleotide encoding a recombinant polypeptide comprising at least two cancer-specific CD8+ T cell epitopes, (iii) a vector comprising (i) or (ii), (iv) antigen presenting cells (APCs) comprising (i), (ii), or (iii), or (v) T cells stimulated with APCs comprising (i), (ii), or (iii); wherein the at least two cancer-specific CD8+ T cell epitopes are SPSSASLAL and KEFAFLEHSL.
- APCs antigen presenting cells
- the therapeutic composition comprises: (i) a recombinant polypeptide consisting of at least two cancer-specific CD8+ T cell epitopes, or (ii) a polynucleotide encoding a recombinant polypeptide consisting of at least two cancer-specific CD8+ T cell epitopes, (iii) a vector comprising (i) or (ii), (iv) antigen presenting cells (APCs) comprising (i), (ii), or (iii), or
- the therapeutic composition comprises: (i) a recombinant polypeptide comprising at least two cancerspecific CD8+ T cell epitopes, or (ii) a polynucleotide encoding a recombinant polypeptide comprising at least two cancer-specific CD8+ T cell epitopes, (iii) a vector comprising (i) or (ii),
- antigen presenting cells comprising (i), (ii), or (iii), or (v) T cells stimulated with APCs comprising (i), (ii), or (iii); wherein the at least two cancer-specific CD8+ T cell epitopes are SPSSASLAL and KEFAFLEHSL and wherein the composition is for use in treating cancer is a subject that expresses an MHC encoded by an HLA-B*07:02 allele, an HLA-B*35:03 allele, an HLA-B*40:01 allele, an HLA-B*44:02 allele, an HLA-B*40:02 allele, or any combination thereof.
- the therapeutic composition comprises: (i) a recombinant polypeptide consisting of at least two cancer-specific CD8+ T cell epitopes, or (ii) a polynucleotide encoding a recombinant polypeptide consisting of at least two cancer-specific CD8+ T cell epitopes, (iii) a vector comprising (i) or (ii), (iv) antigen presenting cells (APCs) comprising (i), (ii), or (iii), or (v) T cells stimulated with APCs comprising (i), (ii), or (iii); wherein the at least two cancer-specific CD8+ T cell epitopes are SPSSASLAL and KEFAFLEHSL and wherein the composition is for use in treating cancer is a subject that expresses an MHC encoded by an HLA-B*07:02 allele, an HLA-B*35:03 allele, an HLA- B*40:01 allele, an H
- the therapeutic composition comprises: (i) a recombinant polypeptide comprising at least two cancer-specific CD8+ T cell epitopes, or (ii) a polynucleotide encoding a recombinant polypeptide comprising at least two cancer-specific CD8+ T cell epitopes, (iii) a vector comprising (i) or (ii), (iv) antigen presenting cells (APCs) comprising (i), (ii), or (iii), or (v) T cells stimulated with APCs comprising (i), (ii), or (iii); wherein the at least two cancer-specific CD8+ T cell epitopes are SPSSASLAL and HELGFKVVL.
- APCs antigen presenting cells
- the therapeutic composition comprises: (i) a recombinant polypeptide consisting of at least two cancer-specific CD8+ T cell epitopes, or (ii) a polynucleotide encoding a recombinant polypeptide consisting of at least two cancer-specific CD8+ T cell epitopes, (iii) a vector comprising (i) or (ii), (iv) antigen presenting cells (APCs) comprising (i), (ii), or (iii), or
- the therapeutic composition comprises: (i) a recombinant polypeptide comprising at least two cancerspecific CD8+ T cell epitopes, or (ii) a polynucleotide encoding a recombinant polypeptide comprising at least two cancer-specific CD8+ T cell epitopes, (iii) a vector comprising (i) or (ii), (iv) antigen presenting cells (APCs) comprising (i), (ii), or (iii), or (v) T cells stimulated with APCs comprising (i), (ii), or (iii); wherein the at least two cancer-specific CD8+ T cell epitopes are SPSSASLAL and HELGFKVVL and wherein the composition is for use
- the therapeutic composition comprises: (i) a recombinant polypeptide consisting of at least two cancer-specific CD8+ T cell epitopes, or (ii) a polynucleotide encoding a recombinant polypeptide consisting of at least two cancer-specific CD8+ T cell epitopes, (iii) a vector comprising (i) or (ii), (iv) antigen presenting cells (APCs) comprising (i), (ii), or (iii), or (v) T cells stimulated with APCs comprising (i), (ii), or (iii); wherein the at least two cancer-specific CD8+ T cell epitopes are SPSSASLAL and HELGFKVVL and wherein the composition is for use in treating cancer is a subject that expresses an MHC encoded by an HLA-B*07:02 allele, an HLA-B*35:03 allele, an HLA- B* 18:01 allele, an
- the therapeutic composition comprises: (i) a recombinant polypeptide comprising at least two cancer-specific CD8+ T cell epitopes, or (ii) a polynucleotide encoding a recombinant polypeptide comprising at least two cancer-specific CD8+ T cell epitopes, (iii) a vector comprising (i) or (ii), (iv) antigen presenting cells (APCs) comprising (i), (ii), or (iii), or (v) T cells stimulated with APCs comprising (i), (ii), or (iii); wherein the at least two cancer-specific CD8+ T cell epitopes are KPRPDVTNEL and KEFAFLEHSL.
- APCs antigen presenting cells
- the therapeutic composition comprises: (i) a recombinant polypeptide consisting of at least two cancer-specific CD8+ T cell epitopes, or (ii) a polynucleotide encoding a recombinant polypeptide consisting of at least two cancer-specific CD8+ T cell epitopes, (iii) a vector comprising (i) or (ii), (iv) antigen presenting cells (APCs) comprising (i), (ii), or (iii), or (v) T cells stimulated with APCs comprising (i), (ii), or (iii); wherein the at least two cancerspecific CD8+ T cell epitopes are KPRPDVTNEL and KEFAFLEHSL.
- APCs antigen presenting cells
- the therapeutic composition comprises: (i) a recombinant polypeptide comprising at least two cancer-specific CD8+ T cell epitopes, or (ii) a polynucleotide encoding a recombinant polypeptide comprising at least two cancer-specific CD8+ T cell epitopes, (iii) a vector comprising (i) or (ii), (iv) antigen presenting cells (APCs) comprising (i), (ii), or (iii), or (v) T cells stimulated with APCs comprising (i), (ii), or (iii); wherein the at least two cancer-specific CD8+ T cell epitopes are KPRPDVTNEL and KEFAFLEHSL and wherein the composition is for use in treating cancer is a subject that expresses an MHC encoded by an HLA-B*07:02 allele, an HLA-B*40:01 allele, an HLA-B*44:02 allele, an H
- the therapeutic composition comprises: (i) a recombinant polypeptide consisting of at least two cancer-specific CD8+ T cell epitopes, or (ii) a polynucleotide encoding a recombinant polypeptide consisting of at least two cancer-specific CD8+ T cell epitopes, (iii) a vector comprising (i) or (ii), (iv) antigen presenting cells (APCs) comprising (i), (ii), or (iii), or (v) T cells stimulated with APCs comprising (i), (ii), or (iii); wherein the at least two cancer-specific CD8+ T cell epitopes are KPRPDVTNEL and KEFAFLEHSL and wherein the composition is for use in treating cancer is a subject that expresses an MHC encoded by an HLA-B*07:02 allele, an HLA-B*40:01 allele, an HLA-B*44:02 allele,
- the therapeutic composition comprises: (i) a recombinant polypeptide comprising at least two cancer-specific CD8+ T cell epitopes, or (ii) a polynucleotide encoding a recombinant polypeptide comprising at least two cancer-specific CD8+ T cell epitopes, (iii) a vector comprising (i) or (ii), (iv) antigen presenting cells (APCs) comprising (i), (ii), or (iii), or (v) T cells stimulated with APCs comprising (i), (ii), or (iii); wherein the at least two cancer-specific CD8+ T cell epitopes are KPRPDVTNEL and HELGFKVVL.
- APCs antigen presenting cells
- the therapeutic composition comprises: (i) a recombinant polypeptide consisting of at least two cancer-specific CD8+ T cell epitopes, or (ii) a polynucleotide encoding a recombinant polypeptide consisting of at least two cancer-specific CD8+ T cell epitopes, (iii) a vector comprising (i) or (ii), (iv) antigen presenting cells (APCs) comprising (i), (ii), or (iii), or (v) T cells stimulated with APCs comprising (i), (ii), or (iii); wherein the at least two cancerspecific CD8+ T cell epitopes are KPRPDVTNEL and HELGFKVVL.
- APCs antigen presenting cells
- the therapeutic composition comprises: (i) a recombinant polypeptide comprising at least two cancer-specific CD8+ T cell epitopes, or (ii) a polynucleotide encoding a recombinant polypeptide comprising at least two cancer-specific CD8+ T cell epitopes, (iii) a vector comprising (i) or (ii), (iv) antigen presenting cells (APCs) comprising (i), (ii), or (iii), or (v) T cells stimulated with APCs comprising (i), (ii), or (iii); wherein the at least two cancer-specific CD8+ T cell epitopes are KPRPDVTNEL and HELGFKVVL and wherein the composition is for use in treating cancer is a subject that expresses an MHC encoded by an HLA-B*07:02 allele, an HLA-B*35:03 allele, an HLA-C*07:02 allele, an
- the therapeutic composition comprises: (i) a recombinant polypeptide consisting of at least two cancer-specific CD8+ T cell epitopes, or (ii) a polynucleotide encoding a recombinant polypeptide consisting of at least two cancer-specific CD8+ T cell epitopes, (iii) a vector comprising (i) or (ii), (iv) antigen presenting cells (APCs) comprising (i), (ii), or (iii), or (v) T cells stimulated with APCs comprising (i), (ii), or (iii); wherein the at least two cancerspecific CD8+ T cell epitopes are KPRPDVTNEL and HELGFKVVL and wherein the composition is for use in treating cancer is a subject that expresses an MHC encoded by an HLA- B*07:02 allele, an HLA-B*35:03 allele, an HLA-C*07:02 allele,
- the therapeutic composition comprises: (i) a recombinant polypeptide comprising at least two cancer-specific CD8+ T cell epitopes, or (ii) a polynucleotide encoding a recombinant polypeptide comprising at least two cancer-specific CD8+ T cell epitopes, (iii) a vector comprising (i) or (ii), (iv) antigen presenting cells (APCs) comprising (i), (ii), or (iii), or (v) T cells stimulated with APCs comprising (i), (ii), or (iii); wherein the at least two cancer-specific CD8+ T cell epitopes are KEFAFLEHSL and HELGFKVVL.
- the therapeutic composition comprises: (i) a recombinant polypeptide consisting of at least two cancer-specific CD8+ T cell epitopes, or (ii) a polynucleotide encoding a recombinant polypeptide consisting of at least two cancer-specific CD8+ T cell epitopes, (iii) a vector comprising (i) or (ii), (iv) antigen presenting cells (APCs) comprising (i), (ii), or (iii), or (v) T cells stimulated with APCs comprising (i), (ii), or (iii); wherein the at least two cancerspecific CD8+ T cell epitopes are KEFAFLEHSL and HELGFKVVL.
- the therapeutic composition comprises: (i) a recombinant polypeptide comprising at least two cancer-specific CD8+ T cell epitopes, or (ii) a polynucleotide encoding a recombinant polypeptide comprising at least two cancer-specific CD8+ T cell epitopes, (iii) a vector comprising (i) or (ii), (iv) antigen presenting cells (APCs) comprising (i), (ii), or (iii), or (v) T cells stimulated with APCs comprising (i), (ii), or (iii); wherein the at least two cancer-specific CD8+ T cell epitopes are KEFAFLEHSL and HELGFKVVL and wherein the composition is for use in treating cancer is a subject that expresses an MHC encoded by an HLA-B*18:01 allele, an HLA-B*40:01 allele, an HLA-B*44:02 allele, an MHC encoded
- the therapeutic composition comprises: (i) a recombinant polypeptide consisting of at least two cancer-specific CD8+ T cell epitopes, or (ii) a polynucleotide encoding a recombinant polypeptide consisting of at least two cancer-specific CD8+ T cell epitopes, (iii) a vector comprising (i) or (ii), (iv) antigen presenting cells (APCs) comprising (i), (ii), or (iii), or (v) T cells stimulated with APCs comprising (i), (ii), or (iii); wherein the at least two cancer-specific CD8+ T cell epitopes are KEFAFLEHSL and HELGFKVVL and wherein the composition is for use in treating cancer is a subject that expresses an MHC encoded by an HLA-B* 18:01 allele, an HLA-B*40:01 allele, an HLA- B*44:02 allele
- the therapeutic composition comprises: (i) a recombinant polypeptide comprising at least three cancer-specific CD8+ T cell epitopes, or (ii) a polynucleotide encoding a recombinant polypeptide comprising at least three cancer-specific CD8+ T cell epitopes, (iii) a vector comprising (i) or (ii), (iv) antigen presenting cells (APCs) comprising (i), (ii), or (iii), or (v) T cells stimulated with APCs comprising (i), (ii), or (iii); wherein the at least three cancer-specific CD8+ T cell epitopes are GVYDGREHTV and KLVELEHTL and SPSSASLAL.
- the therapeutic composition comprises:
- a polynucleotide encoding a recombinant polypeptide consisting of at least three cancerspecific CD8+ T cell epitopes (iii) a vector comprising (i) or (ii), (iv) antigen presenting cells (APCs) comprising (i), (ii), or (iii), or (v) T cells stimulated with APCs comprising (i), (ii), or
- the therapeutic composition comprises:
- a polynucleotide encoding a recombinant polypeptide comprising at least three cancerspecific CD8+ T cell epitopes (iii) a vector comprising (i) or (ii), (iv) antigen presenting cells (APCs) comprising (i), (ii), or (iii), or (v) T cells stimulated with APCs comprising (i), (ii), or
- composition for use in treating cancer is a subject that expresses an MHC encoded by an HLA-A*02:01 allele, an HLA-B*07:02 allele, an HLA-B*35:03 allele, or any combination thereof.
- the therapeutic composition comprises: (i) a recombinant polypeptide consisting of at least three cancer-specific CD8+ T cell epitopes, or (ii) a polynucleotide encoding a recombinant polypeptide consisting of at least three cancer-specific CD8+ T cell epitopes, (iii) a vector comprising (i) or (ii), (iv) antigen presenting cells (APCs) comprising (i), (ii), or (iii), or (v) T cells stimulated with APCs comprising (i), (ii), or (iii); wherein the at least three cancer-specific CD8+ T cell epitopes are GVYDGREHTV and KLVELEHTL and SPSSASLAL and wherein the composition is for use in treating cancer is a subject that expresses an MHC encoded by an HLA-A*02:01 allele, an HLA- B*07:02 allele, an HLA-B*35
- the therapeutic composition comprises: (i) a recombinant polypeptide comprising at least three cancer-specific CD8+ T cell epitopes, or (ii) a polynucleotide encoding a recombinant polypeptide comprising at least three cancer-specific CD8+ T cell epitopes, (iii) a vector comprising (i) or (ii), (iv) antigen presenting cells (APCs) comprising (i), (ii), or (iii), or (v) T cells stimulated with APCs comprising (i), (ii), or (iii); wherein the at least three cancer-specific CD8+ T cell epitopes are GVYDGREHTV and KLVELEHTL and KPRPDVTNEL.
- the therapeutic composition comprises: (i) a recombinant polypeptide consisting of at least three cancer-specific CD8+ T cell epitopes, or (ii) a polynucleotide encoding a recombinant polypeptide consisting of at least three cancer-specific CD8+ T cell epitopes, (iii) a vector comprising (i) or (ii), (iv) antigen presenting cells (APCs) comprising (i), (ii), or (iii), or (v) T cells stimulated with APCs comprising (i), (ii), or (iii); wherein the at least three cancer-specific CD8+ T cell epitopes are GVYDGREHTV and KLVELEHTL and KPRPDVTNEL.
- the therapeutic composition comprises: (i) a recombinant polypeptide comprising at least three cancer-specific CD8+ T cell epitopes, or (ii) a polynucleotide encoding a recombinant polypeptide comprising at least three cancer-specific CD8+ T cell epitopes, (iii) a vector comprising (i) or (ii), (iv) antigen presenting cells (APCs) comprising (i), (ii), or (iii), or (v) T cells stimulated with APCs comprising (i), (ii), or (iii); wherein the at least three cancer-specific CD8+ T cell epitopes are GVYDGREHTV and KLVELEHTL and KPRPDVTNEL and wherein the composition is for use in treating cancer is a subject that expresses an MHC encoded by an HLA-A*02:01 allele, an HLA-B*07:02 allele, an HLA-B*35
- the therapeutic composition comprises: (i) a recombinant polypeptide consisting of at least three cancer-specific CD8+ T cell epitopes, or (ii) a polynucleotide encoding a recombinant polypeptide consisting of at least three cancer-specific CD8+ T cell epitopes, (iii) a vector comprising (i) or (ii), (iv) antigen presenting cells (APCs) comprising (i), (ii), or (iii), or (v) T cells stimulated with APCs comprising (i), (ii), or (iii); wherein the at least three cancerspecific CD8+ T cell epitopes are GVYDGREHTV and KLVELEHTL and KPRPDVTNEL and wherein the composition is for use in treating cancer is a subject that expresses an MHC encoded by an HLA-A*02:01 allele, an HLA-B*07:02 allele, an HLA-B*
- the therapeutic composition comprises: (i) a recombinant polypeptide comprising at least three cancer-specific CD8+ T cell epitopes, or (ii) a polynucleotide encoding a recombinant polypeptide comprising at least three cancer-specific CD8+ T cell epitopes, (iii) a vector comprising (i) or (ii), (iv) antigen presenting cells (APCs) comprising (i), (ii), or (iii), or (v) T cells stimulated with APCs comprising (i), (ii), or (iii); wherein the at least three cancer-specific CD8+ T cell epitopes are GVYDGREHTV and KLVELEHTL and KEFAFLEHSL.
- the therapeutic composition comprises: (i) a recombinant polypeptide consisting of at least three cancer-specific CD8+ T cell epitopes, or (ii) a polynucleotide encoding a recombinant polypeptide consisting of at least three cancer-specific CD8+ T cell epitopes, (iii) a vector comprising (i) or (ii), (iv) antigen presenting cells (APCs) comprising (i), (ii), or (iii), or (v) T cells stimulated with APCs comprising (i), (ii), or (iii); wherein the at least three cancer-specific CD8+ T cell epitopes are GVYDGREHTV and KLVELEHTL and KEFAFLEHSL.
- the therapeutic composition comprises: (i) a recombinant polypeptide comprising at least three cancer-specific CD8+ T cell epitopes, or (ii) a polynucleotide encoding a recombinant polypeptide comprising at least three cancer-specific CD8+ T cell epitopes, (iii) a vector comprising (i) or (ii), (iv) antigen presenting cells (APCs) comprising (i), (ii), or (iii), or (v) T cells stimulated with APCs comprising (i), (ii), or (iii); wherein the at least three cancer-specific CD8+ T cell epitopes are GVYDGREHTV and KLVELEHTL and KEFAFLEHSL and wherein the composition is for use in treating cancer is a subject that expresses an MHC encoded by an HLA-A*02:01 allele, an HLA-B*40:01 allele, an HLA-B*44
- the therapeutic composition comprises: (i) a recombinant polypeptide consisting of at least three cancer-specific CD8+ T cell epitopes, or (ii) a polynucleotide encoding a recombinant polypeptide consisting of at least three cancer-specific CD8+ T cell epitopes, (iii) a vector comprising (i) or (ii), (iv) antigen presenting cells (APCs) comprising (i), (ii), or (iii), or (v) T cells stimulated with APCs comprising (i), (ii), or (iii); wherein the at least three cancerspecific CD8+ T cell epitopes are GVYDGREHTV and KLVELEHTL and KEFAFLEHSL and wherein the composition is for use in treating cancer is a subject that expresses an MHC encoded by an HLA-A*02:01 allele, an HLA-B*40:01 allele, an HLA-B*
- the therapeutic composition comprises: (i) a recombinant polypeptide comprising at least three cancer-specific CD8+ T cell epitopes, or (ii) a polynucleotide encoding a recombinant polypeptide comprising at least three cancer-specific CD8+ T cell epitopes, (iii) a vector comprising (i) or (ii), (iv) antigen presenting cells (APCs) comprising (i), (ii), or (iii), or (v) T cells stimulated with APCs comprising (i), (ii), or (iii); wherein the at least three cancer-specific CD8+ T cell epitopes are GVYDGREHTV and KLVELEHTL and HELGFKVVL.
- the therapeutic composition comprises: (i) a recombinant polypeptide consisting of at least three cancer-specific CD8+ T cell epitopes, or (ii) a polynucleotide encoding a recombinant polypeptide consisting of at least three cancer-specific CD8+ T cell epitopes, (iii) a vector comprising (i) or (ii), (iv) antigen presenting cells (APCs) comprising (i), (ii), or (iii), or (v) T cells stimulated with APCs comprising (i), (ii), or (iii); wherein the at least three cancer-specific CD8+ T cell epitopes are GVYDGREHTV and KLVELEHTL and HELGFKVVL.
- the therapeutic composition comprises: (i) a recombinant polypeptide comprising at least three cancer-specific CD8+ T cell epitopes, or (ii) a polynucleotide encoding a recombinant polypeptide comprising at least three cancer-specific CD8+ T cell epitopes, (iii) a vector comprising (i) or (ii), (iv) antigen presenting cells (APCs) comprising (i), (ii), or (iii), or (v) T cells stimulated with APCs comprising (i), (ii), or (iii); wherein the at least three cancer-specific CD8+ T cell epitopes are GVYDGREHTV and KLVELEHTL and HELGFKVVL and wherein the composition is for use in treating cancer is a subject that expresses an MHC encoded by an HLA-A*02:01 allele, an HLA-B*18:01 allele, an HLA-B*
- the therapeutic composition comprises: (i) a recombinant polypeptide consisting of at least three cancer-specific CD8+ T cell epitopes, or (ii) a polynucleotide encoding a recombinant polypeptide consisting of at least three cancer-specific CD8+ T cell epitopes, (iii) a vector comprising (i) or (ii), (iv) antigen presenting cells (APCs) comprising (i), (ii), or (iii), or (v) T cells stimulated with APCs comprising (i), (ii), or (iii); wherein the at least three cancer-specific CD8+ T cell epitopes are GVYDGREHTV and KLVELEHTL and HELGFKVVL and wherein the composition is for use in treating cancer is a subject that expresses an MHC encoded by an HLA-A*02:01 allele, an HLA-B*18:01 allele, an HLA-
- the therapeutic composition comprises: (i) a recombinant polypeptide comprising at least three cancer-specific CD8+ T cell epitopes, or (ii) a polynucleotide encoding a recombinant polypeptide comprising at least three cancer-specific CD8+ T cell epitopes, (iii) a vector comprising (i) or (ii), (iv) antigen presenting cells (APCs) comprising (i), (ii), or (iii), or (v) T cells stimulated with APCs comprising (i), (ii), or (iii); wherein the at least three cancer-specific CD8+ T cell epitopes are GVYDGREHTV and SPSSASLAL and KPRPDVTNEL.
- APCs antigen presenting cells
- the therapeutic composition comprises: (i) a recombinant polypeptide consisting of at least three cancer-specific CD8+ T cell epitopes, or (ii) a polynucleotide encoding a recombinant polypeptide consisting of at least three cancer-specific CD8+ T cell epitopes, (iii) a vector comprising (i) or (ii), (iv) antigen presenting cells (APCs) comprising (i), (ii), or (iii), or (v) T cells stimulated with APCs comprising (i), (ii), or (iii); wherein the at least three cancer-specific CD8+ T cell epitopes are GVYDGREHTV and SPSSASLAL and KPRPDVTNEL.
- APCs antigen presenting cells
- the therapeutic composition comprises: (i) a recombinant polypeptide comprising at least three cancer-specific CD8+ T cell epitopes, or (ii) a polynucleotide encoding a recombinant polypeptide comprising at least three cancer-specific CD8+ T cell epitopes, (iii) a vector comprising (i) or (ii), (iv) antigen presenting cells (APCs) comprising (i), (ii), or (iii), or (v) T cells stimulated with APCs comprising (i), (ii), or (iii); wherein the at least three cancer-specific CD8+ T cell epitopes are GVYDGREHTV and SPSSASLAL and KPRPDVTNEL and wherein the composition is for use in treating cancer is a subject that expresses an MHC encoded by an HLA-A*02:01 allele, an HLA-B*07:02 allele, an HLA-B*35:
- the therapeutic composition comprises: (i) a recombinant polypeptide consisting of at least three cancer-specific CD8+ T cell epitopes, or (ii) a polynucleotide encoding a recombinant polypeptide consisting of at least three cancer-specific CD8+ T cell epitopes, (iii) a vector comprising (i) or (ii), (iv) antigen presenting cells (APCs) comprising (i), (ii), or (iii), or (v) T cells stimulated with APCs comprising (i), (ii), or (iii); wherein the at least three cancerspecific CD8+ T cell epitopes are GVYDGREHTV and SPSSASLAL and KPRPDVTNEL and wherein the composition is for use in treating cancer is a subject that expresses an MHC encoded by an HLA-A*02:01 allele, an HLA-B*07:02 allele, an HLA-B*35
- the therapeutic composition comprises: (i) a recombinant polypeptide comprising at least three cancer-specific CD8+ T cell epitopes, or (ii) a polynucleotide encoding a recombinant polypeptide comprising at least three cancer-specific CD8+ T cell epitopes, (iii) a vector comprising (i) or (ii), (iv) antigen presenting cells (APCs) comprising (i), (ii), or (iii), or (v) T cells stimulated with APCs comprising (i), (ii), or (iii); wherein the at least three cancer-specific CD8+ T cell epitopes are GVYDGREHTV and SPSSASLAL and KEFAFLEHSL.
- APCs antigen presenting cells
- the therapeutic composition comprises: (i) a recombinant polypeptide consisting of at least three cancer-specific CD8+ T cell epitopes, or (ii) a polynucleotide encoding a recombinant polypeptide consisting of at least three cancer-specific CD8+ T cell epitopes, (iii) a vector comprising (i) or (ii), (iv) antigen presenting cells (APCs) comprising (i), (ii), or (iii), or (v) T cells stimulated with APCs comprising (i), (ii), or (iii); wherein the at least three cancer- specific CD8+ T cell epitopes are GVYDGREHTV and SPSSASLAL and KEFAFLEHSL.
- APCs antigen presenting cells
- the therapeutic composition comprises: (i) a recombinant polypeptide comprising at least three cancer-specific CD8+ T cell epitopes, or (ii) a polynucleotide encoding a recombinant polypeptide comprising at least three cancer-specific CD8+ T cell epitopes, (iii) a vector comprising (i) or (ii), (iv) antigen presenting cells (APCs) comprising (i), (ii), or (iii), or (v) T cells stimulated with APCs comprising (i), (ii), or (iii); wherein the at least three cancer-specific CD8+ T cell epitopes are GVYDGREHTV and SPSSASLAL and KEFAFLEHSL and wherein the composition is for use in treating cancer is a subject that expresses an MHC encoded by an HLA-A*02:01 allele, an HLA-B*07:02 allele, an HLA-B*35:
- the therapeutic composition comprises: (i) a recombinant polypeptide consisting of at least three cancer-specific CD8+ T cell epitopes, or (ii) a polynucleotide encoding a recombinant polypeptide consisting of at least three cancer-specific CD8+ T cell epitopes, (iii) a vector comprising (i) or (ii), (iv) antigen presenting cells (APCs) comprising (i), (ii), or (iii), or (v) T cells stimulated with APCs comprising (i), (ii), or (iii); wherein the at least three cancer-specific CD8+ T cell epitopes are GVYDGREHTV and SPSSASLAL and KEFAFLEHSL and wherein the composition is for use in treating cancer is a subject that expresses an MHC encoded by an HLA-A*02:01 allele, an HLA-B*07:02 allele, an HLA-B*
- the therapeutic composition comprises: (i) a recombinant polypeptide comprising at least three cancer-specific CD8+ T cell epitopes, or (ii) a polynucleotide encoding a recombinant polypeptide comprising at least three cancer-specific CD8+ T cell epitopes, (iii) a vector comprising (i) or (ii), (iv) antigen presenting cells (APCs) comprising (i), (ii), or (iii), or (v) T cells stimulated with APCs comprising (i), (ii), or (iii); wherein the at least three cancer-specific CD8+ T cell epitopes are GVYDGREHTV and SPSSASLAL and HELGFKVVL.
- the therapeutic composition comprises: (i) a recombinant polypeptide consisting of at least three cancer-specific CD8+ T cell epitopes, or (ii) a polynucleotide encoding a recombinant polypeptide consisting of at least three cancer-specific CD8+ T cell epitopes, (iii) a vector comprising (i) or (ii), (iv) antigen presenting cells (APCs) comprising (i), (ii), or (iii), or (v) T cells stimulated with APCs comprising (i), (ii), or (iii); wherein the at least three cancer-specific CD8+ T cell epitopes are GVYDGREHTV and SPSSASLAL and HELGFKVVL.
- APCs antigen presenting cells
- the therapeutic composition comprises: (i) a recombinant polypeptide comprising at least three cancer-specific CD8+ T cell epitopes, or (ii) a polynucleotide encoding a recombinant polypeptide comprising at least three cancer-specific CD8+ T cell epitopes, (iii) a vector comprising (i) or (ii), (iv) antigen presenting cells (APCs) comprising (i), (ii), or (iii), or (v) T cells stimulated with APCs comprising (i), (ii), or (iii); wherein the at least three cancer-specific CD8+ T cell epitopes are GVYDGREHTV and SPSSASLAL and HELGFKVVL and wherein the composition is for use in treating cancer is a subject that expresses an MHC encoded by an HLA-A*02:01 allele, an HLA-B*07:02 allele, an HLA-B*35
- the therapeutic composition comprises: (i) a recombinant polypeptide consisting of at least three cancer-specific CD8+ T cell epitopes, or (ii) a polynucleotide encoding a recombinant polypeptide consisting of at least three cancer-specific CD8+ T cell epitopes, (iii) a vector comprising (i) or (ii), (iv) antigen presenting cells (APCs) comprising (i), (ii), or (iii), or (v) T cells stimulated with APCs comprising (i), (ii), or (iii); wherein the at least three cancer-specific CD8+ T cell epitopes are GVYDGREHTV and SPSSASLAL and HELGFKVVL and wherein the composition is for use in treating cancer is a subject that expresses an MHC encoded by an HLA-A*02:01 allele, an HLA- B*07:02 allele, an HLA-B
- the therapeutic composition comprises: (i) a recombinant polypeptide comprising at least three cancer-specific CD8+ T cell epitopes, or (ii) a polynucleotide encoding a recombinant polypeptide comprising at least three cancer-specific CD8+ T cell epitopes, (iii) a vector comprising (i) or (ii), (iv) antigen presenting cells (APCs) comprising (i), (ii), or (iii), or (v) T cells stimulated with APCs comprising (i), (ii), or (iii); wherein the at least three cancer-specific CD8+ T cell epitopes are GVYDGREHTV and KPRPDVTNEL and KEFAFLEHSL.
- the therapeutic composition comprises: (i) a recombinant polypeptide consisting of at least three cancer-specific CD8+ T cell epitopes, or (ii) a polynucleotide encoding a recombinant polypeptide consisting of at least three cancer-specific CD8+ T cell epitopes, (iii) a vector comprising (i) or (ii), (iv) antigen presenting cells (APCs) comprising (i), (ii), or (iii), or (v) T cells stimulated with APCs comprising (i), (ii), or (iii); wherein the at least three cancer-specific CD8+ T cell epitopes are GVYDGREHTV and KPRPDVTNEL and KEFAFLEHSL.
- the therapeutic composition comprises: (i) a recombinant polypeptide comprising at least three cancer-specific CD8+ T cell epitopes, or (ii) a polynucleotide encoding a recombinant polypeptide comprising at least three cancer-specific CD8+ T cell epitopes, (iii) a vector comprising (i) or (ii), (iv) antigen presenting cells (APCs) comprising (i), (ii), or (iii), or (v) T cells stimulated with APCs comprising (i), (ii), or (iii); wherein the at least three cancer-specific CD8+ T cell epitopes are GVYDGREHTV and KPRPDVTNEL and KEFAFLEHSL and wherein the composition is for use in treating cancer is a subject that expresses an MHC encoded by an HLA-A*02:01 allele, an HLA-B*07:02 allele, an HLA-B*
- the therapeutic composition comprises: (i) a recombinant polypeptide consisting of at least three cancer-specific CD8+ T cell epitopes, or (ii) a polynucleotide encoding a recombinant polypeptide consisting of at least three cancer-specific CD8+ T cell epitopes, (iii) a vector comprising (i) or (ii), (iv) antigen presenting cells (APCs) comprising (i), (ii), or (iii), or (v) T cells stimulated with APCs comprising (i), (ii), or (iii); wherein the at least three cancer-specific CD8+ T cell epitopes are GVYDGREHTV and KPRPDVTNEL and KEFAFLEHSL and wherein the composition is for use in treating cancer is a subject that expresses an MHC encoded by an HLA-A*02:01 allele, an HLA-B*07:02 allele, an HLA-
- the therapeutic composition comprises: (i) a recombinant polypeptide comprising at least three cancer-specific CD8+ T cell epitopes, or (ii) a polynucleotide encoding a recombinant polypeptide comprising at least three cancer-specific CD8+ T cell epitopes, (iii) a vector comprising (i) or (ii), (iv) antigen presenting cells (APCs) comprising (i), (ii), or (iii), or (v) T cells stimulated with APCs comprising (i), (ii), or (iii); wherein the at least three cancer-specific CD8+ T cell epitopes are GVYDGREHTV and KPRPDVTNEL and HELGFKVVL.
- the therapeutic composition comprises: (i) a recombinant polypeptide consisting of at least three cancer-specific CD8+ T cell epitopes, or (ii) a polynucleotide encoding a recombinant polypeptide consisting of at least three cancer-specific CD8+ T cell epitopes, (iii) a vector comprising (i) or (ii), (iv) antigen presenting cells (APCs) comprising (i), (ii), or (iii), or (v) T cells stimulated with APCs comprising (i), (ii), or (iii); wherein the at least three cancer-specific CD8+ T cell epitopes are GVYDGREHTV and KPRPDVTNEL and HELGFKVVL.
- the therapeutic composition comprises: (i) a recombinant polypeptide comprising at least three cancer-specific CD8+ T cell epitopes, or (ii) a polynucleotide encoding a recombinant polypeptide comprising at least three cancer-specific CD8+ T cell epitopes, (iii) a vector comprising (i) or (ii), (iv) antigen presenting cells (APCs) comprising (i), (ii), or (iii), or (v) T cells stimulated with APCs comprising (i), (ii), or (iii); wherein the at least three cancer-specific CD8+ T cell epitopes are GVYDGREHTV and KPRPDVTNEL and HELGFKVVL and wherein the composition is for use in treating cancer is a subject that expresses an MHC encoded by an HLA-A*02:01 allele, an HLA-B*07:02 allele, an HLA-B
- the therapeutic composition comprises: (i) a recombinant polypeptide consisting of at least three cancer-specific CD8+ T cell epitopes, or (ii) a polynucleotide encoding a recombinant polypeptide consisting of at least three cancer-specific CD8+ T cell epitopes, (iii) a vector comprising (i) or (ii), (iv) antigen presenting cells (APCs) comprising (i), (ii), or (iii), or (v) T cells stimulated with APCs comprising (i), (ii), or (iii); wherein the at least three cancer- specific CD8+ T cell epitopes are GVYDGREHTV and KPRPDVTNEL and HELGFKVVL and wherein the composition is for use in treating cancer is a subject that expresses an MHC encoded by an HLA-A*02:01 allele, an HLA-B*07:02 allele, an HLA
- the therapeutic composition comprises: (i) a recombinant polypeptide comprising at least three cancer-specific CD8+ T cell epitopes, or (ii) a polynucleotide encoding a recombinant polypeptide comprising at least three cancer-specific CD8+ T cell epitopes, (iii) a vector comprising (i) or (ii), (iv) antigen presenting cells (APCs) comprising (i), (ii), or (iii), or (v) T cells stimulated with APCs comprising (i), (ii), or (iii); wherein the at least three cancer-specific CD8+ T cell epitopes are KLVELEHTL and SPSSASLAL and KPRPDVTNEL.
- the therapeutic composition comprises: (i) a recombinant polypeptide consisting of at least three cancer-specific CD8+ T cell epitopes, or (ii) a polynucleotide encoding a recombinant polypeptide consisting of at least three cancer-specific CD8+ T cell epitopes, (iii) a vector comprising (i) or (ii), (iv) antigen presenting cells (APCs) comprising (i), (ii), or (iii), or (v) T cells stimulated with APCs comprising (i), (ii), or (iii); wherein the at least three cancer-specific CD8+ T cell epitopes are KLVELEHTL and SPSSASLAL and KPRPDVTNEL.
- APCs antigen presenting cells
- the therapeutic composition comprises: (i) a recombinant polypeptide comprising at least three cancer-specific CD8+ T cell epitopes, or (ii) a polynucleotide encoding a recombinant polypeptide comprising at least three cancer-specific CD8+ T cell epitopes, (iii) a vector comprising (i) or (ii), (iv) antigen presenting cells (APCs) comprising (i), (ii), or (iii), or (v) T cells stimulated with APCs comprising (i), (ii), or (iii); wherein the at least three cancer-specific CD8+ T cell epitopes are KLVELEHTL and SPSSASLAL and KPRPDVTNEL L and wherein the composition is for use in treating cancer is a subject that expresses an MHC encoded by an HLA-A*02:01 allele, an HLA-B*07:02 allele, an HLA-B*35:03
- the therapeutic composition comprises: (i) a recombinant polypeptide consisting of at least three cancer-specific CD8+ T cell epitopes, or (ii) a polynucleotide encoding a recombinant polypeptide consisting of at least three cancer-specific CD8+ T cell epitopes, (iii) a vector comprising (i) or (ii), (iv) antigen presenting cells (APCs) comprising (i), (ii), or (iii), or (v) T cells stimulated with APCs comprising (i), (ii), or (iii); wherein the at least three cancerspecific CD8+ T cell epitopes are KLVELEHTL and SPSSASLAL and KPRPDVTNEL and wherein the composition is for use in treating cancer is a subject that expresses an MHC encoded by an HLA-A*02:01 allele, an HLA-B*07:02 allele, an HLA-B*35:03
- the therapeutic composition comprises: (i) a recombinant polypeptide comprising at least three cancer-specific CD8+ T cell epitopes, or (ii) a polynucleotide encoding a recombinant polypeptide comprising at least three cancer-specific CD8+ T cell epitopes, (iii) a vector comprising (i) or (ii), (iv) antigen presenting cells (APCs) comprising (i), (ii), or (iii), or (v) T cells stimulated with APCs comprising (i), (ii), or (iii); wherein the at least three cancer-specific CD8+ T cell epitopes are KLVELEHTL and SPSSASLAL and KEFAFLEHSL.
- the therapeutic composition comprises: (i) a recombinant polypeptide consisting of at least three cancer-specific CD8+ T cell epitopes, or (ii) a polynucleotide encoding a recombinant polypeptide consisting of at least three cancer-specific CD8+ T cell epitopes, (iii) a vector comprising (i) or (ii), (iv) antigen presenting cells (APCs) comprising (i), (ii), or (iii), or (v) T cells stimulated with APCs comprising (i), (ii), or (iii); wherein the at least three cancer-specific CD8+ T cell epitopes are KLVELEHTL and SPSSASLAL and KEFAFLEHSL.
- the therapeutic composition comprises: (i) a recombinant polypeptide comprising at least three cancer-specific CD8+ T cell epitopes, or (ii) a polynucleotide encoding a recombinant polypeptide comprising at least three cancer-specific CD8+ T cell epitopes, (iii) a vector comprising (i) or (ii), (iv) antigen presenting cells (APCs) comprising (i), (ii), or (iii), or (v) T cells stimulated with APCs comprising (i), (ii), or (iii); wherein the at least three cancer-specific CD8+ T cell epitopes are KLVELEHTL and SPSSASLAL and KEFAFLEHSL and wherein the composition is for use in treating cancer is a subject that expresses an MHC encoded by an HLA-A*02:01 allele, an HLA-B*07:02 allele, an HLA-B*35:03 all
- the therapeutic composition comprises: (i) a recombinant polypeptide consisting of at least three cancer-specific CD8+ T cell epitopes, or (ii) a polynucleotide encoding a recombinant polypeptide consisting of at least three cancer-specific CD8+ T cell epitopes, (iii) a vector comprising (i) or (ii), (iv) antigen presenting cells (APCs) comprising (i), (ii), or (iii), or (v) T cells stimulated with APCs comprising (i), (ii), or (iii); wherein the at least three cancer-specific CD8+ T cell epitopes are KLVELEHTL and SPSSASLAL and KEFAFLEHSL and wherein the composition is for use in treating cancer is a subject that expresses an MHC encoded by an HLA-A*02:01 allele, an HLA-B*07:02 allele, an HLA-B*35:
- the therapeutic composition comprises: (i) a recombinant polypeptide comprising at least three cancer-specific CD8+ T cell epitopes, or (ii) a polynucleotide encoding a recombinant polypeptide comprising at least three cancer-specific CD8+ T cell epitopes, (iii) a vector comprising (i) or (ii), (iv) antigen presenting cells (APCs) comprising (i), (ii), or (iii), or (v) T cells stimulated with APCs comprising (i), (ii), or (iii); wherein the at least three cancer-specific CD8+ T cell epitopes are KLVELEHTL and SPSSASLAL and HELGFKVVL.
- the therapeutic composition comprises: (i) a recombinant polypeptide consisting of at least three cancer-specific CD8+ T cell epitopes, or (ii) a polynucleotide encoding a recombinant polypeptide consisting of at least three cancer-specific CD8+ T cell epitopes, (iii) a vector comprising (i) or (ii), (iv) antigen presenting cells (APCs) comprising (i), (ii), or (iii), or (v) T cells stimulated with APCs comprising (i), (ii), or (iii); wherein the at least three cancer-specific CD8+ T cell epitopes are KLVELEHTL and SPSSASLAL and HELGFKVVL.
- the therapeutic composition comprises: (i) a recombinant polypeptide comprising at least three cancer-specific CD8+ T cell epitopes, or (ii) a polynucleotide encoding a recombinant polypeptide comprising at least three cancer-specific CD8+ T cell epitopes, (iii) a vector comprising (i) or (ii), (iv) antigen presenting cells (APCs) comprising (i), (ii), or (iii), or (v) T cells stimulated with APCs comprising (i), (ii), or (iii); wherein the at least three cancer-specific CD8+ T cell epitopes are KLVELEHTL and SPSSASLAL and HELGFKVVL and wherein the composition is for use in treating cancer is a subject that expresses an MHC encoded by an HLA-A*02:01 allele, an HLA-B*07:02 allele, an HLA-B*35:03
- the therapeutic composition comprises: (i) a recombinant polypeptide consisting of at least three cancer-specific CD8+ T cell epitopes, or (ii) a polynucleotide encoding a recombinant polypeptide consisting of at least three cancer-specific CD8+ T cell epitopes, (iii) a vector comprising (i) or (ii), (iv) antigen presenting cells (APCs) comprising (i), (ii), or (iii), or (v) T cells stimulated with APCs comprising (i), (ii), or (iii); wherein the at least three cancer-specific CD8+ T cell epitopes are KLVELEHTL and SPSSASLAL and HELGFKVVL and wherein the composition is for use in treating cancer is a subject that expresses an MHC encoded by an HLA-A*02:01 allele, an HLA- B*07:02 allele, an HLA-B*35
- the therapeutic composition comprises: (i) a recombinant polypeptide comprising at least three cancer-specific CD8+ T cell epitopes, or (ii) a polynucleotide encoding a recombinant polypeptide comprising at least three cancer-specific CD8+ T cell epitopes, (iii) a vector comprising (i) or (ii), (iv) antigen presenting cells (APCs) comprising (i), (ii), or (iii), or (v) T cells stimulated with APCs comprising (i), (ii), or (iii); wherein the at least three cancer-specific CD8+ T cell epitopes are KLVELEHTL and KPRPDVTNEL and KEFAFLEHSL.
- the therapeutic composition comprises: (i) a recombinant polypeptide consisting of at least three cancer-specific CD8+ T cell epitopes, or (ii) a polynucleotide encoding a recombinant polypeptide consisting of at least three cancer-specific CD8+ T cell epitopes, (iii) a vector comprising (i) or (ii), (iv) antigen presenting cells (APCs) comprising (i), (ii), or (iii), or (v) T cells stimulated with APCs comprising (i), (ii), or (iii); wherein the at least three cancer-specific CD8+ T cell epitopes are KLVELEHTL and KPRPDVTNEL and KEFAFLEHSL.
- the therapeutic composition comprises: (i) a recombinant polypeptide comprising at least three cancer-specific CD8+ T cell epitopes, or (ii) a polynucleotide encoding a recombinant polypeptide comprising at least three cancer-specific CD8+ T cell epitopes, (iii) a vector comprising (i) or (ii), (iv) antigen presenting cells (APCs) comprising (i), (ii), or (iii), or (v) T cells stimulated with APCs comprising (i), (ii), or (iii); wherein the at least three cancer-specific CD8+ T cell epitopes are KLVELEHTL and KPRPDVTNEL and KEFAFLEHSL and wherein the composition is for use in treating cancer is a subject that expresses an MHC encoded by an HLA-A*02:01 allele, an HLA-B*07:02 allele, an HLA-B*35:
- the therapeutic composition comprises: (i) a recombinant polypeptide consisting of at least three cancer-specific CD8+ T cell epitopes, or (ii) a polynucleotide encoding a recombinant polypeptide consisting of at least three cancer-specific CD8+ T cell epitopes, (iii) a vector comprising (i) or (ii), (iv) antigen presenting cells (APCs) comprising (i), (ii), or (iii), or (v) T cells stimulated with APCs comprising (i), (ii), or (iii); wherein the at least three cancer-specific CD8+ T cell epitopes are KLVELEHTL and KPRPDVTNEL and KEFAFLEHSL and wherein the composition is for use in treating cancer is a subject that expresses an MHC encoded by an HLA-A*02:01 allele, an HLA-B*07:02 allele, an HLA-B*
- the therapeutic composition comprises: (i) a recombinant polypeptide comprising at least three cancer-specific CD8+ T cell epitopes, or (ii) a polynucleotide encoding a recombinant polypeptide comprising at least three cancer-specific CD8+ T cell epitopes, (iii) a vector comprising (i) or (ii), (iv) antigen presenting cells (APCs) comprising (i), (ii), or (iii), or (v) T cells stimulated with APCs comprising (i), (ii), or (iii); wherein the at least three cancer-specific CD8+ T cell epitopes are KLVELEHTL and KPRPDVTNEL and HELGFKVVL.
- the therapeutic composition comprises: (i) a recombinant polypeptide consisting of at least three cancer-specific CD8+ T cell epitopes, or (ii) a polynucleotide encoding a recombinant polypeptide consisting of at least three cancer-specific CD8+ T cell epitopes, (iii) a vector comprising (i) or (ii), (iv) antigen presenting cells (APCs) comprising (i), (ii), or (iii), or (v) T cells stimulated with APCs comprising (i), (ii), or (iii); wherein the at least three cancer-specific CD8+ T cell epitopes are KLVELEHTL and KPRPDVTNEL and HELGFKVVL.
- the therapeutic composition comprises: (i) a recombinant polypeptide comprising at least three cancer-specific CD8+ T cell epitopes, or (ii) a polynucleotide encoding a recombinant polypeptide comprising at least three cancer-specific CD8+ T cell epitopes, (iii) a vector comprising (i) or (ii), (iv) antigen presenting cells (APCs) comprising (i), (ii), or (iii), or (v) T cells stimulated with APCs comprising (i), (ii), or (iii); wherein the at least three cancer-specific CD8+ T cell epitopes are KLVELEHTL and KPRPDVTNEL and HELGFKVVL and wherein the composition is for use in treating cancer is a subject that expresses an MHC encoded by an HLA-A*02:01 allele, an HLA-B*07:02 allele, an HLA-B*35
- the therapeutic composition comprises: (i) a recombinant polypeptide consisting of at least three cancer-specific CD8+ T cell epitopes, or (ii) a polynucleotide encoding a recombinant polypeptide consisting of at least three cancer-specific CD8+ T cell epitopes, (iii) a vector comprising (i) or (ii), (iv) antigen presenting cells (APCs) comprising (i), (ii), or (iii), or (v) T cells stimulated with APCs comprising (i), (ii), or (iii); wherein the at least three cancerspecific CD8+ T cell epitopes are KLVELEHTL and KPRPDVTNEL and HELGFKVVL and wherein the composition is for use in treating cancer is a subject that expresses an MHC encoded by an HLA-A*02:01 allele, an HLA-B*07:02 allele, an HLA-B*
- the therapeutic composition comprises: (i) a recombinant polypeptide comprising at least three cancer-specific CD8+ T cell epitopes, or (ii) a polynucleotide encoding a recombinant polypeptide comprising at least three cancer-specific CD8+ T cell epitopes, (iii) a vector comprising (i) or (ii), (iv) antigen presenting cells (APCs) comprising (i), (ii), or (iii), or (v) T cells stimulated with APCs comprising (i), (ii), or (iii); wherein the at least three cancer-specific CD8+ T cell epitopes are KLVELEHTL and KEFAFLEHSL and HELGFKVVL.
- the therapeutic composition comprises: (i) a recombinant polypeptide consisting of at least three cancer-specific CD8+ T cell epitopes, or (ii) a polynucleotide encoding a recombinant polypeptide consisting of at least three cancer-specific CD8+ T cell epitopes, (iii) a vector comprising (i) or (ii), (iv) antigen presenting cells (APCs) comprising (i), (ii), or (iii), or (v) T cells stimulated with APCs comprising (i), (ii), or (iii); wherein the at least three cancer-specific CD8+ T cell epitopes are KLVELEHTL and KEFAFLEHSL and HELGFKVVL.
- the therapeutic composition comprises: (i) a recombinant polypeptide comprising at least three cancer-specific CD8+ T cell epitopes, or (ii) a polynucleotide encoding a recombinant polypeptide comprising at least three cancer-specific CD8+ T cell epitopes, (iii) a vector comprising (i) or (ii), (iv) antigen presenting cells (APCs) comprising (i), (ii), or (iii), or (v) T cells stimulated with APCs comprising (i), (ii), or (iii); wherein the at least three cancer-specific CD8+ T cell epitopes are KLVELEHTL and KEFAFLEHSL and HELGFKVVL and wherein the composition is for use in treating cancer is a subject that expresses an MHC encoded by an HLA-A*02:01 allele, an HLA-B*18:01 allele, an HLA-B*40
- the therapeutic composition comprises: (i) a recombinant polypeptide consisting of at least three cancer-specific CD8+ T cell epitopes, or (ii) a polynucleotide encoding a recombinant polypeptide consisting of at least three cancer-specific CD8+ T cell epitopes, (iii) a vector comprising (i) or (ii), (iv) antigen presenting cells (APCs) comprising (i), (ii), or (iii), or (v) T cells stimulated with APCs comprising (i), (ii), or (iii); wherein the at least three cancer-specific CD8+ T cell epitopes are KLVELEHTL and KEFAFLEHSL and HELGFKVVL and wherein the composition is for use in treating cancer is a subject that expresses an MHC encoded by an HLA-A*02:01 allele, an HLA-B*18:01 allele, an HLA-B
- the therapeutic composition comprises: (i) a recombinant polypeptide comprising at least three cancer-specific CD8+ T cell epitopes, or (ii) a polynucleotide encoding a recombinant polypeptide comprising at least three cancer-specific CD8+ T cell epitopes, (iii) a vector comprising (i) or (ii), (iv) antigen presenting cells (APCs) comprising (i), (ii), or (iii), or (v) T cells stimulated with APCs comprising (i), (ii), or (iii); wherein the at least three cancer-specific CD8+ T cell epitopes are SPSSASLAL and KPRPDVTNEL and KEFAFLEHSL.
- the therapeutic composition comprises: (i) a recombinant polypeptide consisting of at least three cancer-specific CD8+ T cell epitopes, or (ii) a polynucleotide encoding a recombinant polypeptide consisting of at least three cancer-specific CD8+ T cell epitopes, (iii) a vector comprising (i) or (ii), (iv) antigen presenting cells (APCs) comprising (i), (ii), or (iii), or (v) T cells stimulated with APCs comprising (i), (ii), or (iii); wherein the at least three cancer-specific CD8+ T cell epitopes are SPSSASLAL and KPRPDVTNEL and KEFAFLEHSL.
- APCs antigen presenting cells
- the therapeutic composition comprises: (i) a recombinant polypeptide comprising at least three cancer-specific CD8+ T cell epitopes, or (ii) a polynucleotide encoding a recombinant polypeptide comprising at least three cancer-specific CD8+ T cell epitopes, (iii) a vector comprising (i) or (ii), (iv) antigen presenting cells (APCs) comprising (i), (ii), or (iii), or (v) T cells stimulated with APCs comprising (i), (ii), or (iii); wherein the at least three cancer-specific CD8+ T cell epitopes are SPSSASLAL and KPRPDVTNEL and KEFAFLEHSL and wherein the composition is for use in treating cancer is a subject that expresses an MHC encoded by an HLA-B*07:02 allele, an HLA-B*35:03 allele, an HLA-C*07:02
- the therapeutic composition comprises: (i) a recombinant polypeptide consisting of at least three cancer-specific CD8+ T cell epitopes, or (ii) a polynucleotide encoding a recombinant polypeptide consisting of at least three cancer-specific CD8+ T cell epitopes, (iii) a vector comprising (i) or (ii), (iv) antigen presenting cells (APCs) comprising (i), (ii), or (iii), or (v) T cells stimulated with APCs comprising (i), (ii), or (iii); wherein the at least three cancer-specific CD8+ T cell epitopes are SPSSASLAL and KPRPDVTNEL and KEFAFLEHSL and wherein the composition is for use in treating cancer is a subject that expresses an MHC encoded by an HLA-B*07:02 allele, an HLA-B*35:03 allele, an HLA-C*07
- the therapeutic composition comprises: (i) a recombinant polypeptide comprising at least three cancer-specific CD8+ T cell epitopes, or (ii) a polynucleotide encoding a recombinant polypeptide comprising at least three cancer-specific CD8+ T cell epitopes, (iii) a vector comprising (i) or (ii), (iv) antigen presenting cells (APCs) comprising (i), (ii), or (iii), or (v) T cells stimulated with APCs comprising (i), (ii), or (iii); wherein the at least three cancer-specific CD8+ T cell epitopes are SPSSASLAL and KPRPDVTNEL and HELGFKVVL.
- the therapeutic composition comprises: (i) a recombinant polypeptide consisting of at least three cancer-specific CD8+ T cell epitopes, or (ii) a polynucleotide encoding a recombinant polypeptide consisting of at least three cancer-specific CD8+ T cell epitopes, (iii) a vector comprising (i) or (ii), (iv) antigen presenting cells (APCs) comprising (i), (ii), or (iii), or (v) T cells stimulated with APCs comprising (i), (ii), or (iii); wherein the at least three cancer-specific CD8+ T cell epitopes are SPSSASLAL and KPRPDVTNEL and HELGFKVVL.
- the therapeutic composition comprises: (i) a recombinant polypeptide comprising at least three cancer-specific CD8+ T cell epitopes, or (ii) a polynucleotide encoding a recombinant polypeptide comprising at least three cancer-specific CD8+ T cell epitopes, (iii) a vector comprising (i) or (ii), (iv) antigen presenting cells (APCs) comprising (i), (ii), or (iii), or (v) T cells stimulated with APCs comprising (i), (ii), or (iii); wherein the at least three cancer-specific CD8+ T cell epitopes are SPSSASLAL and KPRPDVTNEL and HELGFKVVL and wherein the composition is for use in treating cancer is a subject that expresses an MHC encoded by an HLA-B*07:02 allele, an HLA-B*35:03 allele, an HLA-C*07:
- the therapeutic composition comprises: (i) a recombinant polypeptide consisting of at least three cancer-specific CD8+ T cell epitopes, or (ii) a polynucleotide encoding a recombinant polypeptide consisting of at least three cancer-specific CD8+ T cell epitopes, (iii) a vector comprising (i) or (ii), (iv) antigen presenting cells (APCs) comprising (i), (ii), or (iii), or (v) T cells stimulated with APCs comprising (i), (ii), or (iii); wherein the at least three cancer-specific CD8+ T cell epitopes are SPSSASLAL and KPRPDVTNEL and HELGFKVVL and wherein the composition is for use in treating cancer is a subject that expresses an MHC encoded by an HLA-B*07:02 allele, an HLA- B*35:03 allele, an HLA-C*
- the therapeutic composition comprises: (i) a recombinant polypeptide comprising at least three cancer-specific CD8+ T cell epitopes, or (ii) a polynucleotide encoding a recombinant polypeptide comprising at least three cancer-specific CD8+ T cell epitopes, (iii) a vector comprising (i) or (ii), (iv) antigen presenting cells (APCs) comprising (i), (ii), or (iii), or (v) T cells stimulated with APCs comprising (i), (ii), or (iii); wherein the at least three cancer-specific CD8+ T cell epitopes are SPSSASLAL and KEFAFLEHSL and HELGFKVVL.
- the therapeutic composition comprises: (i) a recombinant polypeptide consisting of at least three cancer-specific CD8+ T cell epitopes, or (ii) a polynucleotide encoding a recombinant polypeptide consisting of at least three cancer-specific CD8+ T cell epitopes, (iii) a vector comprising (i) or (ii), (iv) antigen presenting cells (APCs) comprising (i), (ii), or (iii), or (v) T cells stimulated with APCs comprising (i), (ii), or (iii); wherein the at least three cancer-specific CD8+ T cell epitopes are SPSSASLAL and KEFAFLEHSL and HELGFKVVL.
- the therapeutic composition comprises: (i) a recombinant polypeptide comprising at least three cancer-specific CD8+ T cell epitopes, or (ii) a polynucleotide encoding a recombinant polypeptide comprising at least three cancer-specific CD8+ T cell epitopes, (iii) a vector comprising (i) or (ii), (iv) antigen presenting cells (APCs) comprising (i), (ii), or (iii), or (v) T cells stimulated with APCs comprising (i), (ii), or (iii); wherein the at least three cancer-specific CD8+ T cell epitopes are SPSSASLAL and KEFAFLEHSL and HELGFKVVL and wherein the composition is for use in treating cancer is a subject that expresses an MHC encoded by an HLA-B*07:02 allele, an HLA-B*35:03 allele, an HLA-B*40:
- the therapeutic composition comprises: (i) a recombinant polypeptide consisting of at least three cancer-specific CD8+ T cell epitopes, or (ii) a polynucleotide encoding a recombinant polypeptide consisting of at least three cancer-specific CD8+ T cell epitopes, (iii) a vector comprising (i) or (ii), (iv) antigen presenting cells (APCs) comprising (i), (ii), or (iii), or (v) T cells stimulated with APCs comprising (i), (ii), or (iii); wherein the at least three cancer-specific CD8+ T cell epitopes are SPSSASLAL and KEFAFLEHSL and HELGFKVVL and wherein the composition is for use in treating cancer is a subject that expresses an MHC encoded by an HLA-B*07:02 allele, an HLA-B*35:03 allele, an HLA-B*
- the therapeutic composition comprises: (i) a recombinant polypeptide comprising at least three cancer-specific CD8+ T cell epitopes, or (ii) a polynucleotide encoding a recombinant polypeptide comprising at least three cancer-specific CD8+ T cell epitopes, (iii) a vector comprising (i) or (ii), (iv) antigen presenting cells (APCs) comprising (i), (ii), or (iii), or (v) T cells stimulated with APCs comprising (i), (ii), or (iii); wherein the at least three cancer-specific CD8+ T cell epitopes are KPRPDVTNEL and KEFAFLEHSL and HELGFKVVL.
- the therapeutic composition comprises: (i) a recombinant polypeptide consisting of at least three cancer-specific CD8+ T cell epitopes, or (ii) a polynucleotide encoding a recombinant polypeptide consisting of at least three cancer-specific CD8+ T cell epitopes, (iii) a vector comprising (i) or (ii), (iv) antigen presenting cells (APCs) comprising (i), (ii), or (iii), or (v) T cells stimulated with APCs comprising (i), (ii), or (iii); wherein the at least three cancer-specific CD8+ T cell epitopes are KPRPDVTNEL and KEFAFLEHSL and HELGFKVVL.
- the therapeutic composition comprises: (i) a recombinant polypeptide comprising at least three cancer-specific CD8+ T cell epitopes, or (ii) a polynucleotide encoding a recombinant polypeptide comprising at least three cancer-specific CD8+ T cell epitopes, (iii) a vector comprising (i) or (ii), (iv) antigen presenting cells (APCs) comprising (i), (ii), or (iii), or (v) T cells stimulated with APCs comprising (i), (ii), or (iii); wherein the at least three cancer-specific CD8+ T cell epitopes are KPRPDVTNEL and KEFAFLEHSL and HELGFKVVL and wherein the composition is for use in treating cancer is a subject that expresses an MHC encoded by an HLA-B*07:02 allele, an HLA-B*35:03 allele, an HLA-C*
- the therapeutic composition comprises: (i) a recombinant polypeptide consisting of at least three cancer-specific CD8+ T cell epitopes, or (ii) a polynucleotide encoding a recombinant polypeptide consisting of at least three cancer-specific CD8+ T cell epitopes, (iii) a vector comprising (i) or (ii), (iv) antigen presenting cells (APCs) comprising (i), (ii), or (iii), or (v) T cells stimulated with APCs comprising (i), (ii), or (iii); wherein the at least three cancer-specific CD8+ T cell epitopes are KPRPDVTNEL and KEFAFLEHSL and HELGFKVVL and wherein the composition is for use in treating cancer is a subject that expresses an MHC encoded by an HLA-B*07:02 allele, an HLA-B*35:03 allele, an HLA-
- the therapeutic composition comprises: (i) a recombinant polypeptide comprising at least four cancer-specific CD8+ T cell epitopes, or (ii) a polynucleotide encoding a recombinant polypeptide comprising at least four cancer-specific CD8+ T cell epitopes, (iii) a vector comprising (i) or (ii), (iv) antigen presenting cells (APCs) comprising (i), (ii), or (iii), or (v) T cells stimulated with APCs comprising (i), (ii), or (iii); wherein the at least four cancer-specific CD8+ T cell epitopes are GVYDGREHTV and KLVELEHTL and SPSSASLAL and KPRPDVTNEL.
- the therapeutic composition comprises: (i) a recombinant polypeptide consisting of at least four cancer-specific CD8+ T cell epitopes, or (ii) a polynucleotide encoding a recombinant polypeptide consisting of at least four cancer-specific CD8+ T cell epitopes, (iii) a vector comprising (i) or (ii), (iv) antigen presenting cells (APCs) comprising (i), (ii), or (iii), or (v) T cells stimulated with APCs comprising (i), (ii), or (iii); wherein the at least four cancer-specific CD8+ T cell epitopes are GVYDGREHTV and KLVELEHTL and SPSSASLAL and KPRPDVTNEL.
- the therapeutic composition comprises: (i) a recombinant polypeptide comprising at least four cancer-specific CD8+ T cell epitopes, or (ii) a polynucleotide encoding a recombinant polypeptide comprising at least four cancer-specific CD8+ T cell epitopes, (iii) a vector comprising (i) or (ii), (iv) antigen presenting cells (APCs) comprising (i), (ii), or (iii), or (v) T cells stimulated with APCs comprising (i), (ii), or (iii); wherein the at least four cancerspecific CD8+ T cell epitopes are GVYDGREHTV and KLVELEHTL and SPSSASLAL and KPRPDVTNEL and wherein the composition is for use in treating cancer is a subject that expresses an MHC encoded by an HLA-A*02:01 allele, an HLA-B*07:02 allele, an HLA
- the therapeutic composition comprises: (i) a recombinant polypeptide consisting of at least four cancer-specific CD8+ T cell epitopes, or (ii) a polynucleotide encoding a recombinant polypeptide consisting of at four cancer-specific CD8+ T cell epitopes, (iii) a vector comprising (i) or (ii), (iv) antigen presenting cells (APCs) comprising (i), (ii), or (iii), or (v) T cells stimulated with APCs comprising (i), (ii), or (iii); wherein the at least four cancer-specific CD8+ T cell epitopes are GVYDGREHTV and KLVELEHTL and SPSSASLAL and KPRPDVTNEL and wherein the composition is for use in treating cancer is a subject that expresses an MHC encoded by an HLA-A*02:01 allele, an HLA-B*07:02 allele, an
- the therapeutic composition comprises: (i) a recombinant polypeptide comprising at least four cancer-specific CD8+ T cell epitopes, or (ii) a polynucleotide encoding a recombinant polypeptide comprising at least four cancer-specific CD8+ T cell epitopes, (iii) a vector comprising (i) or (ii), (iv) antigen presenting cells (APCs) comprising (i), (ii), or (iii), or (v) T cells stimulated with APCs comprising (i), (ii), or (iii); wherein the at least four cancer-specific CD8+ T cell epitopes are GVYDGREHTV and KLVELEHTL and SPSSASLAL and KEFAFLEHSL.
- the therapeutic composition comprises: (i) a recombinant polypeptide consisting of at least four cancer-specific CD8+ T cell epitopes, or (ii) a polynucleotide encoding a recombinant polypeptide consisting of at least four cancer-specific CD8+ T cell epitopes, (iii) a vector comprising (i) or (ii), (iv) antigen presenting cells (APCs) comprising (i), (ii), or (iii), or (v) T cells stimulated with APCs comprising (i), (ii), or (iii); wherein the at least four cancer-specific CD8+ T cell epitopes are GVYDGREHTV and KLVELEHTL and SPSSASLAL and KEFAFLEHSL.
- the therapeutic composition comprises: (i) a recombinant polypeptide comprising at least four cancer-specific CD8+ T cell epitopes, or (ii) a polynucleotide encoding a recombinant polypeptide comprising at least four cancer-specific CD8+ T cell epitopes, (iii) a vector comprising (i) or (ii), (iv) antigen presenting cells (APCs) comprising (i), (ii), or (iii), or (v) T cells stimulated with APCs comprising (i), (ii), or (iii); wherein the at least four cancerspecific CD8+ T cell epitopes are GVYDGREHTV and KLVELEHTL and SPSSASLAL and KEFAFLEHSL and wherein the composition is for use in treating cancer is a subject that expresses an MHC encoded by an HLA-A*02:01 allele, an HLA-B*07:02 allele, an HLA
- the therapeutic composition comprises: (i) a recombinant polypeptide consisting of at least four cancer-specific CD8+ T cell epitopes, or (ii) a polynucleotide encoding a recombinant polypeptide consisting of at four cancer-specific CD8+ T cell epitopes, (iii) a vector comprising (i) or (ii), (iv) antigen presenting cells (APCs) comprising (i), (ii), or (iii), or (v) T cells stimulated with APCs comprising (i), (ii), or (iii); wherein the at least four cancer-specific CD8+ T cell epitopes are GVYDGREHTV and KLVELEHTL and SPSSASLAL and KEFAFLEHSL and wherein the composition is for use in treating cancer is a subject that expresses an MHC encoded by an HLA-A*02:01 allele, an HLA-B*07:02 allele, an
- the therapeutic composition comprises: (i) a recombinant polypeptide comprising at least four cancer-specific CD8+ T cell epitopes, or (ii) a polynucleotide encoding a recombinant polypeptide comprising at least four cancer-specific CD8+ T cell epitopes, (iii) a vector comprising (i) or (ii), (iv) antigen presenting cells (APCs) comprising (i), (ii), or (iii), or (v) T cells stimulated with APCs comprising (i), (ii), or (iii); wherein the at least four cancer-specific CD8+ T cell epitopes are GVYDGREHTV and KLVELEHTL and SPSSASLAL and HELGFKWL.
- the therapeutic composition comprises: (i) a recombinant polypeptide consisting of at least four cancer-specific CD8+ T cell epitopes, or (ii) a polynucleotide encoding a recombinant polypeptide consisting of at least four cancer-specific CD8+ T cell epitopes, (iii) a vector comprising (i) or (ii), (iv) antigen presenting cells (APCs) comprising (i), (ii), or (iii), or (v) T cells stimulated with APCs comprising (i), (ii), or (iii); wherein the at least four cancer-specific CD8+ T cell epitopes are GVYDGREHTV and KLVELEHTL and SPSSASLAL and HELGFKVVL.
- the therapeutic composition comprises: (i) a recombinant polypeptide comprising at least four cancer-specific CD8+ T cell epitopes, or (ii) a polynucleotide encoding a recombinant polypeptide comprising at least four cancer-specific CD8+ T cell epitopes, (iii) a vector comprising (i) or (ii), (iv) antigen presenting cells (APCs) comprising (i), (ii), or (iii), or (v) T cells stimulated with APCs comprising (i), (ii), or (iii); wherein the at least four cancerspecific CD8+ T cell epitopes are GVYDGREHTV and KLVELEHTL and SPSSASLAL and HELGFKVVL and wherein the composition is for use in treating cancer is a subject that expresses an MHC encoded by an HLA-A*02:01 allele, an HLA-B*07:02 allele, an H
- the therapeutic composition comprises: (i) a recombinant polypeptide consisting of at least four cancer-specific CD8+ T cell epitopes, or (ii) a polynucleotide encoding a recombinant polypeptide consisting of at four cancer-specific CD8+ T cell epitopes, (iii) a vector comprising (i) or (ii), (iv) antigen presenting cells (APCs) comprising (i), (ii), or (iii), or (v) T cells stimulated with APCs comprising (i), (ii), or (iii); wherein the at least four cancer-specific CD8+ T cell epitopes are GVYDGREHTV and KLVELEHTL and SPSSASLAL and HELGFKVVL and wherein the composition is for use in treating cancer is a subject that expresses an MHC encoded by an HLA- A*02:01 allele, an HLA-B*07:02 allele,
- the therapeutic composition comprises: (i) a recombinant polypeptide comprising at least four cancer-specific CD8+ T cell epitopes, or (ii) a polynucleotide encoding a recombinant polypeptide comprising at least four cancer-specific CD8+ T cell epitopes, (iii) a vector comprising (i) or (ii), (iv) antigen presenting cells (APCs) comprising (i), (ii), or (iii), or (v) T cells stimulated with APCs comprising (i), (ii), or (iii); wherein the at least four cancer-specific CD8+ T cell epitopes are GVYDGREHTV and SPSSASLAL and KPRPDVTNEL and KEFAFLEHSL.
- the therapeutic composition comprises: (i) a recombinant polypeptide consisting of at least four cancer-specific CD8+ T cell epitopes, or (ii) a polynucleotide encoding a recombinant polypeptide consisting of at least four cancer-specific CD8+ T cell epitopes, (iii) a vector comprising (i) or (ii), (iv) antigen presenting cells (APCs) comprising (i), (ii), or (iii), or (v) T cells stimulated with APCs comprising (i), (ii), or (iii); wherein the at least four cancer-specific CD8+ T cell epitopes are GVYDGREHTV and SPSSASLAL and KPRPDVTNEL and KEFAFLEHSL.
- the therapeutic composition comprises: (i) a recombinant polypeptide comprising at least four cancer-specific CD8+ T cell epitopes, or (ii) a polynucleotide encoding a recombinant polypeptide comprising at least four cancer-specific CD8+ T cell epitopes, (iii) a vector comprising (i) or (ii), (iv) antigen presenting cells (APCs) comprising (i), (ii), or (iii), or (v) T cells stimulated with APCs comprising (i), (ii), or (iii); wherein the at least four cancerspecific CD8+ T cell epitopes are GVYDGREHTV and SPSSASLAL and KPRPDVTNEL and KEFAFLEHSL and wherein the composition is for use in treating cancer is a subject that expresses an MHC encoded by an HLA-A*02:01 allele, an HLA-B*07:02 allele, an H
- the therapeutic composition comprises: (i) a recombinant polypeptide consisting of at least four cancer-specific CD8+ T cell epitopes, or (ii) a polynucleotide encoding a recombinant polypeptide consisting of at four cancer-specific CD8+ T cell epitopes, (iii) a vector comprising (i) or (ii), (iv) antigen presenting cells (APCs) comprising (i), (ii), or (iii), or (v) T cells stimulated with APCs comprising (i), (ii), or (iii); wherein the at least four cancer-specific CD8+ T cell epitopes are GVYDGREHTV and SPSSASLAL and KPRPDVTNEL and KEFAFLEHSL and wherein the composition is for use in treating cancer is a subject that expresses an MHC encoded by an HLA- A*02:01 allele, an HLA-B*07:02 allele,
- the therapeutic composition comprises: (i) a recombinant polypeptide comprising at least four cancer-specific CD8+ T cell epitopes, or (ii) a polynucleotide encoding a recombinant polypeptide comprising at least four cancer-specific CD8+ T cell epitopes, (iii) a vector comprising (i) or (ii), (iv) antigen presenting cells (APCs) comprising (i), (ii), or (iii), or (v) T cells stimulated with APCs comprising (i), (ii), or (iii); wherein the at least four cancer-specific CD8+ T cell epitopes are GVYDGREHTV and SPSSASLAL and KPRPDVTNEL and HELGFKVVL.
- the therapeutic composition comprises: (i) a recombinant polypeptide consisting of at least four cancer-specific CD8+ T cell epitopes, or (ii) a polynucleotide encoding a recombinant polypeptide consisting of at least four cancer-specific CD8+ T cell epitopes, (iii) a vector comprising (i) or (ii), (iv) antigen presenting cells (APCs) comprising (i), (ii), or (iii), or (v) T cells stimulated with APCs comprising (i), (ii), or (iii); wherein the at least four cancer-specific CD8+ T cell epitopes are GVYDGREHTV and SPSSASLAL and KPRPDVTNEL and HELGFKVVL.
- the therapeutic composition comprises: (i) a recombinant polypeptide comprising at least four cancer-specific CD8+ T cell epitopes, or (ii) a polynucleotide encoding a recombinant polypeptide comprising at least four cancer-specific CD8+ T cell epitopes, (iii) a vector comprising (i) or (ii), (iv) antigen presenting cells (APCs) comprising (i), (ii), or (iii), or (v) T cells stimulated with APCs comprising (i), (ii), or (iii); wherein the at least four cancerspecific CD8+ T cell epitopes are GVYDGREHTV and SPSSASLAL and KPRPDVTNEL and HELGFKVVL and wherein the composition is for use in treating cancer is a subject that expresses an MHC encoded by an HLA-A*02:01 allele, an HLA-B*07:02 allele, an
- the therapeutic composition comprises: (i) a recombinant polypeptide consisting of at least four cancer-specific CD8+ T cell epitopes, or (ii) a polynucleotide encoding a recombinant polypeptide consisting of at four cancer-specific CD8+ T cell epitopes, (iii) a vector comprising (i) or (ii), (iv) antigen presenting cells (APCs) comprising (i), (ii), or (iii), or (v) T cells stimulated with APCs comprising (i), (ii), or (iii); wherein the at least four cancer-specific CD8+ T cell epitopes are GVYDGREHTV and SPSSASLAL and KPRPDVTNEL and HELGFKVVL and wherein the composition is for use in treating cancer is a subject that expresses an MHC encoded by an HLA-A*02:01 allele, an HLA-B*07:02 allele
- the therapeutic composition comprises: (i) a recombinant polypeptide comprising at least four cancer-specific CD8+ T cell epitopes, or (ii) a polynucleotide encoding a recombinant polypeptide comprising at least four cancer-specific CD8+ T cell epitopes, (iii) a vector comprising (i) or (ii), (iv) antigen presenting cells (APCs) comprising (i), (ii), or (iii), or (v) T cells stimulated with APCs comprising (i), (ii), or (iii); wherein the at least four cancer-specific CD8+ T cell epitopes are GVYDGREHTV and KPRPDVTNEL and KEFAFLEHSL and HELGFKVVL.
- the therapeutic composition comprises: (i) a recombinant polypeptide consisting of at least four cancer-specific CD8+ T cell epitopes, or (ii) a polynucleotide encoding a recombinant polypeptide consisting of at least four cancer-specific CD8+ T cell epitopes, (iii) a vector comprising (i) or (ii), (iv) antigen presenting cells (APCs) comprising (i), (ii), or (iii), or (v) T cells stimulated with APCs comprising (i), (ii), or (iii); wherein the at least four cancer-specific CD8+ T cell epitopes are GVYDGREHTV and KPRPDVTNEL and KEFAFLEHSL and HELGFKVVL.
- the therapeutic composition comprises: (i) a recombinant polypeptide comprising at least four cancer-specific CD8+ T cell epitopes, or (ii) a polynucleotide encoding a recombinant polypeptide comprising at least four cancer-specific CD8+ T cell epitopes, (iii) a vector comprising (i) or (ii), (iv) antigen presenting cells (APCs) comprising (i), (ii), or (iii), or (v) T cells stimulated with APCs comprising (i), (ii), or (iii); wherein the at least four cancerspecific CD8+ T cell epitopes are GVYDGREHTV and KPRPDVTNEL and KEFAFLEHSL and HELGFKVVL and wherein the composition is for use in treating cancer is a subject that expresses an MHC encoded by an HLA-A*02:01 allele, an HLA-B*07:02 allele
- the therapeutic composition comprises: (i) a recombinant polypeptide consisting of at least four cancer-specific CD8+ T cell epitopes, or (ii) a polynucleotide encoding a recombinant polypeptide consisting of at four cancer-specific CD8+ T cell epitopes, (iii) a vector comprising (i) or (ii), (iv) antigen presenting cells (APCs) comprising (i), (ii), or (iii), or (v) T cells stimulated with APCs comprising (i), (ii), or (iii); wherein the at least four cancer-specific CD8+ T cell epitopes are GVYDGREHTV and KPRPDVTNEL and KEFAFLEHSL and HELGFKVVL and wherein the composition is for use in treating cancer is a subject that expresses an MHC encoded by an HLA-A*02:01 allele, an HLA-B*07:02
- the therapeutic composition comprises: (i) a recombinant polypeptide comprising at least four cancer-specific CD8+ T cell epitopes, or (ii) a polynucleotide encoding a recombinant polypeptide comprising at least four cancer-specific CD8+ T cell epitopes, (iii) a vector comprising (i) or (ii), (iv) antigen presenting cells (APCs) comprising (i), (ii), or (iii), or (v) T cells stimulated with APCs comprising (i), (ii), or (iii); wherein the at least four cancer-specific CD8+ T cell epitopes are KLVELEHTL and SPSSASLAL and KPRPDVTNEL and KEFAFLEHSL.
- the therapeutic composition comprises: (i) a recombinant polypeptide consisting of at least four cancer-specific CD8+ T cell epitopes, or (ii) a polynucleotide encoding a recombinant polypeptide consisting of at least four cancer-specific CD8+ T cell epitopes, (iii) a vector comprising (i) or (ii), (iv) antigen presenting cells (APCs) comprising (i), (ii), or (iii), or (v) T cells stimulated with APCs comprising (i), (ii), or (iii); wherein the at least four cancer-specific CD8+ T cell epitopes are KLVELEHTL and SPSSASLAL and KPRPDVTNEL and KEFAFLEHSL.
- the therapeutic composition comprises: (i) a recombinant polypeptide comprising at least four cancer-specific CD8+ T cell epitopes, or (ii) a polynucleotide encoding a recombinant polypeptide comprising at least four cancer-specific CD8+ T cell epitopes, (iii) a vector comprising (i) or (ii), (iv) antigen presenting cells (APCs) comprising (i), (ii), or (iii), or (v) T cells stimulated with APCs comprising (i), (ii), or (iii); wherein the at least four cancerspecific CD8+ T cell epitopes are KLVELEHTL and SPSSASLAL and KPRPDVTNEL and KEFAFLEHSL and wherein the composition is for use in treating cancer is a subject that expresses an MHC encoded by an HLA-A*02:01 allele, an HLA-B*07:02 allele, an HLA-
- the therapeutic composition comprises: (i) a recombinant polypeptide consisting of at least four cancer-specific CD8+ T cell epitopes, or (ii) a polynucleotide encoding a recombinant polypeptide consisting of at four cancer-specific CD8+ T cell epitopes, (iii) a vector comprising (i) or (ii), (iv) antigen presenting cells (APCs) comprising (i), (ii), or (iii), or (v) T cells stimulated with APCs comprising (i), (ii), or (iii); wherein the at least four cancer-specific CD8+ T cell epitopes are KLVELEHTL and SPSSASLAL and KPRPDVTNEL and KEFAFLEHSL and wherein the composition is for use in treating cancer is a subject that expresses an MHC encoded by an HLA- A*02:01 allele, an HLA-B*07:02 allele, an H
- the therapeutic composition comprises: (i) a recombinant polypeptide comprising at least four cancer-specific CD8+ T cell epitopes, or (ii) a polynucleotide encoding a recombinant polypeptide comprising at least four cancer-specific CD8+ T cell epitopes, (iii) a vector comprising (i) or (ii), (iv) antigen presenting cells (APCs) comprising (i), (ii), or (iii), or (v) T cells stimulated with APCs comprising (i), (ii), or (iii); wherein the at least four cancer-specific CD8+ T cell epitopes are KLVELEHTL and SPSSASLAL and KPRPDVTNEL and HELGFKVVL.
- the therapeutic composition comprises: (i) a recombinant polypeptide consisting of at least four cancer-specific CD8+ T cell epitopes, or (ii) a polynucleotide encoding a recombinant polypeptide consisting of at least four cancer-specific CD8+ T cell epitopes, (iii) a vector comprising (i) or (ii), (iv) antigen presenting cells (APCs) comprising (i), (ii), or (iii), or (v) T cells stimulated with APCs comprising (i), (ii), or (iii); wherein the at least four cancer-specific CD8+ T cell epitopes are KLVELEHTL and SPSSASLAL and KPRPDVTNEL and HELGFKVVL.
- the therapeutic composition comprises: (i) a recombinant polypeptide comprising at least four cancer-specific CD8+ T cell epitopes, or (ii) a polynucleotide encoding a recombinant polypeptide comprising at least four cancer-specific CD8+ T cell epitopes, (iii) a vector comprising (i) or (ii), (iv) antigen presenting cells (APCs) comprising (i), (ii), or (iii), or (v) T cells stimulated with APCs comprising (i), (ii), or (iii); wherein the at least four cancerspecific CD8+ T cell epitopes are KLVELEHTL and SPSSASLAL and KPRPDVTNEL and HELGFKVVL and wherein the composition is for use in treating cancer is a subject that expresses an MHC encoded by an HLA-A*02:01 allele, an HLA-B*07:02 allele, an HLA
- the therapeutic composition comprises: (i) a recombinant polypeptide consisting of at least four cancer-specific CD8+ T cell epitopes, or (ii) a polynucleotide encoding a recombinant polypeptide consisting of at four cancer-specific CD8+ T cell epitopes, (iii) a vector comprising (i) or (ii), (iv) antigen presenting cells (APCs) comprising (i), (ii), or (iii), or (v) T cells stimulated with APCs comprising (i), (ii), or (iii); wherein the at least four cancer-specific CD8+ T cell epitopes are KLVELEHTL and SPSSASLAL and KPRPDVTNEL and HELGFKVVL and wherein the composition is for use in treating cancer is a subject that expresses an MHC encoded by an HLA-A*02:01 allele, an HLA-B*07:02 allele, an
- the therapeutic composition comprises: (i) a recombinant polypeptide comprising at least four cancer-specific CD8+ T cell epitopes, or (ii) a polynucleotide encoding a recombinant polypeptide comprising at least four cancer-specific CD8+ T cell epitopes, (iii) a vector comprising (i) or (ii), (iv) antigen presenting cells (APCs) comprising (i), (ii), or (iii), or (v) T cells stimulated with APCs comprising (i), (ii), or (iii); wherein the at least four cancer-specific CD8+ T cell epitopes are KLVELEHTL and KPRPDVTNEL and KEFAFLEHSL and HELGFKVVL.
- the therapeutic composition comprises: (i) a recombinant polypeptide consisting of at least four cancer-specific CD8+ T cell epitopes, or (ii) a polynucleotide encoding a recombinant polypeptide consisting of at least four cancer-specific CD8+ T cell epitopes, (iii) a vector comprising (i) or (ii), (iv) antigen presenting cells (APCs) comprising (i), (ii), or (iii), or (v) T cells stimulated with APCs comprising (i), (ii), or (iii); wherein the at least four cancer- specific CD8+ T cell epitopes are KLVELEHTL and KPRPDVTNEL and KEFAFLEHSL and HELGFKVVL.
- the therapeutic composition comprises: (i) a recombinant polypeptide comprising at least four cancer-specific CD8+ T cell epitopes, or (ii) a polynucleotide encoding a recombinant polypeptide comprising at least four cancer-specific CD8+ T cell epitopes, (iii) a vector comprising (i) or (ii), (iv) antigen presenting cells (APCs) comprising (i), (ii), or (iii), or (v) T cells stimulated with APCs comprising (i), (ii), or (iii); wherein the at least four cancerspecific CD8+ T cell epitopes are KLVELEHTL and KPRPDVTNEL and KEFAFLEHSL and HELGFKVVL and wherein the composition is for use in treating cancer is a subject that expresses an MHC encoded by an HLA-A*02:01 allele, an HLA-B*07:02 allele, an
- the therapeutic composition comprises: (i) a recombinant polypeptide consisting of at least four cancer-specific CD8+ T cell epitopes, or (ii) a polynucleotide encoding a recombinant polypeptide consisting of at four cancer-specific CD8+ T cell epitopes, (iii) a vector comprising (i) or (ii), (iv) antigen presenting cells (APCs) comprising (i), (ii), or (iii), or (v) T cells stimulated with APCs comprising (i), (ii), or (iii); wherein the at least four cancer-specific CD8+ T cell epitopes are KLVELEHTL and KPRPDVTNEL and KEFAFLEHSL and HELGFKVVL and wherein the composition is for use in treating cancer is a subject that expresses an MHC encoded by an HLA-A*02:01 allele, an HLA-B*07:02 allele
- the therapeutic composition comprises: (i) a recombinant polypeptide comprising at least four cancer-specific CD8+ T cell epitopes, or (ii) a polynucleotide encoding a recombinant polypeptide comprising at least four cancer-specific CD8+ T cell epitopes, (iii) a vector comprising (i) or (ii), (iv) antigen presenting cells (APCs) comprising (i), (ii), or (iii), or (v) T cells stimulated with APCs comprising (i), (ii), or (iii); wherein the at least four cancer-specific CD8+ T cell epitopes are SPSSASLAL and KPRPDVTNEL and KEFAFLEHSL and HELGFKVVL.
- the therapeutic composition comprises: (i) a recombinant polypeptide consisting of at least four cancer-specific CD8+ T cell epitopes, or (ii) a polynucleotide encoding a recombinant polypeptide consisting of at least four cancer-specific CD8+ T cell epitopes, (iii) a vector comprising (i) or (ii), (iv) antigen presenting cells (APCs) comprising (i), (ii), or (iii), or (v) T cells stimulated with APCs comprising (i), (ii), or (iii); wherein the at least four cancer-specific CD8+ T cell epitopes are SPSSASLAL and KPRPDVTNEL and KEFAFLEHSL and HELGFKVVL.
- the therapeutic composition comprises: (i) a recombinant polypeptide comprising at least four cancer-specific CD8+ T cell epitopes, or (ii) a polynucleotide encoding a recombinant polypeptide comprising at least four cancer-specific CD8+ T cell epitopes, (iii) a vector comprising (i) or (ii), (iv) antigen presenting cells (APCs) comprising (i), (ii), or (iii), or (v) T cells stimulated with APCs comprising (i), (ii), or (iii); wherein the at least four cancerspecific CD8+ T cell epitopes are SPSSASLAL and KPRPDVTNEL and KEFAFLEHSL and HELGFKVVL and wherein the composition is for use in treating cancer is a subject that expresses an MHC encoded by an HLA-B*07:02 allele, an HLA-B*35:03 allele, an H
- the therapeutic composition comprises: (i) a recombinant polypeptide consisting of at least four cancer-specific CD8+ T cell epitopes, or (ii) a polynucleotide encoding a recombinant polypeptide consisting of at four cancer-specific CD8+ T cell epitopes, (iii) a vector comprising (i) or (ii), (iv) antigen presenting cells (APCs) comprising (i), (ii), or (iii), or (v) T cells stimulated with APCs comprising (i), (ii), or (iii); wherein the at least four cancer-specific CD8+ T cell epitopes are SPSSASLAL and KPRPDVTNEL and KEFAFLEHSL and HELGFKVVL and wherein the composition is for use in treating cancer is a subject that expresses an MHC encoded by an HLA- B*07:02 allele, an HLA-B*35:03 allele,
- the therapeutic composition comprises: (i) a recombinant polypeptide comprising at least five cancer-specific CD8+ T cell epitopes, or (ii) a polynucleotide encoding a recombinant polypeptide comprising at least five cancer-specific CD8+ T cell epitopes, (iii) a vector comprising (i) or (ii), (iv) antigen presenting cells (APCs) comprising (i), (ii), or (iii), or (v) T cells stimulated with APCs comprising (i), (ii), or (iii); wherein the at least five cancer-specific CD8+ T cell epitopes are GVYDGREHTV and KLVELEHTL and SPSSASLAL and KPRPDVTNEL and KEFAFLEHSL.
- the therapeutic composition comprises: (i) a recombinant polypeptide consisting of at least five cancer-specific CD8+ T cell epitopes, or (ii) a polynucleotide encoding a recombinant polypeptide consisting of at least five cancer-specific CD8+ T cell epitopes, (iii) a vector comprising (i) or (ii), (iv) antigen presenting cells (APCs) comprising (i), (ii), or (iii), or (v) T cells stimulated with APCs comprising (i), (ii), or (iii); wherein the at least five cancerspecific CD8+ T cell epitopes are GVYDGREHTV and KLVELEHTL and SPSSASLAL and KPRPDVTNEL and KEFAFLEHSL.
- the therapeutic composition comprises: (i) a recombinant polypeptide comprising at least five cancer-specific CD8+ T cell epitopes, or (ii) a polynucleotide encoding a recombinant polypeptide comprising at least five cancer-specific CD8+ T cell epitopes, (iii) a vector comprising (i) or (ii), (iv) antigen presenting cells (APCs) comprising (i), (ii), or (iii), or (v) T cells stimulated with APCs comprising (i), (ii), or (iii); wherein the at least five cancer-specific CD8+ T cell epitopes are GVYDGREHTV and KLVELEHTL and SPSSASLAL and KPRPDVTNEL and KEFAFLEHSL and wherein the composition is for use in treating cancer is a subject that expresses an MHC encoded by an HLA- A*02:01 allele, an HLA-B*07
- the therapeutic composition comprises: (i) a recombinant polypeptide consisting of at least five cancer-specific CD8+ T cell epitopes, or (ii) a polynucleotide encoding a recombinant polypeptide consisting of at five cancer-specific CD8+ T cell epitopes, (iii) a vector comprising (i) or (ii), (iv) antigen presenting cells (APCs) comprising (i), (ii), or (iii), or (v) T cells stimulated with APCs comprising (i), (ii), or (iii); wherein the at least five cancer-specific CD8+ T cell epitopes are GVYDGREHTV and KLVELEHTL and SPSSASLAL and KPRPDVTNEL and KEFAFLEHSL and wherein the composition is for use in treating cancer is a subject that expresses an MHC encoded by an HLA-A*02:01 allele, an HLA- B*
- the therapeutic composition comprises: (i) a recombinant polypeptide comprising at least five cancer-specific CD8+ T cell epitopes, or (ii) a polynucleotide encoding a recombinant polypeptide comprising at least five cancer-specific CD8+ T cell epitopes, (iii) a vector comprising (i) or (ii), (iv) antigen presenting cells (APCs) comprising (i), (ii), or (iii), or (v) T cells stimulated with APCs comprising (i), (ii), or (iii); wherein the at least five cancer-specific CD8+ T cell epitopes are GVYDGREHTV and KLVELEHTL and SPSSASLAL and KPRPDVTNEL and HELGFKVVL.
- the therapeutic composition comprises: (i) a recombinant polypeptide consisting of at least five cancer-specific CD8+ T cell epitopes, or (ii) a polynucleotide encoding a recombinant polypeptide consisting of at least five cancer-specific CD8+ T cell epitopes, (iii) a vector comprising (i) or (ii), (iv) antigen presenting cells (APCs) comprising (i), (ii), or (iii), or (v) T cells stimulated with APCs comprising (i), (ii), or (iii); wherein the at least five cancerspecific CD8+ T cell epitopes are GVYDGREHTV and KLVELEHTL and SPSSASLAL and KPRPDVTNEL and HELGFKVVL.
- the therapeutic composition comprises: (i) a recombinant polypeptide comprising at least five cancer-specific CD8+ T cell epitopes, or (ii) a polynucleotide encoding a recombinant polypeptide comprising at least five cancer-specific CD8+ T cell epitopes, (iii) a vector comprising (i) or (ii), (iv) antigen presenting cells (APCs) comprising (i), (ii), or (iii), or (v) T cells stimulated with APCs comprising (i), (ii), or (iii); wherein the at least five cancer-specific CD8+ T cell epitopes are GVYDGREHTV and KLVELEHTL and SPSSASLAL and KPRPDVTNEL and HELGFKVVL and wherein the composition is for use in treating cancer is a subject that expresses an MHC encoded by an HLA- A*02:01 allele, an HLA-B*
- the therapeutic composition comprises: (i) a recombinant polypeptide consisting of at least five cancer-specific CD8+ T cell epitopes, or (ii) a polynucleotide encoding a recombinant polypeptide consisting of at five cancer-specific CD8+ T cell epitopes, (iii) a vector comprising (i) or (ii), (iv) antigen presenting cells (APCs) comprising (i), (ii), or (iii), or (v) T cells stimulated with APCs comprising (i), (ii), or (iii); wherein the at least five cancer-specific CD8+ T cell epitopes are GVYDGREHTV and KLVELEHTL and SPSSASLAL and KPRPDVTNEL and HELGFKVVL and wherein the composition is for use in treating cancer is a subject that expresses an MHC encoded by an HLA-A*02:01 allele, an HLA- B
- the therapeutic composition comprises: (i) a recombinant polypeptide comprising at least five cancer-specific CD8+ T cell epitopes, or (ii) a polynucleotide encoding a recombinant polypeptide comprising at least five cancer-specific CD8+ T cell epitopes, (iii) a vector comprising (i) or (ii), (iv) antigen presenting cells (APCs) comprising (i), (ii), or (iii), or (v) T cells stimulated with APCs comprising (i), (ii), or (iii); wherein the at least five cancer-specific CD8+ T cell epitopes are GVYDGREHTV and SPSSASLAL and KPRPDVTNEL and KEFAFLEHSL and HELGFKVVL.
- the therapeutic composition comprises: (i) a recombinant polypeptide consisting of at least five cancer-specific CD8+ T cell epitopes, or (ii) a polynucleotide encoding a recombinant polypeptide consisting of at least five cancer-specific CD8+ T cell epitopes, (iii) a vector comprising (i) or (ii), (iv) antigen presenting cells (APCs) comprising (i), (ii), or (iii), or (v) T cells stimulated with APCs comprising (i), (ii), or (iii); wherein the at least five cancerspecific CD8+ T cell epitopes are GVYDGREHTV and SPSSASLAL and KPRPDVTNEL and KEFAFLEHSL and HELGFKVVL.
- the therapeutic composition comprises: (i) a recombinant polypeptide comprising at least five cancer-specific CD8+ T cell epitopes, or (ii) a polynucleotide encoding a recombinant polypeptide comprising at least five cancer-specific CD8+ T cell epitopes, (iii) a vector comprising (i) or (ii), (iv) antigen presenting cells (APCs) comprising (i), (ii), or (iii), or (v) T cells stimulated with APCs comprising (i), (ii), or (iii); wherein the at least five cancer-specific CD8+ T cell epitopes are GVYDGREHTV and SPSSASLAL and KPRPDVTNEL and KEFAFLEHSL and HELGFKVVL and wherein the composition is for use in treating cancer is a subject that expresses an MHC encoded by an HLA- A*02:01 allele, an HLA-B
- the therapeutic composition comprises: (i) a recombinant polypeptide consisting of at least five cancer-specific CD8+ T cell epitopes, or (ii) a polynucleotide encoding a recombinant polypeptide consisting of at five cancer-specific CD8+ T cell epitopes, (iii) a vector comprising (i) or (ii), (iv) antigen presenting cells (APCs) comprising (i), (ii), or (iii), or (v) T cells stimulated with APCs comprising (i), (ii), or (iii); wherein the at least five cancer-specific CD8+ T cell epitopes are GVYDGREHTV and SPSSASLAL and KPRPDVTNEL and KEFAFLEHSL and HELGFKVVL and wherein the composition is for use in treating cancer is a subject that expresses an HLA-A*02:01 allele, an HLA-B*07:02 all
- the therapeutic composition comprises: (i) a recombinant polypeptide comprising at least five cancer-specific CD8+ T cell epitopes, or (ii) a polynucleotide encoding a recombinant polypeptide comprising at least five cancer-specific CD8+ T cell epitopes, (iii) a vector comprising (i) or (ii), (iv) antigen presenting cells (APCs) comprising (i), (ii), or (iii), or (v) T cells stimulated with APCs comprising (i), (ii), or (iii); wherein the at least five cancer-specific CD8+ T cell epitopes are KLVELEHTL and SPSSASLAL and KPRPDVTNEL and KEFAFLEHSL and HELGFKVVL.
- the therapeutic composition comprises: (i) a recombinant polypeptide consisting of at least five cancer-specific CD8+ T cell epitopes, or (ii) a polynucleotide encoding a recombinant polypeptide consisting of at least five cancer-specific CD8+ T cell epitopes, (iii) a vector comprising (i) or (ii), (iv) antigen presenting cells (APCs) comprising (i), (ii), or (iii), or (v) T cells stimulated with APCs comprising (i), (ii), or (iii); wherein the at least five cancerspecific CD8+ T cell epitopes are KLVELEHTL and SPSSASLAL and KPRPDVTNEL and KEFAFLEHSL and HELGFKVVL.
- the therapeutic composition comprises: (i) a recombinant polypeptide comprising at least five cancer-specific CD8+ T cell epitopes, or (ii) a polynucleotide encoding a recombinant polypeptide comprising at least five cancer-specific CD8+ T cell epitopes, (iii) a vector comprising (i) or (ii), (iv) antigen presenting cells (APCs) comprising (i), (ii), or (iii), or (v) T cells stimulated with APCs comprising (i), (ii), or (iii); wherein the at least five cancer-specific CD8+ T cell epitopes are KLVELEHTL and SPSSASLAL and KPRPDVTNEL and KEFAFLEHSL and HELGFKVVL and wherein the composition is for use in treating cancer is a subject that expresses an MHC encoded by an HLA- A*02:01 allele, an HLA-B*07
- the therapeutic composition comprises: (i) a recombinant polypeptide consisting of at least five cancer-specific CD8+ T cell epitopes, or (ii) a polynucleotide encoding a recombinant polypeptide consisting of at five cancer-specific CD8+ T cell epitopes, (iii) a vector comprising (i) or (ii), (iv) antigen presenting cells (APCs) comprising (i), (ii), or (iii), or (v) T cells stimulated with APCs comprising (i), (ii), or (iii); wherein the at least five cancer-specific CD8+ T cell epitopes are KLVELEHTL and SPSSASLAL and KPRPDVTNEL and KEFAFLEHSL and HELGFKVVL and wherein the composition is for use in treating cancer is a subject that expresses an MHC encoded by an HLA-A*02:01 allele, an HLA-B*
- the therapeutic composition comprises: (i) a recombinant polypeptide comprising at least five cancer-specific CD8+ T cell epitopes, or (ii) a polynucleotide encoding a recombinant polypeptide comprising at least five cancer-specific CD8+ T cell epitopes, (iii) a vector comprising (i) or (ii), (iv) antigen presenting cells (APCs) comprising (i), (ii), or (iii), or (v) T cells stimulated with APCs comprising (i), (ii), or (iii); wherein the at least five cancer-specific CD8+ T cell epitopes are GVYDGREHTV and KLVELEHTL and KPRPDVTNEL and KEFAFLEHSL and HELGFKVVL.
- the therapeutic composition comprises: (i) a recombinant polypeptide consisting of at least five cancer-specific CD8+ T cell epitopes, or (ii) a polynucleotide encoding a recombinant polypeptide consisting of at least five cancer-specific CD8+ T cell epitopes, (iii) a vector comprising (i) or (ii), (iv) antigen presenting cells (APCs) comprising (i), (ii), or (iii), or (v) T cells stimulated with APCs comprising (i), (ii), or (iii); wherein the at least five cancerspecific CD8+ T cell epitopes are GVYDGREHTV and KLVELEHTL and KPRPDVTNEL and KEFAFLEHSL and HELGFKVVL.
- the therapeutic composition comprises: (i) a recombinant polypeptide comprising at least five cancer-specific CD8+ T cell epitopes, or (ii) a polynucleotide encoding a recombinant polypeptide comprising at least five cancer-specific CD8+ T cell epitopes, (iii) a vector comprising (i) or (ii), (iv) antigen presenting cells (APCs) comprising (i), (ii), or (iii), or (v) T cells stimulated with APCs comprising (i), (ii), or (iii); wherein the at least five cancer-specific CD8+ T cell epitopes are GVYDGREHTV and KLVELEHTL and KPRPDVTNEL and KEFAFLEHSL and HELGFKVVL and wherein the composition is for use in treating cancer is a subject that expresses an MHC encoded by an HLA- A*02:01 allele, an HLA-
- the therapeutic composition comprises: (i) a recombinant polypeptide consisting of at least five cancer-specific CD8+ T cell epitopes, or (ii) a polynucleotide encoding a recombinant polypeptide consisting of at five cancer-specific CD8+ T cell epitopes, (iii) a vector comprising (i) or (ii), (iv) antigen presenting cells (APCs) comprising (i), (ii), or (iii), or (v) T cells stimulated with APCs comprising (i), (ii), or (iii); wherein the at least five cancer-specific CD8+ T cell epitopes are GVYDGREHTV and KLVELEHTL and KPRPDVTNEL and KEFAFLEHSL and HELGFKVVL and wherein the composition is for use in treating cancer is a subject that expresses an MHC encoded by an HLA-A*02:01 allele, an HLA
- the therapeutic composition comprises: (i) a recombinant polypeptide comprising at least five cancer-specific CD8+ T cell epitopes, or (ii) a polynucleotide encoding a recombinant polypeptide comprising at least five cancer-specific CD8+ T cell epitopes, (iii) a vector comprising (i) or (ii), (iv) antigen presenting cells (APCs) comprising (i), (ii), or (iii), or (v) T cells stimulated with APCs comprising (i), (ii), or (iii); wherein the at least five cancer-specific CD8+ T cell epitopes are GVYDGREHTV and KLVELEHTL and SPSSASLAL and KEFAFLEHSL and HELGFKVVL.
- the therapeutic composition comprises: (i) a recombinant polypeptide consisting of at least five cancer-specific CD8+ T cell epitopes, or (ii) a polynucleotide encoding a recombinant polypeptide consisting of at least five cancer-specific CD8+ T cell epitopes, (iii) a vector comprising (i) or (ii), (iv) antigen presenting cells (APCs) comprising (i), (ii), or (iii), or (v) T cells stimulated with APCs comprising (i), (ii), or (iii); wherein the at least five cancerspecific CD8+ T cell epitopes are GVYDGREHTV and KLVELEHTL and SPSSASLAL and KEFAFLEHSL and HELGFKVVL.
- the therapeutic composition comprises: (i) a recombinant polypeptide comprising at least five cancer-specific CD8+ T cell epitopes, or (ii) a polynucleotide encoding a recombinant polypeptide comprising at least five cancer-specific CD8+ T cell epitopes, (iii) a vector comprising (i) or (ii), (iv) antigen presenting cells (APCs) comprising (i), (ii), or (iii), or (v) T cells stimulated with APCs comprising (i), (ii), or (iii); wherein the at least five cancer-specific CD8+ T cell epitopes are GVYDGREHTV and KLVELEHTL and SPSSASLAL and KEFAFLEHSL and HELGFKVVL and wherein the composition is for use in treating cancer is a subject that expresses an MHC encoded by an HLA- A*02:01 allele, an HLA-B*
- the therapeutic composition comprises: (i) a recombinant polypeptide consisting of at least five cancer-specific CD8+ T cell epitopes, or (ii) a polynucleotide encoding a recombinant polypeptide consisting of at five cancer-specific CD8+ T cell epitopes, (iii) a vector comprising (i) or (ii), (iv) antigen presenting cells (APCs) comprising (i), (ii), or (iii), or (v) T cells stimulated with APCs comprising (i), (ii), or (iii); wherein the at least five cancer-specific CD8+ T cell epitopes are GVYDGREHTV and KLVELEHTL and SPSSASLAL and KEFAFLEHSL and HELGFKVVL and wherein the composition is for use in treating cancer is a subject that expresses an MHC encoded by an HLA-A*02:01 allele, an HLA- B
- the therapeutic composition comprises: (i) a recombinant polypeptide comprising at least six cancer-specific CD8+ T cell epitopes, or (ii) a polynucleotide encoding a recombinant polypeptide comprising at least six cancer-specific CD8+ T cell epitopes, (iii) a vector comprising (i) or (ii), (iv) antigen presenting cells (APCs) comprising (i), (ii), or (iii), or (v) T cells stimulated with APCs comprising (i), (ii), or (iii); wherein the at least six cancer-specific CD8+ T cell epitopes are GVYDGREHTV and KLVELEHTL and SPSSASLAL and KPRPDVTNEL and KEFAFLEHSL and HELGFKVVL.
- the therapeutic composition comprises: (i) a recombinant polypeptide consisting of at least six cancer-specific CD8+ T cell epitopes, or (ii) a polynucleotide encoding a recombinant polypeptide consisting of at least six cancer-specific CD8+ T cell epitopes, (iii) a vector comprising (i) or (ii), (iv) antigen presenting cells (APCs) comprising (i), (ii), or (iii), or (v) T cells stimulated with APCs comprising (i), (ii), or (iii); wherein the at least six cancer-specific CD8+ T cell epitopes are GVYDGREHTV and KLVELEHTL and SPSSASLAL and KPRPDVTNEL and KEFAFLEHSL and HELGFKVVL.
- the therapeutic composition comprises: (i) a recombinant polypeptide comprising at least six cancer-specific CD8+ T cell epitopes, or (ii) a polynucleotide encoding a recombinant polypeptide comprising at least six cancer-specific CD8+ T cell epitopes, (iii) a vector comprising (i) or (ii), (iv) antigen presenting cells (APCs) comprising (i), (ii), or (iii), or (v) T cells stimulated with APCs comprising (i), (ii), or (iii); wherein the at least six cancer-specific CD8+ T cell epitopes are GVYDGREHTV and KLVELEHTL and SPSSASLAL and KPRPDVTNEL and KEFAFLEHSL and HELGFKVVL and wherein the composition is for use in treating cancer is a subject that expresses an HLA-A*02:01 allele, an HLA-B
- the therapeutic composition comprises: (i) a recombinant polypeptide consisting of at least six cancer-specific CD8+ T cell epitopes, or (ii) a polynucleotide encoding a recombinant polypeptide consisting of at six cancer-specific CD8+ T cell epitopes, (iii) a vector comprising (i) or (ii), (iv) antigen presenting cells (APCs) comprising (i), (ii), or (iii), or (v) T cells stimulated with APCs comprising (i), (ii), or (iii); wherein the at least six cancer-specific CD8+ T cell epitopes are GVYDGREHTV and KLVELEHTL and SPSSASLAL and KPRPDVTNEL and KEFAFLEHSL and HELGFKVVL and wherein the composition is for use in treating cancer is a subject that expresses an MHC encoded by an HLA-A*02:01 all
- the therapeutic composition comprises: (i) a recombinant polypeptide comprising one, two, three, four, five, six, or more cancer-specific CD8+ T cell epitopes, or (ii) a polynucleotide encoding a recombinant polypeptide comprising one, two, three, four, five, six, or more cancer-specific CD8+ T cell epitopes, (iii) a vector comprising (i) or (ii), (iv) antigen presenting cells (APCs) comprising (i), (ii), or (iii), or (v) T cells stimulated with APCs comprising (i), (ii), or (iii); wherein the one, two, three, four, five, six, or more cancerspecific CD8+ T cell epitopes comprise a cancer-specific CD8+ T cell epitope or plurality of cancer-specific CD8+ T cell epitopes described herein and wherein the composition is for use
- the therapeutic composition comprises more than one vectors, e.g., at least 2, at least 3, at least 4, at least 5, or at least 6 vectors, wherein the first, second, third, fourth, fifth, and/or the sixth vector is a vector described herein.
- the first vector comprises (i) a recombinant polypeptide comprising a single epitope, e.g., a single T cell epitope, e.g., a single cancer-specific CD8+ epitope, e.g., a single cancer-specific CD8+ epitope comprising an amino acid sequence as set forth in any of SEQ ID NOs: 1-35, or (ii) a polynucleotide encoding a recombinant polypeptide comprising a single epitope, e.g., a single T cell epitope, e.g., a single cancer-specific CD8+ epitope, e.g., a single cancer-specific CD8+ epitope comprising an amino acid sequence as set forth in any of SEQ ID NOs: 1-35 and the second vector comprises (i) a recombinant polypeptide comprising a single epitope, e.g., a single T cell epitope, e.g.
- the first vector comprises (i) a recombinant polypeptide comprising a single epitope, e.g., a single T cell epitope, e.g., a single cancer-specific CD8+ epitope, e.g., a single cancer-specific CD8+ epitope comprising an amino acid sequence as set forth in any of SEQ ID NOs: 1-35, or (ii) a polynucleotide encoding a recombinant polypeptide comprising a single epitope, e.g., a single T cell epitope, e.g., a single cancer-specific CD8+ epitope, e.g., a single cancer-specific CD8+ epitope comprising an amino acid sequence as set forth in any of SEQ ID NOs: 1-35
- the second vector comprises (i) a recombinant polypeptide comprising a single epitope, e.g., a single T cell epitope, e.g
- the first vector comprises (i) a recombinant polypeptide comprising a single epitope, e.g., a single T cell epitope, e.g., a single cancer-specific CD8+ epitope, e.g., a single cancer-specific CD8+ epitope comprising an amino acid sequence as set forth in any of SEQ ID NOs: 1-35, or (ii) a polynucleotide encoding a recombinant polypeptide comprising a single epitope, e.g., a single T cell epitope, e.g., a single cancer-specific CD8+ epitope, e.g., a single cancer-specific CD8+ epitope comprising an amino acid sequence as set forth in any of SEQ ID NOs: 1-35
- the second vector comprises (i) a recombinant polypeptide comprising a single epitope, e.g., a single T cell epitope, e.g
- the first vector comprises (i) a recombinant polypeptide comprising a single epitope, e.g., a single T cell epitope, e.g., a single cancer-specific CD8+ epitope, e.g., a single cancer-specific CD8+ epitope comprising an amino acid sequence as set forth in any of SEQ ID NOs: 1-35, or (ii) a polynucleotide encoding a recombinant polypeptide comprising a single epitope, e.g., a single T cell epitope, e.g., a single cancer-specific CD8+ epitope, e.g., a single cancer-specific CD8+ epitope comprising an amino acid sequence as set forth in any of SEQ ID NOs: 1-35
- the second vector comprises (i) a recombinant polypeptide comprising a single epitope, e.g., a single T cell epitope, e.g
- the first vector comprises (i) a recombinant polypeptide comprising a single epitope, e.g., a single T cell epitope, e.g., a single cancer-specific CD8+ epitope, e.g., a single cancer-specific CD8+ epitope comprising an amino acid sequence as set forth in any of SEQ ID NOs: 1-35, or (ii) a polynucleotide encoding a recombinant polypeptide comprising a single epitope, e.g., a single T cell epitope, e.g., a single cancer-specific CD8+ epitope, e.g., a single cancer-specific CD8+ epitope comprising an amino acid sequence as set forth in any of SEQ ID NOs: 1-35
- the second vector comprises (i) a recombinant polypeptide comprising a single epitope, e.g., a single T cell epitope, e.g
- the first vector comprises (i) a recombinant polypeptide comprising a single epitope, e.g., a single T cell epitope, e.g., a single cancer-specific CD8+ epitope, e.g., a single cancer-specific CD8+ epitope comprising an amino acid sequence as set forth in any of SEQ ID NOs: 1-6, or (ii) a polynucleotide encoding a recombinant polypeptide comprising a single epitope, e.g., a single T cell epitope, e.g., a single cancer-specific CD8+ epitope, e.g., a single cancer-specific CD8+ epitope comprising an amino acid sequence as set forth in any of SEQ ID NOs: 1-6
- the second vector comprises (i) a recombinant polypeptide comprising a single epitope, e.g., a single T cell epitope, e.g
- the first vector comprises (i) a recombinant polypeptide comprising a single epitope, e.g., a single T cell epitope, e.g., a single cancer-specific CD8+ epitope, e.g., a single cancer-specific CD8+ epitope comprising an amino acid sequence as set forth in any of SEQ ID NOs: 1-6, or (ii) a polynucleotide encoding a recombinant polypeptide comprising a single epitope, e.g., a single T cell epitope, e.g., a single cancer-specific CD8+ epitope, e.g., a single cancer-specific CD8+ epitope comprising an amino acid sequence as set forth in any of SEQ ID NOs: 1-6
- the second vector comprises (i) a recombinant polypeptide comprising a single epitope, e.g., a single T cell epitope, e.g
- the first vector comprises (i) a recombinant polypeptide comprising a single epitope, e.g., a single T cell epitope, e.g., a single cancer-specific CD8+ epitope, e.g., a single cancer-specific CD8+ epitope comprising an amino acid sequence as set forth in any of SEQ ID NOs: 1-6, or (ii) a polynucleotide encoding a recombinant polypeptide comprising a single epitope, e.g., a single T cell epitope, e.g., a single cancer-specific CD8+ epitope, e.g., a single cancer-specific CD8+ epitope comprising an amino acid sequence as set forth in any of SEQ ID NOs: 1-6
- the second vector comprises (i) a recombinant polypeptide comprising a single epitope, e.g., a single T cell epitope, e.g
- the first vector comprises (i) a recombinant polypeptide comprising a single epitope, e.g., a single T cell epitope, e.g., a single cancer-specific CD8+ epitope, e.g., a single cancer-specific CD8+ epitope comprising an amino acid sequence as set forth in any of SEQ ID NOs: 1-6, or (ii) a polynucleotide encoding a recombinant polypeptide comprising a single epitope, e.g., a single T cell epitope, e.g., a single cancer-specific CD8+ epitope, e.g., a single cancer-specific CD8+ epitope comprising an amino acid sequence as set forth in any of SEQ ID NOs: 1-6
- the second vector comprises (i) a recombinant polypeptide comprising a single epitope, e.g., a single T cell epitope, e.g
- the first vector comprises (i) a recombinant polypeptide comprising a single epitope, e.g., a single T cell epitope, e.g., a single cancer-specific CD8+ epitope, e.g., a single cancer-specific CD8+ epitope comprising an amino acid sequence as set forth in any of SEQ ID NOs: 1-6, or (ii) a polynucleotide encoding a recombinant polypeptide comprising a single epitope, e.g., a single T cell epitope, e.g., a single cancer-specific CD8+ epitope, e.g., a single cancer-specific CD8+ epitope comprising an amino acid sequence as set forth in any of SEQ ID NOs: 1-6
- the second vector comprises (i) a recombinant polypeptide comprising a single epitope, e.g., a single T cell epitope, e.g
- the first vector comprises (i) a recombinant polypeptide comprising a single epitope, e.g., a single T cell epitope, e.g., a single cancer-specific CD8+ epitope, e.g., a single cancer-specific CD8+ epitope comprising an amino acid sequence as set forth in any of SEQ ID NOs: 7-12, or (ii) a polynucleotide encoding a recombinant polypeptide comprising a single epitope, e.g., a single T cell epitope, e.g., a single cancer-specific CD8+ epitope, e.g., a single cancer-specific CD8+ epitope comprising an amino acid sequence as set forth in any of SEQ ID NOs: 7-12
- the second vector comprises (i) a recombinant polypeptide comprising a single epitope, e.g., a single T cell epitope, e.g
- the first vector comprises (i) a recombinant polypeptide comprising a single epitope, e.g., a single T cell epitope, e.g., a single cancer-specific CD8+ epitope, e.g., a single cancer-specific CD8+ epitope comprising an amino acid sequence as set forth in any of SEQ ID NOs: 7-12, or (ii) a polynucleotide encoding a recombinant polypeptide comprising a single epitope, e.g., a single T cell epitope, e.g., a single cancer-specific CD8+ epitope, e.g., a single cancer-specific CD8+ epitope comprising an amino acid sequence as set forth in any of SEQ ID NOs: 7-12
- the second vector comprises (i) a recombinant polypeptide comprising a single epitope, e.g., a single T cell epitope, e.g
- the first vector comprises (i) a recombinant polypeptide comprising a single epitope, e.g., a single T cell epitope, e.g., a single cancer-specific CD8+ epitope, e.g., a single cancer-specific CD8+ epitope comprising an amino acid sequence as set forth in any of SEQ ID NOs: 7-12, or (ii) a polynucleotide encoding a recombinant polypeptide comprising a single epitope, e.g., a single T cell epitope, e.g., a single cancer-specific CD8+ epitope, e.g., a single cancer-specific CD8+ epitope comprising an amino acid sequence as set forth in any of SEQ ID NOs: 7-12
- the second vector comprises (i) a recombinant polypeptide comprising a single epitope, e.g., a single T cell epitope, e.g
- the first vector comprises (i) a recombinant polypeptide comprising a single epitope, e.g., a single T cell epitope, e.g., a single cancer-specific CD8+ epitope, e.g., a single cancer-specific CD8+ epitope comprising an amino acid sequence as set forth in any of SEQ ID NOs: 7-12, or (ii) a polynucleotide encoding a recombinant polypeptide comprising a single epitope, e.g., a single T cell epitope, e.g., a single cancer-specific CD8+ epitope, e.g., a single cancer-specific CD8+ epitope comprising an amino acid sequence as set forth in any of SEQ ID NOs: 7-12
- the second vector comprises (i) a recombinant polypeptide comprising a single epitope, e.g., a single T cell epitope, e.g
- the first vector comprises (i) a recombinant polypeptide comprising a single epitope, e.g., a single T cell epitope, e.g., a single cancer-specific CD8+ epitope, e.g., a single cancer-specific CD8+ epitope comprising an amino acid sequence as set forth in any of SEQ ID NOs: 7-12, or (ii) a polynucleotide encoding a recombinant polypeptide comprising a single epitope, e.g., a single T cell epitope, e.g., a single cancer-specific CD8+ epitope, e.g., a single cancer-specific CD8+ epitope comprising an amino acid sequence as set forth in any of SEQ ID NOs: 7-12
- the second vector comprises (i) a recombinant polypeptide comprising a single epitope, e.g., a single T cell epitope, e.g
- the first vector comprises (i) a recombinant polypeptide comprising a single epitope, e.g., a single T cell epitope, e.g., a single cancer-specific CD8+ epitope, e.g., a single cancer-specific CD8+ epitope comprising an amino acid sequence as set forth in any of SEQ ID NOs: 13-18, or (ii) a polynucleotide encoding a recombinant polypeptide comprising a single epitope, e.g., a single T cell epitope, e.g., a single cancer-specific CD8+ epitope, e.g., a single cancer-specific CD8+ epitope comprising an amino acid sequence as set forth in any of SEQ ID NOs: 13-18
- the second vector comprises (i) a recombinant polypeptide comprising a single epitope, e.g., a single T cell epitope, e.g
- the first vector comprises (i) a recombinant polypeptide comprising a single epitope, e.g., a single T cell epitope, e.g., a single cancer-specific CD8+ epitope, e.g., a single cancer-specific CD8+ epitope comprising an amino acid sequence as set forth in any of SEQ ID NOs: 13-18, or (ii) a polynucleotide encoding a recombinant polypeptide comprising a single epitope, e.g., a single T cell epitope, e.g., a single cancer-specific CD8+ epitope, e.g., a single cancer-specific CD8+ epitope comprising an amino acid sequence as set forth in any of SEQ ID NOs: 13-18
- the second vector comprises (i) a recombinant polypeptide comprising a single epitope, e.g., a single T cell epitope, e.g
- the first vector comprises (i) a recombinant polypeptide comprising a single epitope, e.g., a single T cell epitope, e.g., a single cancer-specific CD8+ epitope, e.g., a single cancer-specific CD8+ epitope comprising an amino acid sequence as set forth in any of SEQ ID NOs: 13-18, or (ii) a polynucleotide encoding a recombinant polypeptide comprising a single epitope, e.g., a single T cell epitope, e.g., a single cancer-specific CD8+ epitope, e.g., a single cancer-specific CD8+ epitope comprising an amino acid sequence as set forth in any of SEQ ID NOs: 13-18
- the second vector comprises (i) a recombinant polypeptide comprising a single epitope, e.g., a single T cell epitope, e.g
- the first vector comprises (i) a recombinant polypeptide comprising a single epitope, e.g., a single T cell epitope, e.g., a single cancer-specific CD8+ epitope, e.g., a single cancer-specific CD8+ epitope comprising an amino acid sequence as set forth in any of SEQ ID NOs: 13-18, or (ii) a polynucleotide encoding a recombinant polypeptide comprising a single epitope, e.g., a single T cell epitope, e.g., a single cancer-specific CD8+ epitope, e.g., a single cancer-specific CD8+ epitope comprising an amino acid sequence as set forth in any of SEQ ID NOs: 13-18
- the second vector comprises (i) a recombinant polypeptide comprising a single epitope, e.g., a single T cell epitope, e.g
- the first vector comprises (i) a recombinant polypeptide comprising a single epitope, e.g., a single T cell epitope, e.g., a single cancer-specific CD8+ epitope, e.g., a single cancer-specific CD8+ epitope comprising an amino acid sequence as set forth in any of SEQ ID NOs: 13-18, or (ii) a polynucleotide encoding a recombinant polypeptide comprising a single epitope, e.g., a single T cell epitope, e.g., a single cancer-specific CD8+ epitope, e.g., a single cancer-specific CD8+ epitope comprising an amino acid sequence as set forth in any of SEQ ID NOs: 13-18
- the second vector comprises (i) a recombinant polypeptide comprising a single epitope, e.g., a single T cell epitope, e.g
- the composition e.g., the therapeutic composition is capable of inducing production of an inflated memory CD8+ T cell response that is capable of controlling tumor growth in the subject greater than 1, day, 2 days, 5 days, 10 days, 15 days, 20 days, 25 days, 30 days, 40 days, 45 days, 50 days, 55 days, 60 days, or longer after the composition is administered.
- the composition e.g., the therapeutic composition is an immunogenic composition.
- the immunogenic composition may further comprise one or more additional active ingredients, pharmaceutically acceptable carrier, diluent, excipient or adjuvant.
- the immunogenic composition comprising a vector according to the disclosure may be used in combination with at least one other immunogenic composition comprising a vector according to the disclosure, wherein each vector encodes an identical cancer specific CD8+ T cell epitope.
- the immunogenic composition comprising a vector according to the disclosure may be used in combination with at least one other immunogenic composition comprising a vector according to the disclosure, wherein each vector encodes a different cancer specific CD8+ T cell epitope.
- the immunogenic composition comprising a first vector according to the disclosure may be administered separately, sequentially or simultaneously with an immunogenic composition comprising a second vector according to the disclosure.
- the immunogenic composition comprising a first vector according to the disclosure may be administered separately, sequentially or simultaneously with an immunogenic composition comprising a second vector described herein and an immunogenic composition comprising a third vector described herein. In some embodiments, the immunogenic composition comprising a first vector according to the disclosure may be administered separately, sequentially or simultaneously with an immunogenic composition comprising a second vector, a third vector, and a fourth vector described herein. In some embodiments, the immunogenic composition comprising a first vector according to the disclosure may be administered separately, sequentially or simultaneously with an immunogenic composition comprising a second vector, a third vector, a fourth vector, and a fifth vector described herein.
- the immunogenic composition comprising a first vector according to the disclosure may be administered separately, sequentially or simultaneously with an immunogenic composition comprising a second vector, a third vector, a fourth vector, a fifth vector, and a sixth vector described herein.
- the immunogenic composition comprising a first vector according to the disclosure may be administered separately, sequentially or simultaneously with an immunogenic composition comprising a second vector, a third vector, a fourth vector, a fifth vector, a sixth vector, and a seventh vector described herein.
- the immunogenic composition comprising a first vector according to the disclosure may be administered separately, sequentially or simultaneously with an immunogenic composition comprising a second vector, a third vector, a fourth vector, a fifth vector, a sixth vector, a seventh vector, and an eighth vector described herein.
- the use of a cocktail of vectors encoding different epitopes may result in a stronger immune response, further there may be a synergistic effect which enhances the immune response.
- the immunogenic composition comprises a cocktail of vectors encoding different epitopes, e.g., cancer-specific CD8+ epitopes.
- the composition can be in the form of a liquid, e.g., a solution, emulsion, or suspension.
- the liquid compositions of the disclosure can also include one or more of the following: sterile diluents such as water, saline solution, preferably physiological saline, Ringer’s solution, isotonic sodium chloride, fixed oils such as synthetic mono or digylcerides, polyethylene glycols, glycerin, or other solvents; antibacterial agents such as benzyl alcohol or methyl paraben; and agents for the adjustment of tonicity such as sodium chloride or dextrose.
- the composition can be enclosed in an ampoule, a disposable syringe or a multiple-dose vial made of glass, plastic or other material.
- compositions can be prepared using methodology well known in the pharmaceutical art.
- a composition intended to be administered by injection can be prepared by combining a vector of the present disclosure with water so as to form a solution.
- a surfactant can be added to facilitate the formation of a homogeneous solution or suspension.
- the disclosure provides a host cell, comprising one or more recombinant polypeptides, polynucleotides, vectors and/or the compositions described herein.
- Host cells are genetically engineered (transduced or transformed or transfected) with the vectors of this disclosure which can be, for example, a cloning vector or an expression vector.
- the vector can be, for example, in the form of a plasmid, a viral particle, a phage, etc.
- the host cell genetically engineered (transduced or transformed or transfected) with one or more vectors, e.g., one or more vectors disclosed herein.
- the host cell may be used to produce an adenoviral stock.
- the engineered host cells can be cultured in conventional nutrient media modified as appropriate for activating promoters, selecting transformants or amplifying the polynucleotides.
- the culture conditions such as temperature, pH and the like, are those previously used with the host cell selected for expression and will be apparent to a person skilled in the arts.
- Suitable host cells for expression of a polypeptide include prokaryotes, yeast, insect or higher eukaryotic cells under the control of appropriate promoters.
- Prokaryotes include gram negative or gram positive organisms, for example E. coli or bacilli.
- Higher eukaryotic cells include established cell lines of mammalian origin. Cell-free translation systems could also be employed.
- Appropriate cloning and expression vectors for use with bacterial, fungal, yeast, and mammalian cellular hosts are well known in the art (see Pouwels et al., Cloning Vectors: A Laboratory Manual, Elsevier, N.Y., 1985).
- the host cell can be mammalian for example human or mouse.
- the disclosure provides a pharmaceutical composition
- a pharmaceutical composition comprising one or more recombinant polypeptides, polynucleotides, vectors, cells, or compositions disclosed herein and optionally further comprising a pharmaceutically acceptable carrier, excipient or additive.
- pharmaceutical composition refers to a composition formulated for pharmaceutical use.
- Pharmaceutical compositions comprises an immunologically effective amount of one or more recombinant polypeptides, polynucleotides, vectors, cells, or compositions disclosed herein, and optionally one or more other components which are pharmaceutically acceptable.
- a pharmaceutical composition disclosed herein can contain at least one, at least 2, at least 3, at least, 4, at least 5, or 6 epitopes, e.g., T cell epitopes, e.g., cancer-specific CD8+ and/or CD4+ epitopes, e.g., cancer specific CD8+ T cell epitopes.
- epitopes e.g., T cell epitopes, e.g., cancer-specific CD8+ and/or CD4+ epitopes, e.g., cancer specific CD8+ T cell epitopes.
- a pharmaceutical composition disclosed herein can contain 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, or 30 epitopes, e.g., T cell epitopes, e.g., cancer-specific CD8+ and/or CD4+ epitopes, e.g., cancer specific CD8+ T cell epitopes.
- epitopes e.g., T cell epitopes, e.g., cancer-specific CD8+ and/or CD4+ epitopes, e.g., cancer specific CD8+ T cell epitopes.
- the recombinant polypeptides, polynucleotides, vectors, cells, or compositions can be formulated as separate compositions that are given at the same time or different times, or the recombinant polypeptides, polynucleotides, vectors, cells, or compositions can be given as a single composition.
- the pharmaceutical composition comprises additional agents, e.g., for specific delivery, increasing half-life, or other therapeutic compounds.
- the pharmaceutical composition may comprise one or more of dimethylsulfoxide (DMSO), dextrose, water, succinate, poly I: poly C, poly-L-lysine, carboxymethylcellulose, and/or chloride.
- a pharmaceutically acceptable carrier comprises any vehicle, such as a liquid or solid filler, diluent, excipient, manufacturing aid (e.g., lubricant, talc magnesium, calcium or zinc stearate, or steric acid), or solvent encapsulating material, involved in carrying or transporting the compound from one site (e.g., the delivery site) of the body, to another site (e.g., organ, tissue or portion of the body).
- a pharmaceutically acceptable carrier is “acceptable” in the sense of being compatible with the other ingredients of the formulation and not injurious to the tissue of the subject (e.g., physiologically compatible, sterile, physiologic pH, etc.)
- Some examples of materials which can serve as pharmaceutically-acceptable carriers include: (1) sugars, such as lactose, glucose and sucrose; (2) starches, such as corn starch and potato starch; (3) cellulose, and its derivatives, such as sodium carboxymethyl cellulose, methylcellulose, ethyl cellulose, microcrystalline cellulose and cellulose acetate; (4) powdered tragacanthin; (5) malt; (6) gelatin; (7) lubricating agents, such as magnesium stearate, sodium lauryl sulfate and talc; (8) excipients, such as cocoa butter and suppository waxes; (9) oils, such as peanut oil, cottonseed oil, safflower oil, sesame oil, olive oil, corn oil and soybean oil; (10) glycols, such as propylene glycol; (11) polyols, such as glycerin, sorbitol, mannitol and polyethylene glycol (PEG); (12) esters, such as
- wetting agents, coloring agents, release agents, coating agents, sweetening agents, flavoring agents, perfuming agents, preservative and antioxidants can also be present in the formulation.
- excipient carrier
- pharmaceutically acceptable carrier or the like are used interchangeably herein.
- compositions can comprise one or more pH buffering compounds to maintain the pH of the formulation at a predetermined level that reflects physiological pH, such as in the range of about 5.0 to about 8.0.
- the pH buffering compound used in the aqueous liquid formulation can be an amino acid or mixture of amino acids, such as histidine or a mixture of amino acids such as histidine and glycine.
- the pH buffering compound is preferably an agent which maintains the pH of the formulation at a predetermined level, such as in the range of about 5.0 to about 8.0, and which does not chelate calcium ions.
- Illustrative examples of such pH buffering compounds include, but are not limited to, imidazole and acetate ions.
- the pH buffering compound may be present in any amount suitable to maintain the pH of the formulation at a predetermined level.
- compositions can also contain one or more osmotic modulating agents, i.e., a compound that modulates the osmotic properties (e.g., tonicity, osmolality, and/or osmotic pressure) of the formulation to a level that is acceptable to the blood stream and blood cells of recipient individuals.
- the osmotic modulating agent can be an agent that does not chelate calcium ions.
- the osmotic modulating agent can be any compound known or available to those skilled in the art that modulates the osmotic properties of the formulation. One skilled in the art may empirically determine the suitability of a given osmotic modulating agent for use in the inventive formulation.
- osmotic modulating agents include, but are not limited to, salts, such as sodium chloride and sodium acetate; sugars, such as sucrose, dextrose, and mannitol; amino acids, such as glycine; and mixtures of one or more of these agents and/or types of agents.
- the osmotic modulating agent(s) may be present in any concentration sufficient to modulate the osmotic properties of the formulation.
- the pharmaceutical composition comprising one or more recombinant polypeptides, polynucleotides, vectors, cells, or compositions disclosed herein may be used in vitro, ex-vivo, or in vivo.
- the pharmaceutical composition is formulated for delivery to a subject, e.g., for inducing an immune response.
- Suitable routes of administrating the pharmaceutical composition described herein include, without limitation: topical, subcutaneous, transdermal, intradermal, intralesional, intraarticular, intraperitoneal, intravesical, transmucosal, gingival, intradental, intracochlear, transtympanic, intraorgan, epidural, intrathecal, intramuscular, intravenous, intravascular, intraosseus, periocular, intratumoral, intracerebral, and intracerebroventricular administration.
- the pharmaceutical composition described herein is administered locally to a diseased site (e.g., tumor site).
- the pharmaceutical composition described herein is administered to a subject by injection, by means of a catheter, by means of a suppository, or by means of an implant, the implant being of a porous, non-porous, or gelatinous material, including a membrane, such as a sialastic membrane, or a fiber.
- the pharmaceutical composition described herein is delivered in a controlled release system.
- a pump can be used.
- polymeric materials can be used.
- the pharmaceutical composition is formulated in accordance with routine procedures as a composition adapted for intravenous or subcutaneous administration to a subject, e.g., a human.
- pharmaceutical composition for administration by injection are solutions in sterile isotonic use as solubilizing agent and a local anesthetic such as lignocaine to ease pain at the site of the injection.
- the ingredients are supplied either separately or mixed together in unit dosage form, for example, as a dry lyophilized powder or water free concentrate in a hermetically sealed container such as an ampoule or sachets indicating the quantity of active agent.
- the pharmaceutical is to be administered by infusion, it can be dispensed with an infusion bottle containing sterile pharmaceutical grade water or saline.
- an ampoule of sterile water for injection or saline can be provided so that the ingredients can be mixed prior to administration.
- a pharmaceutical composition for systemic administration can be a liquid, e.g., sterile saline, viralsterile saline, lactated Ringer’s or Hank’s solution.
- the pharmaceutical composition can be in solid forms and re-dissolved or suspended immediately prior to use. Lyophilized forms are also contemplated.
- the pharmaceutical composition can be contained within a lipid particle or vesicle, such as a liposome or microcrystal, which is also suitable for parenteral administration.
- the particles can be of any suitable structure, such as unilamellar or plurilamellar, so long as compositions are contained therein.
- SPLP stabilized plasmid-lipid particles
- DOPE fusogenic lipid dioleoylphosphatidylethanolamine
- PEG polyethyleneglycol
- Positively charged lipids such as N41-(2,3- dioleoyloxi)propyl]-N,N,N-trimethyl-amoniummethylsulfate, or “DOTAP,” are particularly preferred for such particles and vesicles.
- the pharmaceutical composition described herein can be administered or packaged as a unit dose, for example, in reference to a pharmaceutical composition to physically discrete units suitable as unitary dosage for the subject, each unit containing a predetermined quantity of active material calculated to produce the desired therapeutic effect in association with the required diluent, i.e., carrier, or vehicle.
- the pharmaceutical composition can be provided as a pharmaceutical kit comprising (a) a container containing a compound of the invention in lyophilized form and (b) a second container containing a pharmaceutically acceptable diluent (e.g., sterile used for reconstitution or dilution of the lyophilized compound of the invention.
- a pharmaceutically acceptable diluent e.g., sterile used for reconstitution or dilution of the lyophilized compound of the invention.
- Optionally associated with such container(s) can be a notice in the form prescribed by a governmental agency regulating the manufacture, use or sale of pharmaceuticals or biological products, which notice reflects approval by the agency of manufacture, use or sale for human administration.
- Formulation of the pharmaceutical compositions described herein can be prepared by any method known or hereafter developed in the art of pharmacology. In general, such preparatory methods include the step of bringing the active ingredient(s) into association with an excipient and/or one or more other accessory ingredients, and then, if necessary and/or desirable, shaping and/or packaging the product into a desired single- or multi-dose unit.
- compositions can additionally comprise a pharmaceutically acceptable excipient, which, as used herein, includes any and all solvents, dispersion media, diluents, or other liquid vehicles, dispersion or suspension aids, surface active agents, isotonic agents, thickening or emulsifying agents, preservatives, solid binders, lubricants, and the like, as suited to the particular dosage form desired.
- a pharmaceutically acceptable excipient includes any and all solvents, dispersion media, diluents, or other liquid vehicles, dispersion or suspension aids, surface active agents, isotonic agents, thickening or emulsifying agents, preservatives, solid binders, lubricants, and the like, as suited to the particular dosage form desired.
- a formulation for intravenous administration of the recombinant polypeptides, polynucleotides, vectors, cells, or compositions of the disclosure may be in the form of a sterile injectable aqueous or non-aqueous (e.g., oleaginous) solution or suspension.
- the sterile injectable preparation may also be in a sterile injectable solution or suspension in a non-toxic parenterally-acceptable diluent or solvent, for example, a solution in 1,3 -butanediol.
- acceptable vehicles and solvents that may be employed are water, phosphate buffer solution, Ringer’s solution and isotonic sodium chloride solution.
- sterile, fixed oils may be employed as a solvent or suspending medium.
- any bland fixed oil may be employed, including synthetic mono- or diglycerides.
- fatty acids such as oleic acid may be used in the preparation of the intravenous formulation of the disclosure.
- the composition or pharmaceutical composition comprises at least two vectors as described herein.
- the vectors are identical, e.g., both adenoviral vectors.
- the vectors are different; e.g., an adenoviral vector and an AAV.
- the vectors may be provided as separate medicaments for administration at the same time or at different times to a subject in need thereof.
- the vectors may be provided as separate medicaments for administration at different times. When administered separately and at different times, the composition comprising either vector may be administered first. In some embodiments, the compositions can be administered on the same day or on different days. In some embodiments, the compositions can be administered using the same schedule or at different schedules during the treatment cycle.
- the administration of the vectors may be performed simultaneously.
- simultaneous administration is used the vectors may be formulated as separate pharmaceutical compositions.
- the at least two vectors may be formulated as a single pharmaceutical composition. .
- the at least three vectors may be formulated as a single pharmaceutical composition.
- the at least four vectors may be formulated as a single pharmaceutical composition.
- the at least five vectors may be formulated as a single pharmaceutical composition.
- the at least six vectors may be formulated as a single pharmaceutical composition.
- the at least seven vectors may be formulated as a single pharmaceutical composition.
- the at least eight vectors may be formulated as a single pharmaceutical composition.
- the composition comprises all vectors that are different.
- the composition comprises at least two identical vectors.
- the composition comprises at least three identical vectors.
- the composition comprises at least four identical vectors.
- the composition comprises at least five identical vectors.
- the composition comprises at least six identical vectors.
- the recombinant polypeptides, polynucleotides, vectors, cells, compositions, pharmaceutical compositions, or formulations disclosed herein induce an inflating memory T cell response, e.g., an inflating memory CD8+ T cell response in the subject.
- the inflating memory T cell response e.g., an inflating memory CD8+ T cell response, targets cancer cells.
- recombinant polypeptides, polynucleotides, vectors, cells, compositions, pharmaceutical compositions, or formulations disclosed herein may comprise of one or a variety of epitopes (e.g., one or a variety of epitopes described herein) targeted to an HLA type encoding an MHC of a subject’s cancer cells.
- this immunotherapy prevents T cell exhaustion while specifically targeting engineered T cells to the patient’s specific cancer HLA type to ensure an effective immune response.
- the present disclosure provides a method of producing the composition described herein comprising (i) synthesizing a nucleotide sequence encoding a single cancerspecific CD8+ T cell epitope, e.g., a single cancer-specific CD8+ T cell epitope described herein, as a sense and antisense primer; (ii) cloning the nucleotide sequence encoding the single cancerspecific CD8+ T cell epitope, e.g., the single cancer-specific CD8+ T cell epitope into a first plasmid; and (iii) cloning a sequence comprising the nucleotide sequence encoding the single cancer-specific CD8+ T cell epitope, e.g., the single cancer-specific CD8+ T cell epitope from a first plasmid into a second vector, e.g., a second vector comprising adenoviral DNA.
- Suitable cloning methods are known within the art, examples of cloning methods include but are not limited to, restriction ligations methods, Gateway cloning, Gibson assembly, ligation independent cloning. The person skilled in the art will be able to determine a suitable method to clone the sequence into the plasmid.
- the cloning method to introduce the nucleic acid sequence encoding epitope sequence into the first plasmid may be the same or different from the cloning method used to.
- the cloning method to introduce the nucleic acid sequence encoding epitope sequence into the first plasmid is selected from restriction ligations methods, Gateway cloning, Gibson assembly, ligation independent cloning.
- the cloning method to introduce the nucleic acid sequence encoding epitope into the second plasmid comprising the adenoviral DNA is selected from restriction ligations methods, Gateway cloning, Gibson assembly, ligation independent cloning.
- the second vector encodes an adenoviral vector, e.g., an adenoviral vector described herein, e.g., an adhu5 adenoviral vector.
- the present disclosure relates to a method for inducing a T cell immune response in an animal against a cancer-specific epitope, e.g., a cancer-specific CD8+ epitope, the method comprising contacting a cell with a recombinant polypeptide, polynucleotide, vector, cell, composition, pharmaceutical composition, or a formulation as described herein.
- a cancer-specific epitope e.g., a cancer-specific CD8+ epitope
- the cell may be contacted with the recombinant polypeptide, polynucleotide, vector, cell, composition, pharmaceutical composition, or the formulation in an in vitro manner, in an ex vivo manner, or in an in vivo manner. Wherein the cells are contacted with the recombinant polypeptide, polynucleotide, vector, cell, composition, pharmaceutical composition, or the formulation either in vitro or ex vivo, the cells may then be administered to a subject.
- the T cell immune response may comprise an inflating memory CD8+ T cell response.
- the present disclosure provides a method of treating cancer in a subject in need thereof comprising administering one or more recombinant polypeptides, polynucleotides, vectors, cells, compositions, pharmaceutical compositions, or formulations disclosed herein.
- the method of treating cancer in a subject in need thereof comprises administering to the subject a composition comprising: (i) a recombinant polypeptide comprising a cancer-specific CD8+ T cell epitope, or (ii) a polynucleotide encoding a recombinant polypeptide comprising a cancer-specific CD8+ T cell epitope, (iii) a vector comprising (i) or (ii), (iv) antigen presenting cells (APCs) comprising (i), (ii), or (iii), or (v) T cells stimulated with APCs comprising (i), (ii), or (iii); wherein the cancer-specific CD8+ T cell epitope is GVYDGREHTV.
- a composition comprising: (i) a recombinant polypeptide comprising a cancer-specific CD8+ T cell epitope, or (ii) a polynucleotide encoding a recombinant
- the method of treating cancer in a subject in need thereof comprises administering to the subject a composition comprising: (i) a recombinant polypeptide consisting of a cancer-specific CD8+ T cell epitope, or (ii) a polynucleotide encoding a recombinant polypeptide consisting of a cancer-specific CD8+ T cell epitope, (iii) a vector comprising (i) or (ii), (iv) antigen presenting cells (APCs) comprising (i), (ii), or (iii), or (v) T cells stimulated with APCs comprising (i), (ii), or (iii); wherein the cancer-specific CD8+ T cell epitope is GVYDGREHTV.
- a composition comprising: (i) a recombinant polypeptide consisting of a cancer-specific CD8+ T cell epitope, or (ii) a polynucleotide encoding a re
- the method of treating cancer in a subject in need thereof comprises administering to the subject a composition comprising: (i) a recombinant polypeptide comprising a cancer-specific CD8+ T cell epitope, or (ii) a polynucleotide encoding a recombinant polypeptide comprising a cancer-specific CD8+ T cell epitope, (iii) a vector comprising (i) or (ii), (iv) antigen presenting cells (APCs) comprising (i), (ii), or (iii), or (v) T cells stimulated with APCs comprising (i), (ii), or (iii); wherein the cancerspecific CD8+ T cell epitope is GVYDGREHTV and wherein the subject expresses an MHC encoded by an HLA-A*02:01 allele.
- a composition comprising: (i) a recombinant polypeptide comprising a cancer-specific CD8+ T cell epitope,
- the method of treating cancer in a subject in need thereof comprises administering to the subject a composition comprising: (i) a recombinant polypeptide consisting of a cancer-specific CD8+ T cell epitope, or (ii) a polynucleotide encoding a recombinant polypeptide consisting of a cancer-specific CD8+ T cell epitope, (iii) a vector comprising (i) or (ii), (iv) antigen presenting cells (APCs) comprising (i), (ii), or (iii), or (v) T cells stimulated with APCs comprising (i), (ii), or (iii); wherein the cancerspecific CD8+ T cell epitope is GVYDGREHTV and wherein the subject expresses an MHC encoded by an HLA-A*02:01 allele.
- a composition comprising: (i) a recombinant polypeptide consisting of a cancer-specific CD8+ T cell epi
- the method of treating cancer in a subject in need thereof comprises administering to the subject a composition comprising: (i) a recombinant polypeptide comprising a cancer-specific CD8+ T cell epitope, or (ii) a polynucleotide encoding a recombinant polypeptide comprising a cancer-specific CD8+ T cell epitope, (iii) a vector comprising (i) or (ii), (iv) antigen presenting cells (APCs) comprising (i), (ii), or (iii), or (v) T cells stimulated with APCs comprising (i), (ii), or (iii); wherein the cancer-specific CD8+ T cell epitope is KLVELEHTL.
- a composition comprising: (i) a recombinant polypeptide comprising a cancer-specific CD8+ T cell epitope, or (ii) a polynucleotide encoding a recombinant polypeptid
- the method of treating cancer in a subject in need thereof comprises administering to the subject a composition comprising: (i) a recombinant polypeptide consisting of a cancer-specific CD8+ T cell epitope, or (ii) a polynucleotide encoding a recombinant polypeptide consisting of a cancer-specific CD8+ T cell epitope, (iii) a vector comprising (i) or (ii), (iv) antigen presenting cells (APCs) comprising (i), (ii), or (iii), or (v) T cells stimulated with APCs comprising (i), (ii), or (iii); wherein the cancer-specific CD8+ T cell epitope is KLVELEHTL.
- a composition comprising: (i) a recombinant polypeptide consisting of a cancer-specific CD8+ T cell epitope, or (ii) a polynucleotide encoding a recombin
- the method of treating cancer in a subject in need thereof comprises administering to the subject a composition comprising: (i) a recombinant polypeptide comprising a cancer-specific CD8+ T cell epitope, or (ii) a polynucleotide encoding a recombinant polypeptide comprising a cancer-specific CD8+ T cell epitope, (iii) a vector comprising (i) or (ii), (iv) antigen presenting cells (APCs) comprising (i), (ii), or (iii), or (v) T cells stimulated with APCs comprising (i), (ii), or (iii); wherein the cancerspecific CD8+ T cell epitope is KLVELEHTL and wherein the subject expresses an MHC encoded by an HLA-A*02:01 allele.
- a composition comprising: (i) a recombinant polypeptide comprising a cancer-specific CD8+ T cell epitope, or (
- the method of treating cancer in a subject in need thereof comprises administering to the subject a composition comprising: (i) a recombinant polypeptide consisting of a cancer-specific CD8+ T cell epitope, or (ii) a polynucleotide encoding a recombinant polypeptide consisting of a cancer-specific CD8+ T cell epitope, (iii) a vector comprising (i) or (ii), (iv) antigen presenting cells (APCs) comprising (i), (ii), or (iii), or (v) T cells stimulated with APCs comprising (i), (ii), or (iii); wherein the cancerspecific CD8+ T cell epitope is KLVELEHTL and wherein the subject expresses an MHC encoded by an HLA-A*02:01 allele.
- a composition comprising: (i) a recombinant polypeptide consisting of a cancer-specific CD8+ T cell epitope
- the method of treating cancer in a subject in need thereof comprises administering to the subject a composition comprising: (i) a recombinant polypeptide comprising a cancer-specific CD8+ T cell epitope, or (ii) a polynucleotide encoding a recombinant polypeptide comprising a cancer-specific CD8+ T cell epitope, (iii) a vector comprising (i) or (ii), (iv) antigen presenting cells (APCs) comprising (i), (ii), or (iii), or (v) T cells stimulated with APCs comprising (i), (ii), or (iii); wherein the cancer-specific CD8+ T cell epitope is SPSSASLAL.
- a composition comprising: (i) a recombinant polypeptide comprising a cancer-specific CD8+ T cell epitope, or (ii) a polynucleotide encoding a recombinant polypeptide
- the method of treating cancer in a subject in need thereof comprises administering to the subject a composition comprising: (i) a recombinant polypeptide consisting of a cancer-specific CD8+ T cell epitope, or (ii) a polynucleotide encoding a recombinant polypeptide consisting of a cancer-specific CD8+ T cell epitope, (iii) a vector comprising (i) or (ii), (iv) antigen presenting cells (APCs) comprising (i), (ii), or (iii), or (v) T cells stimulated with APCs comprising (i), (ii), or (iii); wherein the cancer-specific CD8+ T cell epitope is SPSSASLAL.
- a composition comprising: (i) a recombinant polypeptide consisting of a cancer-specific CD8+ T cell epitope, or (ii) a polynucleotide encoding a recombinant
- the method of treating cancer in a subject in need thereof comprises administering to the subject a composition comprising: (i) a recombinant polypeptide comprising a cancer-specific CD8+ T cell epitope, or (ii) a polynucleotide encoding a recombinant polypeptide comprising a cancer-specific CD8+ T cell epitope, (iii) a vector comprising (i) or (ii), (iv) antigen presenting cells (APCs) comprising (i), (ii), or (iii), or (v) T cells stimulated with APCs comprising (i), (ii), or (iii); wherein the cancer-specific CD8+ T cell epitope is SPSSASLAL and wherein the subject expresses an MHC encoded by an HLA- B*07:02 allele and/or an HLA-B*35:03 allele.
- a composition comprising: (i) a recombinant polypeptide comprising a
- the method of treating cancer in a subject in need thereof comprises administering to the subject a composition comprising: (i) a recombinant polypeptide consisting of a cancer-specific CD8+ T cell epitope, or (ii) a polynucleotide encoding a recombinant polypeptide consisting of a cancer-specific CD8+ T cell epitope, (iii) a vector comprising (i) or (ii), (iv) antigen presenting cells (APCs) comprising
- T cells stimulated with APCs comprising (i), (ii), or (iii); wherein the cancer-specific CD8+ T cell epitope is SPSSASLAL and wherein the subject expresses an MHC encoded by an HLA-B*07:02 allele and/or an HLA-B*35:03 allele.
- the method of treating cancer in a subject in need thereof comprises administering to the subject a composition comprising: (i) a recombinant polypeptide comprising a cancer-specific CD8+ T cell epitope, or (ii) a polynucleotide encoding a recombinant polypeptide comprising a cancer-specific CD8+ T cell epitope, (iii) a vector comprising (i) or (ii), (iv) antigen presenting cells (APCs) comprising (i), (ii), or (iii), or (v) T cells stimulated with APCs comprising (i), (ii), or (iii); wherein the cancer-specific CD8+ T cell epitope is KPRPDVTNEL.
- a composition comprising: (i) a recombinant polypeptide comprising a cancer-specific CD8+ T cell epitope, or (ii) a polynucleotide encoding a recombinant poly
- the method of treating cancer in a subject in need thereof comprises administering to the subject a composition comprising: (i) a recombinant polypeptide consisting of a cancer-specific CD8+ T cell epitope, or (ii) a polynucleotide encoding a recombinant polypeptide consisting of a cancer-specific CD8+ T cell epitope, (iii) a vector comprising (i) or (ii), (iv) antigen presenting cells (APCs) comprising (i), (ii), or (iii), or (v) T cells stimulated with APCs comprising (i), (ii), or (iii); wherein the cancer-specific CD8+ T cell epitope is KPRPDVTNEL.
- a composition comprising: (i) a recombinant polypeptide consisting of a cancer-specific CD8+ T cell epitope, or (ii) a polynucleotide encoding a recomb
- the method of treating cancer in a subject in need thereof comprises administering to the subject a composition comprising: (i) a recombinant polypeptide comprising a cancer-specific CD8+ T cell epitope, or (ii) a polynucleotide encoding a recombinant polypeptide comprising a cancer-specific CD8+ T cell epitope, (iii) a vector comprising (i) or (ii), (iv) antigen presenting cells (APCs) comprising (i),
- T cells stimulated with APCs comprising (i), (ii), or (iii); wherein the cancerspecific CD8+ T cell epitope is KPRPDVTNEL and wherein the subject expresses an MHC encoded by an HLA-B*07:02 allele, an HLA-B*35:03 allele, an HLA-C*07:02 allele, or any combination thereof.
- the method of treating cancer in a subject in need thereof comprises administering to the subject a composition comprising: (i) a recombinant polypeptide consisting of a cancer-specific CD8+ T cell epitope, or (ii) a polynucleotide encoding a recombinant polypeptide consisting of a cancer-specific CD8+ T cell epitope, (iii) a vector comprising (i) or (ii), (iv) antigen presenting cells (APCs) comprising (i), (ii), or (iii), or (v) T cells stimulated with APCs comprising (i), (ii), or (iii); wherein the cancer-specific CD8+ T cell epitope is KPRPDVTNEL and wherein the subject expresses an MHC encoded by an HLA- B*07:02 allele, an HLA-B*35:03 allele, an HLA-C*07:02 allele, or any combination thereof.
- the method of treating cancer in a subject in need thereof comprises administering to the subject a composition comprising: (i) a recombinant polypeptide comprising a cancer-specific CD8+ T cell epitope, or (ii) a polynucleotide encoding a recombinant polypeptide comprising a cancer-specific CD8+ T cell epitope, (iii) a vector comprising (i) or (ii), (iv) antigen presenting cells (APCs) comprising (i), (ii), or (iii), or (v) T cells stimulated with APCs comprising (i), (ii), or (iii); wherein the cancer-specific CD8+ T cell epitope is KEFAFLEHSL.
- a composition comprising: (i) a recombinant polypeptide comprising a cancer-specific CD8+ T cell epitope, or (ii) a polynucleotide encoding a recombinant poly
- the method of treating cancer in a subject in need thereof comprises administering to the subject a composition comprising: (i) a recombinant polypeptide consisting of a cancer-specific CD8+ T cell epitope, or (ii) a polynucleotide encoding a recombinant polypeptide consisting of a cancer-specific CD8+ T cell epitope, (iii) a vector comprising (i) or (ii), (iv) antigen presenting cells (APCs) comprising (i), (ii), or (iii), or (v) T cells stimulated with APCs comprising (i), (ii), or (iii); wherein the cancer-specific CD8+ T cell epitope is KEFAFLEHSL.
- a composition comprising: (i) a recombinant polypeptide consisting of a cancer-specific CD8+ T cell epitope, or (ii) a polynucleotide encoding a recomb
- the method of treating cancer in a subject in need thereof comprises administering to the subject a composition comprising: (i) a recombinant polypeptide comprising a cancer-specific CD8+ T cell epitope, or (ii) a polynucleotide encoding a recombinant polypeptide comprising a cancer-specific CD8+ T cell epitope, (iii) a vector comprising (i) or (ii), (iv) antigen presenting cells (APCs) comprising (i), (ii), or (iii), or (v) T cells stimulated with APCs comprising (i), (ii), or (iii); wherein the cancerspecific CD8+ T cell epitope is KEFAFLEHSL and wherein the subject expresses an MHC encoded by an HLA-B*40:01 allele.
- a composition comprising: (i) a recombinant polypeptide comprising a cancer-specific CD8+ T cell epitope, or
- the method of treating cancer in a subject in need thereof comprises administering to the subject a composition comprising: (i) a recombinant polypeptide comprising a cancer-specific CD8+ T cell epitope, or (ii) a polynucleotide encoding a recombinant polypeptide comprising a cancer-specific CD8+ T cell epitope, (iii) a vector comprising (i) or (ii), (iv) antigen presenting cells (APCs) comprising (i), (ii), or (iii), or (v) T cells stimulated with APCs comprising (i), (ii), or (iii); wherein the cancerspecific CD8+ T cell epitope is KEFAFLEHSL and wherein the subject expresses an MHC encoded by an HLA-B*40:01 allele, an HLA-B*40:02 allele, an HLA-B*44:02 allele, or any combination thereof.
- a composition comprising: (
- the method of treating cancer in a subject in need thereof comprises administering to the subject a composition comprising: (i) a recombinant polypeptide consisting of a cancer-specific CD8+ T cell epitope, or (ii) a polynucleotide encoding a recombinant polypeptide consisting of a cancer-specific CD8+ T cell epitope, (iii) a vector comprising (i) or (ii), (iv) antigen presenting cells (APCs) comprising (i), (ii), or (iii), or (v) T cells stimulated with APCs comprising (i), (ii), or (iii); wherein the cancer-specific CD8+ T cell epitope is KEFAFLEHSL and wherein the subject expresses an MHC encoded by an HLA- B*40:01 allele.
- a composition comprising: (i) a recombinant polypeptide consisting of a cancer-specific CD8+ T cell epi
- the method of treating cancer in a subject in need thereof comprises administering to the subject a composition comprising: (i) a recombinant polypeptide consisting of a cancer-specific CD8+ T cell epitope, or (ii) a polynucleotide encoding a recombinant polypeptide consisting of a cancer-specific CD8+ T cell epitope, (iii) a vector comprising (i) or (ii), (iv) antigen presenting cells (APCs) comprising (i), (ii), or (iii), or (v) T cells stimulated with APCs comprising (i), (ii), or (iii); wherein the cancer-specific CD8+ T cell epitope is KEFAFLEHSL and wherein the subject expresses an MHC encoded by an HLA- B*44:02 allele.
- a composition comprising: (i) a recombinant polypeptide consisting of a cancer-specific CD8+ T cell epi
- the method of treating cancer in a subject in need thereof comprises administering to the subject a composition comprising: (i) a recombinant polypeptide comprising a cancer-specific CD8+ T cell epitope, or (ii) a polynucleotide encoding a recombinant polypeptide comprising a cancer-specific CD8+ T cell epitope, (iii) a vector comprising (i) or (ii), (iv) antigen presenting cells (APCs) comprising (i), (ii), or (iii), or (v) T cells stimulated with APCs comprising (i), (ii), or (iii); wherein the cancer-specific CD8+ T cell epitope is HELGFKVVL.
- a composition comprising: (i) a recombinant polypeptide comprising a cancer-specific CD8+ T cell epitope, or (ii) a polynucleotide encoding a recombinant
- the method of treating cancer in a subject in need thereof comprises administering to the subject a composition comprising: (i) a recombinant polypeptide consisting of a cancer-specific CD8+ T cell epitope, or (ii) a polynucleotide encoding a recombinant polypeptide consisting of a cancer-specific CD8+ T cell epitope, (iii) a vector comprising (i) or (ii), (iv) antigen presenting cells (APCs) comprising (i), (ii), or (iii), or (v) T cells stimulated with APCs comprising (i), (ii), or (iii); wherein the cancer-specific CD8+ T cell epitope is HELGFKVVL.
- a composition comprising: (i) a recombinant polypeptide consisting of a cancer-specific CD8+ T cell epitope, or (ii) a polynucleotide encoding a re
- the method of treating cancer in a subject in need thereof comprises administering to the subject a composition comprising: (i) a recombinant polypeptide comprising a cancer-specific CD8+ T cell epitope, or (ii) a polynucleotide encoding a recombinant polypeptide comprising a cancer-specific CD8+ T cell epitope, (iii) a vector comprising (i) or (ii), (iv) antigen presenting cells (APCs) comprising (i), (ii), or (iii), or (v) T cells stimulated with APCs comprising (i), (ii), or (iii); wherein the cancerspecific CD8+ T cell epitope is HELGFKVVL and wherein the subject expresses an MHC encoded by an HLA-B* 18:01 allele.
- a composition comprising: (i) a recombinant polypeptide comprising a cancer-specific CD8+ T cell epitope,
- the method of treating cancer in a subject in need thereof comprises administering to the subject a composition comprising: (i) a recombinant polypeptide comprising a cancer-specific CD8+ T cell epitope, or (ii) a polynucleotide encoding a recombinant polypeptide comprising a cancer-specific CD8+ T cell epitope, (iii) a vector comprising (i) or (ii), (iv) antigen presenting cells (APCs) comprising (i), (ii), or (iii), or (v) T cells stimulated with APCs comprising (i), (ii), or (iii); wherein the cancerspecific CD8+ T cell epitope is HELGFKVVL and wherein the subject expresses an MHC encoded by an HLA-B*40:01 allele.
- a composition comprising: (i) a recombinant polypeptide comprising a cancer-specific CD8+ T cell epitope,
- the method of treating cancer in a subject in need thereof comprises administering to the subject a composition comprising: (i) a recombinant polypeptide comprising a cancer-specific CD8+ T cell epitope, or (ii) a polynucleotide encoding a recombinant polypeptide comprising a cancer-specific CD8+ T cell epitope, (iii) a vector comprising (i) or (ii), (iv) antigen presenting cells (APCs) comprising (i), (ii), or (iii), or (v) T cells stimulated with APCs comprising (i), (ii), or (iii); wherein the cancerspecific CD8+ T cell epitope is HELGFKVVL and wherein the subject expresses an MHC encoded by an HLA-B*44:02 allele.
- a composition comprising: (i) a recombinant polypeptide comprising a cancer-specific CD8+ T cell epitope,
- the method of treating cancer in a subject in need thereof comprises administering to the subject a composition comprising: (i) a recombinant polypeptide consisting of a cancer-specific CD8+ T cell epitope, or (ii) a polynucleotide encoding a recombinant polypeptide consisting of a cancer-specific CD8+ T cell epitope, (iii) a vector comprising (i) or (ii), (iv) antigen presenting cells (APCs) comprising (i), (ii), or (iii), or (v) T cells stimulated with APCs comprising (i), (ii), or (iii); wherein the cancerspecific CD8+ T cell epitope is HELGFKVVL and wherein the subject expresses an MHC encoded by an HLA-B* 18:01 allele.
- a composition comprising: (i) a recombinant polypeptide consisting of a cancer-specific CD8+ T cell epi
- the method of treating cancer in a subject in need thereof comprises administering to the subject a composition comprising: (i) a recombinant polypeptide consisting of a cancer-specific CD8+ T cell epitope, or (ii) a polynucleotide encoding a recombinant polypeptide consisting of a cancer-specific CD8+ T cell epitope, (iii) a vector comprising (i) or (ii), (iv) antigen presenting cells (APCs) comprising (i), (ii), or (iii), or (v) T cells stimulated with APCs comprising (i), (ii), or (iii); wherein the cancerspecific CD8+ T cell epitope is HELGFKVVL and wherein the subject expresses an MHC encoded by an HLA-B*40:01 allele.
- a composition comprising: (i) a recombinant polypeptide consisting of a cancer-specific CD8+ T cell epi
- the method of treating cancer in a subject in need thereof comprises administering to the subject a composition comprising: (i) a recombinant polypeptide consisting of a cancer-specific CD8+ T cell epitope, or (ii) a polynucleotide encoding a recombinant polypeptide consisting of a cancer-specific CD8+ T cell epitope, (iii) a vector comprising (i) or (ii), (iv) antigen presenting cells (APCs) comprising (i), (ii), or (iii), or (v) T cells stimulated with APCs comprising (i), (ii), or (iii); wherein the cancerspecific CD8+ T cell epitope is HELGFKVVL and wherein the subject expresses an MHC encoded by an HLA-B *44: 02 allele.
- a composition comprising: (i) a recombinant polypeptide consisting of a cancer-specific CD8+ T cell epi
- the therapeutic composition comprises: (i) a recombinant polypeptide consisting of a cancer-specific CD8+ T cell epitope, or (ii) a polynucleotide encoding a recombinant polypeptide consisting of a cancer-specific CD8+ T cell epitope, (iii) a vector comprising (i) or (ii), (iv) antigen presenting cells (APCs) comprising
- T cells stimulated with APCs comprising (i), (ii), or (iii); wherein the cancer-specific CD8+ T cell epitope is HELGFKVVL and wherein the composition is for use in treating cancer is a subject that expresses an MHC encoded by an HLA-B*40:02 allele.
- the method of treating cancer in a subject in need thereof comprises administering: (i) a recombinant polypeptide comprising a cancer-specific CD8+ T cell epitope, or (ii) a polynucleotide encoding a recombinant polypeptide comprising a cancerspecific CD8+ T cell epitope, (iii) a vector comprising (i) or (ii), (iv) antigen presenting cells (APCs) comprising (i), (ii), or (iii), or (v) T cells stimulated with APCs comprising (i), (ii), or (iii); wherein the cancer-specific CD8+ T cell epitope is NLRPPTQEL.
- APCs antigen presenting cells
- the method of treating cancer in a subject in need thereof comprises administering: (i) a recombinant polypeptide consisting of a cancer-specific CD8+ T cell epitope, or (ii) a polynucleotide encoding a recombinant polypeptide consisting of a cancer-specific CD8+ T cell epitope, (iii) a vector comprising (i) or (ii), (iv) antigen presenting cells (APCs) comprising (i),
- the method of treating cancer in a subject in need thereof comprises administering: (i) a recombinant polypeptide comprising a cancer-specific CD8+ T cell epitope, or (ii) a polynucleotide encoding a recombinant polypeptide comprising a cancer-specific CD8+ T cell epitope, (iii) a vector comprising (i) or (ii), (iv) antigen presenting cells (APCs) comprising (i), (ii), or (iii), or (v) T cells stimulated with APCs comprising (i), (ii), or (iii); wherein the cancer-specific CD8+ T cell epitope is NLRPPTQEL and wherein the composition is for use in
- the method of treating cancer in a subject in need thereof comprises administering: (i) a recombinant polypeptide consisting of a cancer-specific CD8+ T cell epitope, or (ii) a polynucleotide encoding a recombinant polypeptide consisting of a cancer-specific CD8+ T cell epitope, (iii) a vector comprising (i) or (ii), (iv) antigen presenting cells (APCs) comprising (i), (ii), or (iii), or (v) T cells stimulated with APCs comprising (i), (ii), or (iii); wherein the cancer-specific CD8+ T cell epitope is NLRPPTQEL and wherein the composition is for use in treating cancer is a subject that expresses an MHC encoded by an HLA-B*07:02 allele, an HLA-B*35:03 allele, an HLA- C*07:02 allele, an HLA-
- the method of treating cancer in a subject in need thereof comprises administering: (i) a recombinant polypeptide comprising at least two cancer-specific CD8+ T cell epitopes, or (ii) a polynucleotide encoding a recombinant polypeptide comprising at least two cancer-specific CD8+ T cell epitopes, (iii) a vector comprising (i) or (ii), (iv) antigen presenting cells (APCs) comprising (i), (ii), or (iii), or (v) T cells stimulated with APCs comprising (i), (ii), or (iii); wherein the at least two cancer-specific CD8+ T cell epitopes are GVYDGREHTV and KLVELEHTL.
- APCs antigen presenting cells
- the method of treating cancer in a subject in need thereof comprises administering: (i) a recombinant polypeptide consisting of at least two cancer-specific CD8+ T cell epitopes, or (ii) a polynucleotide encoding a recombinant polypeptide consisting of at least two cancer-specific CD8+ T cell epitopes, (iii) a vector comprising (i) or (ii), (iv) antigen presenting cells (APCs) comprising (i), (ii), or (iii), or (v) T cells stimulated with APCs comprising (i), (ii), or (iii); wherein the at least two cancer-specific CD8+ T cell epitopes are GVYDGREHTV and KLVELEHTL.
- APCs antigen presenting cells
- the method of treating cancer in a subject in need thereof comprises administering: (i) a recombinant polypeptide comprising at least two cancer-specific CD8+ T cell epitopes, or (ii) a polynucleotide encoding a recombinant polypeptide comprising at least two cancer-specific CD8+ T cell epitopes, (iii) a vector comprising (i) or (ii), (iv) antigen presenting cells (APCs) comprising (i), (ii), or (iii), or (v) T cells stimulated with APCs comprising (i), (ii), or (iii); wherein the at least two cancer-specific CD8+ T cell epitopes are GVYDGREHTV and KLVELEHTL and wherein the subject expresses an MHC encoded by an HLA-A*02:01 allele.
- APCs antigen presenting cells
- the method of treating cancer in a subject in need thereof comprises administering: (i) a recombinant polypeptide consisting of at least two cancer-specific CD8+ T cell epitopes, or (ii) a polynucleotide encoding a recombinant polypeptide consisting of at least two cancer-specific CD8+ T cell epitopes, (iii) a vector comprising (i) or (ii), (iv) antigen presenting cells (APCs) comprising (i), (ii), or (iii), or (v) T cells stimulated with APCs comprising (i), (ii), or (iii); wherein the at least two cancer-specific CD8+ T cell epitopes are GVYDGREHTV and KLVELEHTL and wherein the subject expresses an MHC encoded by an HLA-A*02:01 allele.
- APCs antigen presenting cells
- the method of treating cancer in a subject in need thereof comprises administering: (i) a recombinant polypeptide comprising at least two cancer-specific CD8+ T cell epitopes, or (ii) a polynucleotide encoding a recombinant polypeptide comprising at least two cancer-specific CD8+ T cell epitopes, (iii) a vector comprising (i) or (ii), (iv) antigen presenting cells (APCs) comprising (i), (ii), or (iii), or (v) T cells stimulated with APCs comprising (i), (ii), or (iii); wherein the at least two cancer-specific CD8+ T cell epitopes are GVYDGREHTV and SPSSASLAL.
- APCs antigen presenting cells
- the method of treating cancer in a subject in need thereof comprises administering: (i) a recombinant polypeptide consisting of at least two cancer-specific CD8+ T cell epitopes, or (ii) a polynucleotide encoding a recombinant polypeptide consisting of at least two cancer-specific CD8+ T cell epitopes, (iii) a vector comprising (i) or (ii), (iv) antigen presenting cells (APCs) comprising (i), (ii), or (iii), or (v) T cells stimulated with APCs comprising (i), (ii), or (iii); wherein the at least two cancer-specific CD8+ T cell epitopes are GVYDGREHTV and SPSSASLAL.
- APCs antigen presenting cells
- the method of treating cancer in a subject in need thereof comprises administering: (i) a recombinant polypeptide comprising at least two cancer-specific CD8+ T cell epitopes, or (ii) a polynucleotide encoding a recombinant polypeptide comprising at least two cancer-specific CD8+ T cell epitopes, (iii) a vector comprising (i) or (ii), (iv) antigen presenting cells (APCs) comprising (i), (ii), or (iii), or (v) T cells stimulated with APCs comprising (i), (ii), or (iii); wherein the at least two cancer-specific CD8+ T cell epitopes are GVYDGREHTV and SPSSASLAL and wherein the subject expresses an MHC encoded by an HLA-A*02:01 allele, an HLA-B*07:02 allele, an HLA-B*35:03 allele, or any combination
- the method of treating cancer in a subject in need thereof comprises administering: (i) a recombinant polypeptide consisting of at least two cancer-specific CD8+ T cell epitopes, or (ii) a polynucleotide encoding a recombinant polypeptide consisting of at least two cancer-specific CD8+ T cell epitopes, (iii) a vector comprising (i) or (ii), (iv) antigen presenting cells (APCs) comprising (i), (ii), or (iii), or (v) T cells stimulated with APCs comprising (i), (ii), or (iii); wherein the at least two cancerspecific CD8+ T cell epitopes are GVYDGREHTV and SPSSASLAL and wherein the subject expresses an MHC encoded by an HLA-A*02:01 allele, an HLA-B*07:02 allele, an HLA- B*35:03 allele, or any
- the method of treating cancer in a subject in need thereof comprises administering: (i) a recombinant polypeptide comprising at least two cancer-specific CD8+ T cell epitopes, or (ii) a polynucleotide encoding a recombinant polypeptide comprising at least two cancer-specific CD8+ T cell epitopes, (iii) a vector comprising (i) or (ii), (iv) antigen presenting cells (APCs) comprising (i), (ii), or (iii), or (v) T cells stimulated with APCs comprising (i), (ii), or (iii); wherein the at least two cancer-specific CD8+ T cell epitopes are GVYDGREHTV and KPRPDVTNEL.
- APCs antigen presenting cells
- the method of treating cancer in a subject in need thereof comprises administering: (i) a recombinant polypeptide consisting of at least two cancer-specific CD8+ T cell epitopes, or (ii) a polynucleotide encoding a recombinant polypeptide consisting of at least two cancer-specific CD8+ T cell epitopes, (iii) a vector comprising (i) or (ii), (iv) antigen presenting cells (APCs) comprising (i), (ii), or (iii), or (v) T cells stimulated with APCs comprising (i), (ii), or (iii); wherein the at least two cancer-specific CD8+ T cell epitopes are GVYDGREHTV and KPRPDVTNEL.
- APCs antigen presenting cells
- the method of treating cancer in a subject in need thereof comprises administering: (i) a recombinant polypeptide comprising at least two cancer-specific CD8+ T cell epitopes, or (ii) a polynucleotide encoding a recombinant polypeptide comprising at least two cancer-specific CD8+ T cell epitopes, (iii) a vector comprising (i) or (ii), (iv) antigen presenting cells (APCs) comprising (i), (ii), or (iii), or (v) T cells stimulated with APCs comprising (i), (ii), or (iii); wherein the at least two cancer-specific CD8+ T cell epitopes are GVYDGREHTV and KPRPDVTNEL and wherein the subject expresses an MHC encoded by an HLA-A*02:01 allele, an HLA-B*07:02 allele, an HLA-B*35:03 allele, an MHC encoded
- a polynucleotide encoding a recombinant polypeptide consisting of at least two cancerspecific CD8+ T cell epitopes (iii) a vector comprising (i) or (ii), (iv) antigen presenting cells (APCs) comprising (i), (ii), or (iii), or (v) T cells stimulated with APCs comprising (i), (ii), or
- the at least two cancer-specific CD8+ T cell epitopes are GVYDGREHTV and KPRPDVTNEL and wherein the subject expresses an MHC encoded by an HLA-A*02:01 allele, an HLA-B*07:02 allele, an HLA-B*35:03 allele, an HLA-C*07:02 allele, or any combination thereof.
- the method of treating cancer in a subject in need thereof comprises administering: (i) a recombinant polypeptide comprising at least two cancer-specific CD8+ T cell epitopes, or (ii) a polynucleotide encoding a recombinant polypeptide comprising at least two cancer-specific CD8+ T cell epitopes, (iii) a vector comprising (i) or (ii), (iv) antigen presenting cells (APCs) comprising (i), (ii), or (iii), or (v) T cells stimulated with APCs comprising (i), (ii), or (iii); wherein the at least two cancer-specific CD8+ T cell epitopes are GVYDGREHTV and KEFAFLEHSL.
- APCs antigen presenting cells
- the method of treating cancer in a subject in need thereof comprises administering: (i) a recombinant polypeptide consisting of at least two cancer-specific CD8+ T cell epitopes, or (ii) a polynucleotide encoding a recombinant polypeptide consisting of at least two cancer-specific CD8+ T cell epitopes, (iii) a vector comprising (i) or (ii), (iv) antigen presenting cells (APCs) comprising (i), (ii), or (iii), or (v) T cells stimulated with APCs comprising (i), (ii), or (iii); wherein the at least two cancer-specific CD8+ T cell epitopes are GVYDGREHTV and KEFAFLEHSL.
- APCs antigen presenting cells
- the method of treating cancer in a subject in need thereof comprises administering: (i) a recombinant polypeptide comprising at least two cancer-specific CD8+ T cell epitopes, or (ii) a polynucleotide encoding a recombinant polypeptide comprising at least two cancer-specific CD8+ T cell epitopes, (iii) a vector comprising (i) or (ii), (iv) antigen presenting cells (APCs) comprising (i), (ii), or (iii), or (v) T cells stimulated with APCs comprising (i), (ii), or (iii); wherein the at least two cancer-specific CD8+ T cell epitopes are GVYDGREHTV and KEFAFLEHSL and wherein the subject expresses an MHC encoded by an HLA-A*02:01 allele, an HLA-B*40:01 allele, an HLA-B*44:02 allele, an MHC encoded
- a polynucleotide encoding a recombinant polypeptide consisting of at least two cancerspecific CD8+ T cell epitopes (iii) a vector comprising (i) or (ii), (iv) antigen presenting cells (APCs) comprising (i), (ii), or (iii), or (v) T cells stimulated with APCs comprising (i), (ii), or
- the at least two cancer-specific CD8+ T cell epitopes are GVYDGREHTV and KEFAFLEHSL and wherein the subject expresses an MHC encoded by an HLA-A*02:01 allele, an HLA-B*40:01 allele, an HLA-B*44:02 allele, an HLA-B*40:02 allele, or any combination thereof.
- the method of treating cancer in a subject in need thereof comprises administering: (i) a recombinant polypeptide comprising at least two cancer-specific CD8+ T cell epitopes, or (ii) a polynucleotide encoding a recombinant polypeptide comprising at least two cancer-specific CD8+ T cell epitopes, (iii) a vector comprising (i) or (ii), (iv) antigen presenting cells (APCs) comprising (i), (ii), or (iii), or (v) T cells stimulated with APCs comprising (i), (ii), or (iii); wherein the at least two cancer-specific CD8+ T cell epitopes are GVYDGREHTV and HELGFKVVL.
- the method of treating cancer in a subject in need thereof comprises administering: (i) a recombinant polypeptide consisting of at least two cancer-specific CD8+ T cell epitopes, or (ii) a polynucleotide encoding a recombinant polypeptide consisting of at least two cancer-specific CD8+ T cell epitopes, (iii) a vector comprising (i) or (ii), (iv) antigen presenting cells (APCs) comprising (i), (ii), or (iii), or (v) T cells stimulated with APCs comprising (i), (ii), or (iii); wherein the at least two cancer-specific CD8+ T cell epitopes are GVYDGREHTV and HELGFKVVL.
- the method of treating cancer in a subject in need thereof comprises administering: (i) a recombinant polypeptide comprising at least two cancer-specific CD8+ T cell epitopes, or (ii) a polynucleotide encoding a recombinant polypeptide comprising at least two cancer-specific CD8+ T cell epitopes, (iii) a vector comprising (i) or (ii), (iv) antigen presenting cells (APCs) comprising (i), (ii), or (iii), or (v) T cells stimulated with APCs comprising (i), (ii), or (iii); wherein the at least two cancer-specific CD8+ T cell epitopes are GVYDGREHTV and HELGFKVVL and wherein the subject expresses an MHC encoded by an HLA-A*02:01 allele, an HLA-B*18:01 allele an HLA-B*40:01 allele, an MHC encoded
- the method of treating cancer in a subject in need thereof comprises administering: (i) a recombinant polypeptide consisting of at least two cancer-specific CD8+ T cell epitopes, or (ii) a polynucleotide encoding a recombinant polypeptide consisting of at least two cancer-specific CD8+ T cell epitopes, (iii) a vector comprising (i) or (ii), (iv) antigen presenting cells (APCs) comprising (i), (ii), or (iii), or (v) T cells stimulated with APCs comprising (i), (ii), or (iii); wherein the at least two cancer-specific CD8+ T cell epitopes are GVYDGREHTV and HELGFKVVL and wherein the subject expresses an MHC encoded by an HLA-A*02:01 allele, an HLA-B*18:01 allele an HLA-B*40:01 allele
- the method of treating cancer in a subject in need thereof comprises administering: (i) a recombinant polypeptide comprising at least two cancer-specific CD8+ T cell epitopes, or (ii) a polynucleotide encoding a recombinant polypeptide comprising at least two cancer-specific CD8+ T cell epitopes, (iii) a vector comprising (i) or (ii), (iv) antigen presenting cells (APCs) comprising (i), (ii), or (iii), or (v) T cells stimulated with APCs comprising (i), (ii), or (iii); wherein the at least two cancer-specific CD8+ T cell epitopes are KLVELEHTL and SPSSASLAL.
- APCs antigen presenting cells
- the method of treating cancer in a subject in need thereof comprises administering: (i) a recombinant polypeptide consisting of at least two cancer-specific CD8+ T cell epitopes, or (ii) a polynucleotide encoding a recombinant polypeptide consisting of at least two cancer-specific CD8+ T cell epitopes, (iii) a vector comprising (i) or (ii), (iv) antigen presenting cells (APCs) comprising (i), (ii), or (iii), or (v) T cells stimulated with APCs comprising (i), (ii), or (iii); wherein the at least two cancer-specific CD8+ T cell epitopes are KLVELEHTL and SPSSASLAL.
- APCs antigen presenting cells
- the method of treating cancer in a subject in need thereof comprises administering: (i) a recombinant polypeptide comprising at least two cancer-specific CD8+ T cell epitopes, or (ii) a polynucleotide encoding a recombinant polypeptide comprising at least two cancer-specific CD8+ T cell epitopes, (iii) a vector comprising (i) or (ii), (iv) antigen presenting cells (APCs) comprising (i), (ii), or (iii), or (v) T cells stimulated with APCs comprising (i), (ii), or (iii); wherein the at least two cancer-specific CD8+ T cell epitopes are KLVELEHTL and SPSSASLAL and wherein the subject expresses an MHC encoded by an HLA-A*02:01 allele, an HLA-B*07:02 allele, an HLA-B*35:03 allele, or any combination thereof.
- the method of treating cancer in a subject in need thereof comprises administering: (i) a recombinant polypeptide consisting of at least two cancer-specific CD8+ T cell epitopes, or (ii) a polynucleotide encoding a recombinant polypeptide consisting of at least two cancer-specific CD8+ T cell epitopes, (iii) a vector comprising (i) or (ii), (iv) antigen presenting cells (APCs) comprising (i), (ii), or (iii), or (v) T cells stimulated with APCs comprising (i), (ii), or (iii); wherein the at least two cancer- specific CD8+ T cell epitopes are KLVELEHTL and SPSSASLAL and wherein the subject expresses an MHC encoded by an HLA-A*02:01 allele, an HLA-B*07:02 allele, an HLA- B*35:03 allele, or any combination
- the method of treating cancer in a subject in need thereof comprises administering: (i) a recombinant polypeptide comprising at least two cancer-specific CD8+ T cell epitopes, or (ii) a polynucleotide encoding a recombinant polypeptide comprising at least two cancer-specific CD8+ T cell epitopes, (iii) a vector comprising (i) or (ii), (iv) antigen presenting cells (APCs) comprising (i), (ii), or (iii), or (v) T cells stimulated with APCs comprising (i), (ii), or (iii); wherein the at least two cancer-specific CD8+ T cell epitopes are KLVELEHTL and KPRPDVTNEL.
- APCs antigen presenting cells
- the method of treating cancer in a subject in need thereof comprises administering: (i) a recombinant polypeptide consisting of at least two cancer-specific CD8+ T cell epitopes, or (ii) a polynucleotide encoding a recombinant polypeptide consisting of at least two cancer-specific CD8+ T cell epitopes, (iii) a vector comprising (i) or (ii), (iv) antigen presenting cells (APCs) comprising (i), (ii), or (iii), or (v) T cells stimulated with APCs comprising (i), (ii), or (iii); wherein the at least two cancer-specific CD8+ T cell epitopes are KLVELEHTL and KPRPDVTNEL.
- APCs antigen presenting cells
- the method of treating cancer in a subject in need thereof comprises administering: (i) a recombinant polypeptide comprising at least two cancer-specific CD8+ T cell epitopes, or (ii) a polynucleotide encoding a recombinant polypeptide comprising at least two cancer-specific CD8+ T cell epitopes, (iii) a vector comprising (i) or (ii), (iv) antigen presenting cells (APCs) comprising (i), (ii), or (iii), or (v) T cells stimulated with APCs comprising (i), (ii), or (iii); wherein the at least two cancer-specific CD8+ T cell epitopes are KLVELEHTL and KPRPDVTNEL and wherein the subject expresses an MHC encoded by an HLA-A*02:01 allele, an HLA-B*07:02 allele, an HLA-B*35:03 allele, an HLA
- a polynucleotide encoding a recombinant polypeptide consisting of at least two cancerspecific CD8+ T cell epitopes (iii) a vector comprising (i) or (ii), (iv) antigen presenting cells (APCs) comprising (i), (ii), or (iii), or (v) T cells stimulated with APCs comprising (i), (ii), or
- the at least two cancer-specific CD8+ T cell epitopes are KLVELEHTL and KPRPDVTNEL and wherein the subject expresses an MHC encoded by an HLA-A*02:01 allele, an HLA-B*07:02 allele, an HLA-B*35:03 allele, an HLA-C*07:02 allele, or any combination thereof.
- the method of treating cancer in a subject in need thereof comprises administering: (i) a recombinant polypeptide comprising at least two cancer-specific CD8+ T cell epitopes, or (ii) a polynucleotide encoding a recombinant polypeptide comprising at least two cancer-specific CD8+ T cell epitopes, (iii) a vector comprising (i) or (ii), (iv) antigen presenting cells (APCs) comprising (i), (ii), or (iii), or (v) T cells stimulated with APCs comprising (i), (ii), or (iii); wherein the at least two cancer-specific CD8+ T cell epitopes are KLVELEHTL and KEFAFLEHSL.
- the method of treating cancer in a subject in need thereof comprises administering: (i) a recombinant polypeptide consisting of at least two cancer-specific CD8+ T cell epitopes, or (ii) a polynucleotide encoding a recombinant polypeptide consisting of at least two cancer-specific CD8+ T cell epitopes, (iii) a vector comprising (i) or (ii), (iv) antigen presenting cells (APCs) comprising (i), (ii), or (iii), or (v) T cells stimulated with APCs comprising (i), (ii), or (iii); wherein the at least two cancer-specific CD8+ T cell epitopes are KLVELEHTL and KEFAFLEHSL.
- the method of treating cancer in a subject in need thereof comprises administering: (i) a recombinant polypeptide comprising at least two cancer-specific CD8+ T cell epitopes, or (ii) a polynucleotide encoding a recombinant polypeptide comprising at least two cancer-specific CD8+ T cell epitopes, (iii) a vector comprising (i) or (ii), (iv) antigen presenting cells (APCs) comprising (i), (ii), or (iii), or (v) T cells stimulated with APCs comprising (i), (ii), or (iii); wherein the at least two cancer-specific CD8+ T cell epitopes are KLVELEHTL and KEFAFLEHSL and wherein the subject expresses an MHC encoded by an HLA-A*02:01 allele, an HLA-B*40:01 allele, an HLA-B*44:02 allele, an HLA
- a polynucleotide encoding a recombinant polypeptide consisting of at least two cancerspecific CD8+ T cell epitopes (iii) a vector comprising (i) or (ii), (iv) antigen presenting cells (APCs) comprising (i), (ii), or (iii), or (v) T cells stimulated with APCs comprising (i), (ii), or
- the at least two cancer-specific CD8+ T cell epitopes are KLVELEHTL and KEFAFLEHSL and wherein the subject expresses an MHC encoded by an HLA-A*02:01 allele, an HLA-B*40:01 allele, an HLA-B*44:02 allele, an HLA-B*40:02 allele, or any combination thereof.
- the method of treating cancer in a subject in need thereof comprises administering: (i) a recombinant polypeptide comprising at least two cancer-specific CD8+ T cell epitopes, or (ii) a polynucleotide encoding a recombinant polypeptide comprising at least two cancer-specific CD8+ T cell epitopes, (iii) a vector comprising (i) or (ii), (iv) antigen presenting cells (APCs) comprising (i), (ii), or (iii), or (v) T cells stimulated with APCs comprising (i), (ii), or (iii); wherein the at least two cancer-specific CD8+ T cell epitopes are KLVELEHTL and HELGFKVVL.
- the method of treating cancer in a subject in need thereof comprises administering: (i) a recombinant polypeptide consisting of at least two cancer-specific CD8+ T cell epitopes, or (ii) a polynucleotide encoding a recombinant polypeptide consisting of at least two cancer-specific CD8+ T cell epitopes, (iii) a vector comprising (i) or (ii), (iv) antigen presenting cells (APCs) comprising (i), (ii), or (iii), or (v) T cells stimulated with APCs comprising (i), (ii), or (iii); wherein the at least two cancer-specific CD8+ T cell epitopes are KLVELEHTL and HELGFKVVL.
- the method of treating cancer in a subject in need thereof comprises administering: (i) a recombinant polypeptide comprising at least two cancer-specific CD8+ T cell epitopes, or (ii) a polynucleotide encoding a recombinant polypeptide comprising at least two cancer-specific CD8+ T cell epitopes, (iii) a vector comprising (i) or (ii), (iv) antigen presenting cells (APCs) comprising (i), (ii), or (iii), or (v) T cells stimulated with APCs comprising (i), (ii), or (iii); wherein the at least two cancer-specific CD8+ T cell epitopes are KLVELEHTL and HELGFKVVL and wherein the subject expresses an MHC encoded by an HLA-A*02:01 allele, an HLA-B*18:01 allele, an HLA-B*40:01 allele, an H
- the method of treating cancer in a subject in need thereof comprises administering: (i) a recombinant polypeptide consisting of at least two cancer-specific CD8+ T cell epitopes, or (ii) a polynucleotide encoding a recombinant polypeptide consisting of at least two cancer-specific CD8+ T cell epitopes, (iii) a vector comprising (i) or (ii), (iv) antigen presenting cells (APCs) comprising (i), (ii), or (iii), or (v) T cells stimulated with APCs comprising (i), (ii), or (iii); wherein the at least two cancer-specific CD8+ T cell epitopes are KLVELEHTL and HELGFKVVL and wherein the subject expresses an MHC encoded by an HLA-A*02:01 allele, an HLA-B*18:01 allele, an HLA-B*40:01 allele,
- the method of treating cancer in a subject in need thereof comprises administering: (i) a recombinant polypeptide comprising at least two cancer-specific CD8+ T cell epitopes, or (ii) a polynucleotide encoding a recombinant polypeptide comprising at least two cancer-specific CD8+ T cell epitopes, (iii) a vector comprising (i) or (ii), (iv) antigen presenting cells (APCs) comprising (i), (ii), or (iii), or (v) T cells stimulated with APCs comprising (i), (ii), or (iii); wherein the at least two cancer-specific CD8+ T cell epitopes are SPSSASLAL and KPRPDVTNEL.
- APCs antigen presenting cells
- the method of treating cancer in a subject in need thereof comprises administering: (i) a recombinant polypeptide consisting of at least two cancer-specific CD8+ T cell epitopes, or (ii) a polynucleotide encoding a recombinant polypeptide consisting of at least two cancer-specific CD8+ T cell epitopes, (iii) a vector comprising (i) or (ii), (iv) antigen presenting cells (APCs) comprising (i), (ii), or (iii), or (v) T cells stimulated with APCs comprising (i), (ii), or (iii); wherein the at least two cancer-specific CD8+ T cell epitopes are SPSSASLAL and KPRPDVTNEL.
- APCs antigen presenting cells
- the method of treating cancer in a subject in need thereof comprises administering: (i) a recombinant polypeptide comprising at least two cancer-specific CD8+ T cell epitopes, or (ii) a polynucleotide encoding a recombinant polypeptide comprising at least two cancer-specific CD8+ T cell epitopes, (iii) a vector comprising (i) or (ii), (iv) antigen presenting cells (APCs) comprising (i), (ii), or (iii), or (v) T cells stimulated with APCs comprising (i), (ii), or (iii); wherein the at least two cancer-specific CD8+ T cell epitopes are SPSSASLAL and KPRPDVTNEL and wherein the subject expresses an MHC encoded by an HLA-B*07:02 allele, an HLA-B*35:03 allele, an HLA-C*07:02 allele, or any combination thereof
- the method of treating cancer in a subject in need thereof comprises administering: (i) a recombinant polypeptide consisting of at least two cancer-specific CD8+ T cell epitopes or (ii) a polynucleotide encoding a recombinant polypeptide consisting of at least two cancer-specific CD8+ T cell epitopes, (iii) a vector comprising (i) or (ii), (iv) antigen presenting cells (APCs) comprising (i), (ii), or (iii), or (v) T cells stimulated with APCs comprising (i), (ii), or (iii); wherein the at least two cancerspecific CD8+ T cell epitopes are SPSSASLAL and KPRPDVTNEL and wherein the subject expresses an MHC encoded by an HLA-B*07:02 allele, an HLA-B*35:03 allele, an HLA- C*07:02 allele, or any combination thereof
- the method of treating cancer in a subject in need thereof comprises administering: (i) a recombinant polypeptide comprising at least two cancer-specific CD8+ T cell epitopes, or (ii) a polynucleotide encoding a recombinant polypeptide comprising at least two cancer-specific CD8+ T cell epitopes, (iii) a vector comprising (i) or (ii), (iv) antigen presenting cells (APCs) comprising (i), (ii), or (iii), or (v) T cells stimulated with APCs comprising (i), (ii), or (iii); wherein the at least two cancer-specific CD8+ T cell epitopes are SPSSASLAL and KEFAFLEHSL.
- APCs antigen presenting cells
- the method of treating cancer in a subject in need thereof comprises administering: (i) a recombinant polypeptide consisting of at least two cancer-specific CD8+ T cell epitopes, or (ii) a polynucleotide encoding a recombinant polypeptide consisting of at least two cancer-specific CD8+ T cell epitopes, (iii) a vector comprising (i) or (ii), (iv) antigen presenting cells (APCs) comprising (i), (ii), or (iii), or (v) T cells stimulated with APCs comprising (i), (ii), or (iii); wherein the at least two cancer-specific CD8+ T cell epitopes are SPSSASLAL and KEFAFLEHSL.
- APCs antigen presenting cells
- the method of treating cancer in a subject in need thereof comprises administering: (i) a recombinant polypeptide comprising at least two cancer-specific CD8+ T cell epitopes, or (ii) a polynucleotide encoding a recombinant polypeptide comprising at least two cancer-specific CD8+ T cell epitopes, (iii) a vector comprising (i) or (ii), (iv) antigen presenting cells (APCs) comprising (i), (ii), or (iii), or (v) T cells stimulated with APCs comprising (i), (ii), or (iii); wherein the at least two cancer-specific CD8+ T cell epitopes are SPSSASLAL and KEFAFLEHSL and wherein the subject expresses an MHC encoded by an HLA-B*07:02 allele, an HLA-B*35:03 allele, an HLA-B*40:01 allele, an HLA-
- the method of treating cancer in a subject in need thereof comprises administering: (i) a recombinant polypeptide consisting of at least two cancer-specific CD8+ T cell epitopes, or (ii) a polynucleotide encoding a recombinant polypeptide consisting of at least two cancer-specific CD8+ T cell epitopes, (iii) a vector comprising (i) or (ii), (iv) antigen presenting cells (APCs) comprising (i), (ii), or (iii), or (v) T cells stimulated with APCs comprising (i), (ii), or (iii); wherein the at least two cancer-specific CD8+ T cell epitopes are SPSSASLAL and KEFAFLEHSL and wherein the subject expresses an MHC encoded by an HLA-B*07:02 allele, an HLA-B*35:03 allele, an HLA-B*40:01 allele, an H
- the method of treating cancer in a subject in need thereof comprises administering: (i) a recombinant polypeptide comprising at least two cancer-specific CD8+ T cell epitopes, or (ii) a polynucleotide encoding a recombinant polypeptide comprising at least two cancer-specific CD8+ T cell epitopes, (iii) a vector comprising (i) or (ii), (iv) antigen presenting cells (APCs) comprising (i), (ii), or (iii), or (v) T cells stimulated with APCs comprising (i), (ii), or (iii); wherein the at least two cancer-specific CD8+ T cell epitopes are SPSSASLAL and HELGFKVVL.
- APCs antigen presenting cells
- the method of treating cancer in a subject in need thereof comprises administering: (i) a recombinant polypeptide consisting of at least two cancer-specific CD8+ T cell epitopes, or (ii) a polynucleotide encoding a recombinant polypeptide consisting of at least two cancer-specific CD8+ T cell epitopes, (iii) a vector comprising (i) or (ii), (iv) antigen presenting cells (APCs) comprising (i), (ii), or (iii), or (v) T cells stimulated with APCs comprising (i), (ii), or (iii); wherein the at least two cancer-specific CD8+ T cell epitopes are SPSSASLAL and HELGFKVVL.
- APCs antigen presenting cells
- the method of treating cancer in a subject in need thereof comprises administering: (i) a recombinant polypeptide comprising at least two cancer-specific CD8+ T cell epitopes, or (ii) a polynucleotide encoding a recombinant polypeptide comprising at least two cancer-specific CD8+ T cell epitopes, (iii) a vector comprising (i) or (ii), (iv) antigen presenting cells (APCs) comprising (i), (ii), or (iii), or (v) T cells stimulated with APCs comprising (i), (ii), or (iii); wherein the at least two cancer-specific CD8+ T cell epitopes are SPSSASLAL and HELGFKVVL and wherein the subject expresses an MHC encoded by an HLA-B*07:02 allele, an HLA-B*35:03 allele, an HLA-B*18:01 allele, an HLA
- the method of treating cancer in a subject in need thereof comprises administering: (i) a recombinant polypeptide consisting of at least two cancer-specific CD8+ T cell epitopes, or (ii) a polynucleotide encoding a recombinant polypeptide consisting of at least two cancer-specific CD8+ T cell epitopes, (iii) a vector comprising (i) or (ii), (iv) antigen presenting cells (APCs) comprising (i), (ii), or (iii), or (v) T cells stimulated with APCs comprising (i), (ii), or (iii); wherein the at least two cancer-specific CD8+ T cell epitopes are SPSSASLAL and HELGFKVVL and wherein the subject expresses an MHC encoded by an HLA-B*07:02 allele, an HLA-B*35:03 allele, an HLA-B*18:01 allele, an
- the method of treating cancer in a subject in need thereof comprises administering: (i) a recombinant polypeptide comprising at least two cancer-specific CD8+ T cell epitopes, or (ii) a polynucleotide encoding a recombinant polypeptide comprising at least two cancer-specific CD8+ T cell epitopes, (iii) a vector comprising (i) or (ii), (iv) antigen presenting cells (APCs) comprising (i), (ii), or (iii), or (v) T cells stimulated with APCs comprising (i), (ii), or (iii); wherein the at least two cancer-specific CD8+ T cell epitopes are KPRPDVTNEL and KEFAFLEHSL.
- APCs antigen presenting cells
- the method of treating cancer in a subject in need thereof comprises administering: (i) a recombinant polypeptide consisting of at least two cancer-specific CD8+ T cell epitopes, or (ii) a polynucleotide encoding a recombinant polypeptide consisting of at least two cancer-specific CD8+ T cell epitopes, (iii) a vector comprising (i) or (ii), (iv) antigen presenting cells (APCs) comprising (i), (ii), or (iii), or (v) T cells stimulated with APCs comprising (i), (ii), or (iii); wherein the at least two cancer-specific CD8+ T cell epitopes are KPRPDVTNEL and KEFAFLEHSL.
- APCs antigen presenting cells
- the method of treating cancer in a subject in need thereof comprises administering: (i) a recombinant polypeptide comprising at least two cancer-specific CD8+ T cell epitopes, or (ii) a polynucleotide encoding a recombinant polypeptide comprising at least two cancer-specific CD8+ T cell epitopes, (iii) a vector comprising (i) or (ii), (iv) antigen presenting cells (APCs) comprising (i), (ii), or (iii), or (v) T cells stimulated with APCs comprising (i), (ii), or (iii); wherein the at least two cancer-specific CD8+ T cell epitopes are KPRPDVTNEL and KEFAFLEHSL and wherein the subject expresses an MHC encoded by an HLA-B*07:02 allele, an HLA-B*40:01 allele, an HLA-B*44:02 allele, an H
- the method of treating cancer in a subject in need thereof comprises administering: (i) a recombinant polypeptide consisting of at least two cancer-specific CD8+ T cell epitopes, or (ii) a polynucleotide encoding a recombinant polypeptide consisting of at least two cancer-specific CD8+ T cell epitopes, (iii) a vector comprising (i) or (ii), (iv) antigen presenting cells (APCs) comprising (i), (ii), or (iii), or (v) T cells stimulated with APCs comprising (i), (ii), or (iii); wherein the at least two cancer-specific CD8+ T cell epitopes are KPRPDVTNEL and KEFAFLEHSL and wherein the subject expresses an HLA-B*07:02 allele, an HLA-B*40:01 allele, an HLA-B*44:02 allele, an HLA-B*
- the method of treating cancer in a subject in need thereof comprises administering: (i) a recombinant polypeptide comprising at least two cancer-specific CD8+ T cell epitopes, or (ii) a polynucleotide encoding a recombinant polypeptide comprising at least two cancer-specific CD8+ T cell epitopes, (iii) a vector comprising (i) or (ii), (iv) antigen presenting cells (APCs) comprising (i), (ii), or (iii), or (v) T cells stimulated with APCs comprising (i), (ii), or (iii); wherein the at least two cancer-specific CD8+ T cell epitopes are KPRPDVTNEL and HELGFKVVL.
- APCs antigen presenting cells
- the method of treating cancer in a subject in need thereof comprises administering: (i) a recombinant polypeptide consisting of at least two cancer-specific CD8+ T cell epitopes, or (ii) a polynucleotide encoding a recombinant polypeptide consisting of at least two cancer-specific CD8+ T cell epitopes, (iii) a vector comprising (i) or (ii), (iv) antigen presenting cells (APCs) comprising (i), (ii), or (iii), or (v) T cells stimulated with APCs comprising (i), (ii), or (iii); wherein the at least two cancer-specific CD8+ T cell epitopes are KPRPDVTNEL and HELGFKVVL.
- APCs antigen presenting cells
- the method of treating cancer in a subject in need thereof comprises administering: (i) a recombinant polypeptide comprising at least two cancer-specific CD8+ T cell epitopes, or (ii) a polynucleotide encoding a recombinant polypeptide comprising at least two cancer-specific CD8+ T cell epitopes, (iii) a vector comprising (i) or (ii), (iv) antigen presenting cells (APCs) comprising (i), (ii), or (iii), or (v) T cells stimulated with APCs comprising (i), (ii), or (iii); wherein the at least two cancer-specific CD8+ T cell epitopes are KPRPDVTNEL and HELGFKVVL and wherein the subject expresses an MHC encoded by an HLA-B*07:02 allele, an HLA-B*35:03 allele, an HLA-C*07:02 allele, an
- the method of treating cancer in a subject in need thereof comprises administering: (i) a recombinant polypeptide consisting of at least two cancer-specific CD8+ T cell epitopes, or (ii) a polynucleotide encoding a recombinant polypeptide consisting of at least two cancer-specific CD8+ T cell epitopes, (iii) a vector comprising (i) or (ii), (iv) antigen presenting cells (APCs) comprising (i), (ii), or (iii), or (v) T cells stimulated with APCs comprising (i), (ii), or (iii); wherein the at least two cancer-specific CD8+ T cell epitopes are KPRPDVTNEL and HELGFKVVL and wherein the subject expresses an MHC encoded by an HLA-B*07:02 allele, an HLA-B*35:03 allele, an HLA-C*07:02 allele
- the method of treating cancer in a subject in need thereof comprises administering: (i) a recombinant polypeptide comprising at least two cancer-specific CD8+ T cell epitopes, or (ii) a polynucleotide encoding a recombinant polypeptide comprising at least two cancer-specific CD8+ T cell epitopes, (iii) a vector comprising (i) or (ii), (iv) antigen presenting cells (APCs) comprising (i), (ii), or (iii), or (v) T cells stimulated with APCs comprising (i), (ii), or (iii); wherein the at least two cancer-specific CD8+ T cell epitopes are KEFAFLEHSL and HELGFKVVL.
- the method of treating cancer in a subject in need thereof comprises administering: (i) a recombinant polypeptide consisting of at least two cancer-specific CD8+ T cell epitopes, or (ii) a polynucleotide encoding a recombinant polypeptide consisting of at least two cancer-specific CD8+ T cell epitopes, (iii) a vector comprising (i) or (ii), (iv) antigen presenting cells (APCs) comprising (i), (ii), or (iii), or (v) T cells stimulated with APCs comprising (i), (ii), or (iii); wherein the at least two cancer-specific CD8+ T cell epitopes are KEFAFLEHSL and HELGFKVVL.
- the method of treating cancer in a subject in need thereof comprises administering: (i) a recombinant polypeptide comprising at least two cancer-specific CD8+ T cell epitopes, or (ii) a polynucleotide encoding a recombinant polypeptide comprising at least two cancer-specific CD8+ T cell epitopes, (iii) a vector comprising (i) or (ii), (iv) antigen presenting cells (APCs) comprising (i), (ii), or (iii), or (v) T cells stimulated with APCs comprising (i), (ii), or (iii); wherein the at least two cancer-specific CD8+ T cell epitopes are KEFAFLEHSL and HELGFKVVL and wherein the subject expresses an MHC encoded by an HLA-B* 18:01 allele, an HLA-B*40:01 allele, an HLA-B*44:02 allele, an MHC encoded
- a polynucleotide encoding a recombinant polypeptide consisting of at least two cancerspecific CD8+ T cell epitopes (iii) a vector comprising (i) or (ii), (iv) antigen presenting cells (APCs) comprising (i), (ii), or (iii), or (v) T cells stimulated with APCs comprising (i), (ii), or
- the method of treating cancer in a subject in need thereof comprises administering: (i) a recombinant polypeptide comprising at least three cancer-specific CD8+ T cell epitopes, or (ii) a polynucleotide encoding a recombinant polypeptide comprising at least three cancer-specific CD8+ T cell epitopes, (iii) a vector comprising (i) or (ii), (iv) antigen presenting cells (APCs) comprising (i), (ii), or (iii), or (v) T cells stimulated with APCs comprising (i), (ii), or (iii); wherein the at least three cancer-specific CD8+ T cell epitopes are GVYDGREHTV and KLVELEHTL and SPSSASLAL.
- the method of treating cancer in a subject in need thereof comprises administering: (i) a recombinant polypeptide consisting of at least three cancer-specific CD8+ T cell epitopes, or (ii) a polynucleotide encoding a recombinant polypeptide consisting of at least three cancer-specific CD8+ T cell epitopes, (iii) a vector comprising (i) or (ii), (iv) antigen presenting cells (APCs) comprising (i), (ii), or (iii), or (v) T cells stimulated with APCs comprising (i), (ii), or (iii); wherein the at least three cancer-specific CD8+ T cell epitopes are GVYDGREHTV and KLVELEHTL and SPSSASLAL.
- the method of treating cancer in a subject in need thereof comprises administering: (i) a recombinant polypeptide comprising at least three cancer-specific CD8+ T cell epitopes, or (ii) a polynucleotide encoding a recombinant polypeptide comprising at least three cancer-specific CD8+ T cell epitopes, (iii) a vector comprising (i) or (ii), (iv) antigen presenting cells (APCs) comprising (i), (ii), or (iii), or (v) T cells stimulated with APCs comprising (i), (ii), or (iii); wherein the at least three cancer-specific CD8+ T cell epitopes are GVYDGREHTV and KLVELEHTL and SPSSASLAL and wherein the subject expresses an MHC encoded by an HLA-A*02:01 allele, an HLA-B*07:02 allele, an HLA-B*35:03
- the method of treating cancer in a subject in need thereof comprises administering: (i) a recombinant polypeptide consisting of at least three cancer-specific CD8+ T cell epitopes, or (ii) a polynucleotide encoding a recombinant polypeptide consisting of at least three cancer-specific CD8+ T cell epitopes, (iii) a vector comprising (i) or (ii), (iv) antigen presenting cells (APCs) comprising (i), (ii), or (iii), or (v) T cells stimulated with APCs comprising (i), (ii), or (iii); wherein the at least three cancer-specific CD8+ T cell epitopes are GVYDGREHTV and KLVELEHTL and SPSSASLAL and wherein the subject expresses an MHC encoded by an HLA-A*02:01 allele, an HLA-B*07:02 allele, an HLA-B*35
- the method of treating cancer in a subject in need thereof comprises administering: (i) a recombinant polypeptide comprising at least three cancer-specific CD8+ T cell epitopes, or (ii) a polynucleotide encoding a recombinant polypeptide comprising at least three cancer-specific CD8+ T cell epitopes, (iii) a vector comprising (i) or (ii), (iv) antigen presenting cells (APCs) comprising (i), (ii), or (iii), or (v) T cells stimulated with APCs comprising (i), (ii), or (iii); wherein the at least three cancer-specific CD8+ T cell epitopes are GVYDGREHTV and KLVELEHTL and KPRPDVTNEL.
- the method of treating cancer in a subject in need thereof comprises administering: (i) a recombinant polypeptide consisting of at least three cancer-specific CD8+ T cell epitopes, or (ii) a polynucleotide encoding a recombinant polypeptide consisting of at least three cancer-specific CD8+ T cell epitopes, (iii) a vector comprising (i) or (ii), (iv) antigen presenting cells (APCs) comprising (i), (ii), or (iii), or (v) T cells stimulated with APCs comprising (i), (ii), or (iii); wherein the at least three cancer-specific CD8+ T cell epitopes are GVYDGREHTV and KLVELEHTL and KPRPDVTNEL.
- the method of treating cancer in a subject in need thereof comprises administering: (i) a recombinant polypeptide comprising at least three cancer-specific CD8+ T cell epitopes, or (ii) a polynucleotide encoding a recombinant polypeptide comprising at least three cancer-specific CD8+ T cell epitopes, (iii) a vector comprising (i) or (ii), (iv) antigen presenting cells (APCs) comprising (i), (ii), or (iii), or (v) T cells stimulated with APCs comprising (i), (ii), or (iii); wherein the at least three cancer-specific CD8+ T cell epitopes are GVYDGREHTV and KLVELEHTL and KPRPDVTNEL and wherein the subject expresses an MHC encoded by an HLA-A*02:01 allele, an HLA-B*07:02 allele, an HLA-B*35
- a polynucleotide encoding a recombinant polypeptide consisting of at least three cancerspecific CD8+ T cell epitopes (iii) a vector comprising (i) or (ii), (iv) antigen presenting cells (APCs) comprising (i), (ii), or (iii), or (v) T cells stimulated with APCs comprising (i), (ii), or
- the at least three cancer-specific CD8+ T cell epitopes are GVYDGREHTV and KLVELEHTL and KPRPDVTNEL and wherein the subject expresses an MHC encoded by an HLA-A*02:01 allele, an HLA-B*07:02 allele, an HLA-B*35:03 allele, an HLA-C*07:02 allele, or any combination thereof.
- the method of treating cancer in a subject in need thereof comprises administering: (i) a recombinant polypeptide comprising at least three cancer-specific CD8+ T cell epitopes, or (ii) a polynucleotide encoding a recombinant polypeptide comprising at least three cancer-specific CD8+ T cell epitopes, (iii) a vector comprising (i) or (ii), (iv) antigen presenting cells (APCs) comprising (i), (ii), or (iii), or (v) T cells stimulated with APCs comprising (i), (ii), or (iii); wherein the at least three cancer-specific CD8+ T cell epitopes are GVYDGREHTV and KLVELEHTL and KEFAFLEHSL.
- the method of treating cancer in a subject in need thereof comprises administering: (i) a recombinant polypeptide consisting of at least three cancer-specific CD8+ T cell epitopes, or (ii) a polynucleotide encoding a recombinant polypeptide consisting of at least three cancer-specific CD8+ T cell epitopes, (iii) a vector comprising (i) or (ii), (iv) antigen presenting cells (APCs) comprising (i), (ii), or (iii), or (v) T cells stimulated with APCs comprising (i), (ii), or (iii); wherein the at least three cancer-specific CD8+ T cell epitopes are GVYDGREHTV and KLVELEHTL and KEFAFLEHSL.
- the method of treating cancer in a subject in need thereof comprises administering: (i) a recombinant polypeptide comprising at least three cancer-specific CD8+ T cell epitopes, or (ii) a polynucleotide encoding a recombinant polypeptide comprising at least three cancer-specific CD8+ T cell epitopes, (iii) a vector comprising (i) or (ii), (iv) antigen presenting cells (APCs) comprising (i), (ii), or (iii), or (v) T cells stimulated with APCs comprising (i), (ii), or (iii); wherein the at least three cancer-specific CD8+ T cell epitopes are GVYDGREHTV and KLVELEHTL and KEFAFLEHSL and wherein the subject expresses an MHC encoded by an HLA-A*02:01 allele, an HLA-B*40:01 allele, an HLA-B*44
- a polynucleotide encoding a recombinant polypeptide consisting of at least three cancerspecific CD8+ T cell epitopes (iii) a vector comprising (i) or (ii), (iv) antigen presenting cells (APCs) comprising (i), (ii), or (iii), or (v) T cells stimulated with APCs comprising (i), (ii), or
- the at least three cancer-specific CD8+ T cell epitopes are GVYDGREHTV and KLVELEHTL and KEFAFLEHSL and wherein the subject expresses an MHC encoded by an HLA-A*02:01 allele, an HLA-B*40:01 allele, an HLA-B*44:02 allele, an HLA-B*40:02 allele, or any combination thereof.
- the method of treating cancer in a subject in need thereof comprises administering: (i) a recombinant polypeptide comprising at least three cancer-specific CD8+ T cell epitopes, or (ii) a polynucleotide encoding a recombinant polypeptide comprising at least three cancer-specific CD8+ T cell epitopes, (iii) a vector comprising (i) or (ii), (iv) antigen presenting cells (APCs) comprising (i), (ii), or (iii), or (v) T cells stimulated with APCs comprising (i), (ii), or (iii); wherein the at least three cancer-specific CD8+ T cell epitopes are GVYDGREHTV and KLVELEHTL and HELGFKVVL.
- the method of treating cancer in a subject in need thereof comprises administering: (i) a recombinant polypeptide consisting of at least three cancer-specific CD8+ T cell epitopes, or (ii) a polynucleotide encoding a recombinant polypeptide consisting of at least three cancer-specific CD8+ T cell epitopes, (iii) a vector comprising (i) or (ii), (iv) antigen presenting cells (APCs) comprising (i), (ii), or (iii), or (v) T cells stimulated with APCs comprising (i), (ii), or (iii); wherein the at least three cancer-specific CD8+ T cell epitopes are GVYDGREHTV and KLVELEHTL and HELGFKVVL.
- the method of treating cancer in a subject in need thereof comprises administering: (i) a recombinant polypeptide comprising at least three cancer-specific CD8+ T cell epitopes, or (ii) a polynucleotide encoding a recombinant polypeptide comprising at least three cancer-specific CD8+ T cell epitopes, (iii) a vector comprising (i) or (ii), (iv) antigen presenting cells (APCs) comprising (i), (ii), or (iii), or (v) T cells stimulated with APCs comprising (i), (ii), or (iii); wherein the at least three cancer-specific CD8+ T cell epitopes are GVYDGREHTV and KLVELEHTL and HELGFKVVL and wherein the subject expresses an MHC encoded by an HLA-A*02:01 allele, an HLA-B*18:01 allele, an HLA-B*
- the method of treating cancer in a subject in need thereof comprises administering: (i) a recombinant polypeptide consisting of at least three cancerspecific CD8+ T cell epitopes, or (ii) a polynucleotide encoding a recombinant polypeptide consisting of at least three cancer-specific CD8+ T cell epitopes, (iii) a vector comprising (i) or (ii), (iv) antigen presenting cells (APCs) comprising (i), (ii), or (iii), or (v) T cells stimulated with APCs comprising (i), (ii), or (iii); wherein the at least three cancer-specific CD8+ T cell epitopes are GVYDGREHTV and KLVELEHTL and HELGFKVVL and wherein the subject expresses an MHC encoded by an HLA-A*02:01 allele, an HLA-B*18:01 allele, an HLA-B
- the method of treating cancer in a subject in need thereof comprises administering: (i) a recombinant polypeptide comprising at least three cancer-specific CD8+ T cell epitopes, or (ii) a polynucleotide encoding a recombinant polypeptide comprising at least three cancer-specific CD8+ T cell epitopes, (iii) a vector comprising (i) or (ii), (iv) antigen presenting cells (APCs) comprising (i), (ii), or (iii), or (v) T cells stimulated with APCs comprising (i), (ii), or (iii); wherein the at least three cancer-specific CD8+ T cell epitopes are GVYDGREHTV and SPSSASLAL and KPRPDVTNEL.
- APCs antigen presenting cells
- the method of treating cancer in a subject in need thereof comprises administering: (i) a recombinant polypeptide consisting of at least three cancer-specific CD8+ T cell epitopes, or (ii) a polynucleotide encoding a recombinant polypeptide consisting of at least three cancer-specific CD8+ T cell epitopes, (iii) a vector comprising (i) or (ii), (iv) antigen presenting cells (APCs) comprising (i), (ii), or (iii), or (v) T cells stimulated with APCs comprising (i), (ii), or (iii); wherein the at least three cancer-specific CD8+ T cell epitopes are GVYDGREHTV and SPSSASLAL and KPRPDVTNEL.
- APCs antigen presenting cells
- the method of treating cancer in a subject in need thereof comprises administering: (i) a recombinant polypeptide comprising at least three cancer-specific CD8+ T cell epitopes, or (ii) a polynucleotide encoding a recombinant polypeptide comprising at least three cancer-specific CD8+ T cell epitopes, (iii) a vector comprising (i) or (ii), (iv) antigen presenting cells (APCs) comprising (i), (ii), or (iii), or (v) T cells stimulated with APCs comprising (i), (ii), or (iii); wherein the at least three cancer-specific CD8+ T cell epitopes are GVYDGREHTV and SPSSASLAL and KPRPDVTNEL and wherein the subject expresses an MHC encoded by an HLA-A*02:01 allele, an HLA-B*07:02 allele, an HLA-B*35:
- a polynucleotide encoding a recombinant polypeptide consisting of at least three cancerspecific CD8+ T cell epitopes (iii) a vector comprising (i) or (ii), (iv) antigen presenting cells (APCs) comprising (i), (ii), or (iii), or (v) T cells stimulated with APCs comprising (i), (ii), or
- the at least three cancer-specific CD8+ T cell epitopes are GVYDGREHTV and SPSSASLAL and KPRPDVTNEL and wherein the subject expresses an MHC encoded by an HLA-A*02:01 allele, an HLA-B*07:02 allele, an HLA-B*35:03 allele, an HLA-C*07:02 allele, or any combination thereof.
- the method of treating cancer in a subject in need thereof comprises administering: (i) a recombinant polypeptide comprising at least three cancer-specific CD8+ T cell epitopes, or (ii) a polynucleotide encoding a recombinant polypeptide comprising at least three cancer-specific CD8+ T cell epitopes, (iii) a vector comprising (i) or (ii), (iv) antigen presenting cells (APCs) comprising (i), (ii), or (iii), or (v) T cells stimulated with APCs comprising (i), (ii), or (iii); wherein the at least three cancer-specific CD8+ T cell epitopes are GVYDGREHTV and SPSSASLAL and KEFAFLEHSL.
- APCs antigen presenting cells
- the method of treating cancer in a subject in need thereof comprises administering: (i) a recombinant polypeptide consisting of at least three cancer-specific CD8+ T cell epitopes, or (ii) a polynucleotide encoding a recombinant polypeptide consisting of at least three cancer-specific CD8+ T cell epitopes, (iii) a vector comprising (i) or (ii), (iv) antigen presenting cells (APCs) comprising (i), (ii), or (iii), or (v) T cells stimulated with APCs comprising (i), (ii), or (iii); wherein the at least three cancer-specific CD8+ T cell epitopes are GVYDGREHTV and SPSSASLAL and KEFAFLEHSL.
- APCs antigen presenting cells
- the method of treating cancer in a subject in need thereof comprises administering: (i) a recombinant polypeptide comprising at least three cancer-specific CD8+ T cell epitopes, or (ii) a polynucleotide encoding a recombinant polypeptide comprising at least three cancer-specific CD8+ T cell epitopes, (iii) a vector comprising (i) or (ii), (iv) antigen presenting cells (APCs) comprising (i), (ii), or (iii), or (v) T cells stimulated with APCs comprising (i), (ii), or (iii); wherein the at least three cancer-specific CD8+ T cell epitopes are GVYDGREHTV and SPSSASLAL and KEFAFLEHSL and wherein the subject expresses an MHC encoded by an HLA-A*02:01 allele, an HLA-B*07:02 allele, an HLA-B*35:
- the method of treating cancer in a subject in need thereof comprises administering: (i) a recombinant polypeptide consisting of at least three cancer-specific CD8+ T cell epitopes, or (ii) a polynucleotide encoding a recombinant polypeptide consisting of at least three cancer-specific CD8+ T cell epitopes, (iii) a vector comprising (i) or (ii), (iv) antigen presenting cells (APCs) comprising (i), (ii), or (iii), or (v) T cells stimulated with APCs comprising (i), (ii), or (iii); wherein the at least three cancer-specific CD8+ T cell epitopes are GVYDGREHTV and SPSSASLAL and KEFAFLEHSL and wherein the subject expresses an MHC encoded by an HLA-A*02:01 allele, an HLA-B*07:02 allele, an HLA-B*
- the method of treating cancer in a subject in need thereof comprises administering: (i) a recombinant polypeptide comprising at least three cancer-specific CD8+ T cell epitopes, or (ii) a polynucleotide encoding a recombinant polypeptide comprising at least three cancer-specific CD8+ T cell epitopes, (iii) a vector comprising (i) or (ii), (iv) antigen presenting cells (APCs) comprising (i), (ii), or (iii), or (v) T cells stimulated with APCs comprising (i), (ii), or (iii); wherein the at least three cancer-specific CD8+ T cell epitopes are GVYDGREHTV and SPSSASLAL and HELGFKVVL.
- APCs antigen presenting cells
- the method of treating cancer in a subject in need thereof comprises administering: (i) a recombinant polypeptide consisting of at least three cancer-specific CD8+ T cell epitopes, or (ii) a polynucleotide encoding a recombinant polypeptide consisting of at least three cancer-specific CD8+ T cell epitopes, (iii) a vector comprising (i) or (ii), (iv) antigen presenting cells (APCs) comprising (i), (ii), or (iii), or (v) T cells stimulated with APCs comprising (i), (ii), or (iii); wherein the at least three cancer-specific CD8+ T cell epitopes are GVYDGREHTV and SPSSASLAL and HELGFKVVL.
- APCs antigen presenting cells
- the method of treating cancer in a subject in need thereof comprises administering: (i) a recombinant polypeptide comprising at least three cancer-specific CD8+ T cell epitopes, or (ii) a polynucleotide encoding a recombinant polypeptide comprising at least three cancer-specific CD8+ T cell epitopes, (iii) a vector comprising (i) or (ii), (iv) antigen presenting cells (APCs) comprising (i), (ii), or (iii), or (v) T cells stimulated with APCs comprising (i), (ii), or (iii); wherein the at least three cancer-specific CD8+ T cell epitopes are GVYDGREHTV and SPSSASLAL and HELGFKVVL and wherein the subject expresses an MHC encoded by an HLA-A*02:01 allele, an HLA-B*07:02 allele, an HLA-B*35
- the method of treating cancer in a subject in need thereof comprises administering: (i) a recombinant polypeptide consisting of at least three cancer-specific CD8+ T cell epitopes, or (ii) a polynucleotide encoding a recombinant polypeptide consisting of at least three cancer-specific CD8+ T cell epitopes, (iii) a vector comprising (i) or (ii), (iv) antigen presenting cells (APCs) comprising (i), (ii), or (iii), or (v) T cells stimulated with APCs comprising (i), (ii), or (iii); wherein the at least three cancer-specific CD8+ T cell epitopes are GVYDGREHTV and SPSSASLAL and HELGFKVVL and wherein the subject expresses an MHC encoded by an HLA-A*02:01 allele, an HLA-B*07:02 allele, an HLA-B
- the method of treating cancer in a subject in need thereof comprises administering: (i) a recombinant polypeptide comprising at least three cancer-specific CD8+ T cell epitopes, or (ii) a polynucleotide encoding a recombinant polypeptide comprising at least three cancer-specific CD8+ T cell epitopes, (iii) a vector comprising (i) or (ii), (iv) antigen presenting cells (APCs) comprising (i), (ii), or (iii), or (v) T cells stimulated with APCs comprising (i), (ii), or (iii); wherein the at least three cancer-specific CD8+ T cell epitopes are GVYDGREHTV and KPRPDVTNEL and KEFAFLEHSL.
- the method of treating cancer in a subject in need thereof comprises administering: (i) a recombinant polypeptide consisting of at least three cancer-specific CD8+ T cell epitopes, or (ii) a polynucleotide encoding a recombinant polypeptide consisting of at least three cancer-specific CD8+ T cell epitopes, (iii) a vector comprising (i) or (ii), (iv) antigen presenting cells (APCs) comprising (i), (ii), or (iii), or (v) T cells stimulated with APCs comprising (i), (ii), or (iii); wherein the at least three cancer-specific CD8+ T cell epitopes are GVYDGREHTV and KPRPDVTNEL and KEFAFLEHSL.
- the method of treating cancer in a subject in need thereof comprises administering: (i) a recombinant polypeptide comprising at least three cancer-specific CD8+ T cell epitopes, or (ii) a polynucleotide encoding a recombinant polypeptide comprising at least three cancer-specific CD8+ T cell epitopes, (iii) a vector comprising (i) or (ii), (iv) antigen presenting cells (APCs) comprising (i), (ii), or (iii), or (v) T cells stimulated with APCs comprising (i), (ii), or (iii); wherein the at least three cancer-specific CD8+ T cell epitopes are GVYDGREHTV and KPRPDVTNEL and KEFAFLEHSL and wherein the subject expresses an MHC encoded by an HLA-A*02:01 allele, an HLA-B*07:02 allele, an HLA-B*
- the method of treating cancer in a subject in need thereof comprises administering: (i) a recombinant polypeptide consisting of at least three cancer-specific CD8+ T cell epitopes, or (ii) a polynucleotide encoding a recombinant polypeptide consisting of at least three cancer-specific CD8+ T cell epitopes, (iii) a vector comprising (i) or (ii), (iv) antigen presenting cells (APCs) comprising (i), (ii), or (iii), or (v) T cells stimulated with APCs comprising (i), (ii), or (iii); wherein the at least three cancer-specific CD8+ T cell epitopes are GVYDGREHTV and KPRPDVTNEL and KEFAFLEHSL and wherein the subject expresses an MHC encoded by an HLA-A*02:01 allele, an HLA-B*07:02 allele, an HLA-
- the method of treating cancer in a subject in need thereof comprises administering: (i) a recombinant polypeptide comprising at least three cancer-specific CD8+ T cell epitopes, or (ii) a polynucleotide encoding a recombinant polypeptide comprising at least three cancer-specific CD8+ T cell epitopes, (iii) a vector comprising (i) or (ii), (iv) antigen presenting cells (APCs) comprising (i), (ii), or (iii), or (v) T cells stimulated with APCs comprising (i), (ii), or (iii); wherein the at least three cancer-specific CD8+ T cell epitopes are GVYDGREHTV and KPRPDVTNEL and HELGFKVVL.
- the method of treating cancer in a subject in need thereof comprises administering: (i) a recombinant polypeptide consisting of at least three cancer-specific CD8+ T cell epitopes, or (ii) a polynucleotide encoding a recombinant polypeptide consisting of at least three cancer-specific CD8+ T cell epitopes, (iii) a vector comprising (i) or (ii), (iv) antigen presenting cells (APCs) comprising (i), (ii), or (iii), or (v) T cells stimulated with APCs comprising (i), (ii), or (iii); wherein the at least three cancer-specific CD8+ T cell epitopes are GVYDGREHTV and KPRPDVTNEL and HELGFKVVL.
- the method of treating cancer in a subject in need thereof comprises administering: (i) a recombinant polypeptide comprising at least three cancer-specific CD8+ T cell epitopes, or (ii) a polynucleotide encoding a recombinant polypeptide comprising at least three cancer-specific CD8+ T cell epitopes, (iii) a vector comprising (i) or (ii), (iv) antigen presenting cells (APCs) comprising (i), (ii), or (iii), or (v) T cells stimulated with APCs comprising (i), (ii), or (iii); wherein the at least three cancer-specific CD8+ T cell epitopes are GVYDGREHTV and KPRPDVTNEL and HELGFKVVL and wherein the subject expresses an MHC encoded by an HLA-A*02:01 allele, an HLA-B*07:02 allele, an HLA-B
- a polynucleotide encoding a recombinant polypeptide consisting of at least three cancerspecific CD8+ T cell epitopes (iii) a vector comprising (i) or (ii), (iv) antigen presenting cells (APCs) comprising (i), (ii), or (iii), or (v) T cells stimulated with APCs comprising (i), (ii), or
- the at least three cancer-specific CD8+ T cell epitopes are GVYDGREHTV and KPRPDVTNEL and HELGFKVVL and wherein the subject expresses an MHC encoded by an HLA-A*02:01 allele, an HLA-B *07: 02 allele, an HLA-B*35:03 allele, an HLA-C*07:02 allele, an HLA-B*40:01 allele, an HLA-B *44: 02 allele, an HLA-B *40: 02 allele, an HLA-B* 18:01 allele, or any combination thereof.
- the method of treating cancer in a subject in need thereof comprises administering: (i) a recombinant polypeptide comprising at least three cancer-specific CD8+ T cell epitopes, or (ii) a polynucleotide encoding a recombinant polypeptide comprising at least three cancer-specific CD8+ T cell epitopes, (iii) a vector comprising (i) or (ii), (iv) antigen presenting cells (APCs) comprising (i), (ii), or (iii), or (v) T cells stimulated with APCs comprising (i), (ii), or (iii); wherein the at least three cancer-specific CD8+ T cell epitopes are GVYDGREHTV and KPRPDVTNEL and KEFAFLEHSL.
- the method of treating cancer in a subject in need thereof comprises administering: (i) a recombinant polypeptide consisting of at least three cancer-specific CD8+ T cell epitopes, or (ii) a polynucleotide encoding a recombinant polypeptide consisting of at least three cancer-specific CD8+ T cell epitopes, (iii) a vector comprising (i) or (ii), (iv) antigen presenting cells (APCs) comprising (i), (ii), or (iii), or (v) T cells stimulated with APCs comprising (i), (ii), or (iii); wherein the at least three cancer-specific CD8+ T cell epitopes are GVYDGREHTV and KEFAFLEHSL and HELGFKVVL.
- the method of treating cancer in a subject in need thereof comprises administering: (i) a recombinant polypeptide comprising at least three cancer-specific CD8+ T cell epitopes, or (ii) a polynucleotide encoding a recombinant polypeptide comprising at least three cancer-specific CD8+ T cell epitopes, (iii) a vector comprising (i) or (ii), (iv) antigen presenting cells (APCs) comprising (i), (ii), or (iii), or (v) T cells stimulated with APCs comprising (i), (ii), or (iii); wherein the at least three cancer-specific CD8+ T cell epitopes are GVYDGREHTV and KEFAFLEHSL and HELGFKVVL and wherein the subject expresses an MHC encoded by an HLA-A*02:01 allele, an HLA-B*40:01 allele, an HLA-B
- the method of treating cancer in a subject in need thereof comprises administering: (i) a recombinant polypeptide consisting of at least three cancerspecific CD8+ T cell epitopes, or (ii) a polynucleotide encoding a recombinant polypeptide consisting of at least three cancer-specific CD8+ T cell epitopes, (iii) a vector comprising (i) or (ii), (iv) antigen presenting cells (APCs) comprising (i), (ii), or (iii), or (v) T cells stimulated with APCs comprising (i), (ii), or (iii); wherein the at least three cancer-specific CD8+ T cell epitopes are GVYDGREHTV and KEFAFLEHSL and HELGFKVVL and wherein the subject expresses an MHC encoded by an HLA-A*02:01 allele, an HLA-B*40:01 allele, an HLA-
- the method of treating cancer in a subject in need thereof comprises administering: (i) a recombinant polypeptide comprising at least three cancer-specific CD8+ T cell epitopes, or (ii) a polynucleotide encoding a recombinant polypeptide comprising at least three cancer-specific CD8+ T cell epitopes, (iii) a vector comprising (i) or (ii), (iv) antigen presenting cells (APCs) comprising (i), (ii), or (iii), or (v) T cells stimulated with APCs comprising (i), (ii), or (iii); wherein the at least three cancer-specific CD8+ T cell epitopes are KLVELEHTL and SPSSASLAL and KPRPDVTNEL.
- the method of treating cancer in a subject in need thereof comprises administering: (i) a recombinant polypeptide consisting of at least three cancer-specific CD8+ T cell epitopes, or (ii) a polynucleotide encoding a recombinant polypeptide consisting of at least three cancer-specific CD8+ T cell epitopes, (iii) a vector comprising (i) or (ii), (iv) antigen presenting cells (APCs) comprising (i), (ii), or (iii), or (v) T cells stimulated with APCs comprising (i), (ii), or (iii); wherein the at least three cancer-specific CD8+ T cell epitopes are KLVELEHTL and SPSSASLAL and KPRPDVTNEL.
- the method of treating cancer in a subject in need thereof comprises administering: (i) a recombinant polypeptide comprising at least three cancer-specific CD8+ T cell epitopes, or (ii) a polynucleotide encoding a recombinant polypeptide comprising at least three cancer-specific CD8+ T cell epitopes, (iii) a vector comprising (i) or (ii), (iv) antigen presenting cells (APCs) comprising (i), (ii), or (iii), or (v) T cells stimulated with APCs comprising (i), (ii), or (iii); wherein the at least three cancer-specific CD8+ T cell epitopes are KLVELEHTL and SPSSASLAL and KPRPDVTNEL and wherein the subject expresses an MHC encoded by an HLA-A*02:01 allele, an HLA-B*07:02 allele, an HLA-B*35:03 all
- a polynucleotide encoding a recombinant polypeptide consisting of at least three cancerspecific CD8+ T cell epitopes (iii) a vector comprising (i) or (ii), (iv) antigen presenting cells (APCs) comprising (i), (ii), or (iii), or (v) T cells stimulated with APCs comprising (i), (ii), or
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Abstract
La divulgation concerne des méthodes de traitement du cancer chez un sujet humain comprenant l'administration d'un polypeptide recombinant contenant un épitope de lymphocyte T CD8+ spécifique du cancer. Les peptides reconnus par des molécules du complexe majeur d'histocompatibilité (CMH) peuvent activer une réponse immunitaire des lymphocytes T pour cibler des cellules cancéreuses chez un sujet. La présente divulgation concerne également des épitopes de lymphocytes T CD8+ spécifiques du cancer restreints à des molécules du CMH exprimées par des allèles HLA spécifiques chez un sujet. La présente divulgation concerne en outre une composition codant pour le polypeptide recombinant qui peut de déclencher une réponse d'inflation des lymphocytes T CD8+ à mémoire.
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US5585362A (en) | 1989-08-22 | 1996-12-17 | The Regents Of The University Of Michigan | Adenovirus vectors for gene therapy |
US5350674A (en) | 1992-09-04 | 1994-09-27 | Becton, Dickinson And Company | Intrinsic factor - horse peroxidase conjugates and a method for increasing the stability thereof |
US6114140A (en) | 1994-05-03 | 2000-09-05 | Cold Spring Harbor Laboratory | DNA encoding density enhanced protein tyrosine phosphatases |
US5786464A (en) | 1994-09-19 | 1998-07-28 | The General Hospital Corporation | Overexpression of mammalian and viral proteins |
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