WO2017177204A1

WO2017177204A1 - Leveraging immune memory from common childhood vaccines to fight disease

Info

Publication number: WO2017177204A1
Application number: PCT/US2017/026719
Authority: WO
Inventors: Patrick Ho; Ravi KOLLA
Original assignee: La Jolla Institute For Allergy And Immunology
Priority date: 2016-04-09
Filing date: 2017-04-07
Publication date: 2017-10-12

Abstract

Presented herein are novel methods of treating cancer, which methods result in the expression of peptide antigens on a cancer. The peptide antigens are selected to initiate a recall immune response in a subject (e.g., a pre-existing immune response (memory response) that may have been induced by a prior vaccination or infection), which immune response is directed toward the cancer. In certain embodiments, the methods herein are used in combination with existing cancer therapies.

Description

LEVERAGING IMMUNE MEMORY

FROM COMMON CHILDHOOD VACCINES TO FIGHT DISEASE

RELATED PATENT APPLICATIONS

[0001] This patent application claims the benefit of U.S. Provisional Patent Application No. 62/320,488 filed on April 9, 2016, entitled LEVERAGING IMMUNE MEMORY FROM COMMON CHILDHOOD VACCINES TO FIGHT DISEASE, naming Patrick Ho and Ravi Kolla as inventors, and International Patent Application No. PCT/US2016/068147 filed on December 21, 2016, entitled LEVERAGING IMMUNE MEMORY FROM COMMON CHILDHOOD VACCINES TO FIGHT DISEASE, naming Patrick H. Ho and Ravi Kolla as inventors. The entire content of the foregoing patent applications is incorporated herein by reference, including all text, tables and drawings.

REFERENCE TO A "SEQUENCE LISTING," A TABLE, OR A COMPUTER PROGRAM LISTING APPENDIX

Sequence Listing file Name: 2015-121-04_ST25.txt

Sequence Listing file Size: 122 KB

The entire contents of the sequence listing are hereby expressly incorporated by reference.

FIELD OF INVENTION

[0002] The present invention relates to the field of disease treatment. In particular the present invention relates to the implementation of treatments for disease, from the approach of targeting pre-existing human immunity as a vehicle to specifically target and destroy target cells. BACKGROUND

[0003] Effective immunity against a pathogen entails (i) the development of highly specific, neutralizing and non-self reactive antibodies and T cells and (ii) results in the development of immune memory cells that patrol the body and provide life long protection. Immune memory cells are uniquely positioned to rapidly and robustly expand and neutralize a specific pathogen if repeated exposure occurs.

[0004] Vaccines provide a mechanism to promote safe development of long-lived immune memory against a pathogen(s) by avoiding deleterious effects of actual pathogen infection. A number of vaccines are routinely administered to children to prevent the contraction of debilitating infectious diseases and immune memory from these vaccines can be measured decades following administration.

[0005] It is known in the art that T cells, including CDS and CD4 cytotoxic T cells, play a key role in the defense against intracellular pathogens and tumor cells. T-cell immune responses are driven by the recognition of foreign peptides presented by major histocompatibility complex class I and class II (MHC I and MHC II) molecules at the cell surface. The identification of these peptides (T-cell epitopes) is therefore important for understanding disease pathogenesis and etiology as well as for vaccine design. T-cell response has been implicated in providing vaccine-mediated protection. However few T- cell epitopes from vaccines have been identified.

[0006] Current popular approaches in immunotherapy utilize cellular targets that illicit immune responses against cancer and non-cancers alike (CAR-T, Rituximab, etc.). Developing therapies to target cancer-specific antigens requires the identification of neo- antigens, self-proteins which have undergone mutation to allow recognition by the immune system. These approaches are promising, however they present possible issues with tolerance and risk of autoimmunity.

[0007] In addition, there exists in the art current immunotherapies that utilize cellular targets that are relatively widely expressed throughout the body and are not pointedly specific to a particular cancer. In this relatively broader approach, the idea is to eradicate as many of the cells that present these wide markers, which naturally include healthy and cancerous cells. This blanket approach results in the immune response attacking cells that are both cancerous and non cancerous, resulting in deleterious side effects and in many instances the patient may no longer be able to continue therapy due to negative side effects outweighing the potential benefits. The upregulation of the immune system in an attempt to equip the body's own immune system with fighter cells to attack cancer cells, has significant risk associated with inducing autoimmunity. In particular instances, whereby the treatment induces upregulation of the immune response, the upregulated state translates into the body's own immune system recognizing its own cells as foreign and begins launching an attack on its own healthy cells. A further problem with existing therapies is the risk associated with tissues beginning to build tolerance to the administered therapy whereby mutations enable cancer cells to bypass the therapeutic agent and proliferate, and they not only become unresponsive to the treatment but potentially further create an environment whereby no other alternative therapies are available. 08] Based on the foregoing, there is a need in the art for methods to target immunotherapies to specific disease cells without targeting healthy cells or significantly minimizing the effect on healthy cells and is not reliant upon antigens or epitopes of considerable homology to self, for example, a cancer immunotherapy method that provides an immune response specifically targeted to cancer cells that does not target healthy cells. Increasing evidence regarding checkpoint inhibitor targeting therapies (e.g., anti-CTLA4, anti-PDl or anti-PDL-1) shows reduced utility in cancers of low mutational burden. Unlike current treatments that target a broad range of immune response cells, which may or may not translate into the desired effect on the specific disease cells, the present invention discloses a treatment that has a targeted approach towards known epitopes recognized by the immune system from previous immunity. This approach has significant implications for patient care and treatment success by promoting more rapid, non-self, and targeted cytolytic activity. SUMMARY

[0009] In certain aspects, presented herein is a method of treating cancer comprising, a) providing a subject having or suspected of having a cancer and b) administering a vector (e.g., viral vector such as adenovirus, vaccinia or plasmid DNA) to the subject, wherein the vector directs expression of one or more peptide antigens on a target cell of the subject and wherein a memory or recall immune response is elicited against the one or more peptide antigens. In certain aspects, presented herein is a method of treating cancer comprising a) providing a subject having or suspected of having a cancer; and b) administering a composition to the subject, wherein the composition comprises one or more peptide antigen, wherein a memory or recall immune response is elicited against the one or more peptide antigens. In some embodiments, prior to the administering of (b), the subject was vaccinated against a pathogen, non-limiting examples of which include a vaccination against chickenpox, measles, mumps, rubella, shingles/varicella zoster or polio. In certain embodiments a subject is vaccinated with another suitable live-attenuated or inactivated pathogen, or pathogen antigen(s). In some embodiments, prior to the administering of (b), the subject was vaccinated with at least one of the one or more peptides selected from Table 1, or one or more other antigens derived from a pathogen. The subject may have been vaccinated or re-vaccinated 1 day, 1 month, 6 months, or 1 year to 100 years prior to administering of (b). Accordingly, in certain aspects, the administering of (b) elicits a recall immune response in the subject, wherein the recall immune response is directed against the target cell and/or at least one of the one or more peptide antigens.

[0010] In certain aspects the one or more peptide antigens bind to MHC class I or MHC class II and can recall CD8 T-cell and/or CD4 T-cell responses.

[0011] In some aspects, the subject is further administered an anti-cancer therapy.

The anti-cancer therapy may be administered prior to, concurrently with and/or after the administering of vector or peptides of (b). The anti -cancer therapy can be any suitable therapy. In some embodiments, the anti-cancer therapy comprises surgical resection. In some embodiments, the anti-cancer therapy comprises a radiation therapy, chemotherapy or an immunotherapy. In some embodiments, a radiation therapy comprises external beam radiation, proton therapy, or internal radiation therapy. In some embodiments, an immunotherapy comprises chimeric antigen receptor (CAR)-T immunotherapy. CAR-T immunotherapy sometimes comprises administering CAR T-cells configured to specifically bind to and kill the target cell. In some embodiments, an immunotherapy comprises administering an antibody or antibody fragment that specifically binds to a cell-surface antigen, non-limiting examples of which include CD20, CD30, CD33, CD52, CD 138, CD274, CD279, PD-L1, CTLA-4, programmed cell death 1 (PD-1), CD33, EGFR, ERBB2 (CD340), ERBB3, VEGF, VEGFR, GM-2, gp-100, EPCAM, CD19, CD3, CEA, gpA33, mucins, TAG-72, CAIX, PSMA, folate-binding protein, GD2, GD3, Integrin aVp3, Integrin α5β 1, IGF1R, EPHA3, TRAILR1, TRAILR2, RA KL, FAP or Tenascin. In some embodiments, the antibody may be bi-specific and may bind to two cell surface antigens. In some embodiments, the immunotherapy comprises administering an antibody or T-cell that specifically binds a checkpoint blocker. In some embodiments, an immunotherapy comprises administering an antibody or antibody fragment that specifically binds to a tumor marker.

[0012] In some aspects a peptide antigen described herein is derived from a pathogen (e.g., a peptide or protein expressed by a pathogen). In some aspects, the one or more peptide antigens are selected from a peptide listed in Table 1, or a subsequence, homologue, variant or derivative thereof.

[0013] In some embodiments, a target cell is a cell that is or has been infected with a pathogen. For example, many types of cancers are induced or caused by a previous infection by a pathogen. For example, a target cell may be a cell that is or has been infected with a virus, bacteria, parasite or protozoa. In some embodiments, a target cell is not infected with a pathogen.

[0014] A pathogen can be a human pathogen and may be a virus, fungus, bacteria, parasite or protozoa. In some embodiments, a pathogen is a non-human pathogen, or the peptide antigen is conserved between human and another species, or wherein the peptide antigen cross-reacts between human and another species. In some embodiments a pathogen is a virus, non-limiting examples of which include a virus of the order

Flaviviridae, Retroviridae, Orthomyxoviridae, Arenaviridae, or Mononegavirales, or a virus of the family Togaviridae, Reoviridae, picornaviridae, herpesviridae or Bunyaviridae.

[0015] In certain aspects, a target cell is a cancer cell or neoplastic cell. In some

embodiments, a target cell is a metastatic cancerous cell. Non-limiting examples of a cancer cell, metastatic cancerous cell or neoplastic cell include cells of a carcinoma, sarcoma, neuroblastoma, cervical cancer cell, hepatocellular cancer cell, bladder cancer cell, mesothelioma, glioblastoma, myeloma, lymphoma, neoplastic lymphocyte, adenoma, adenocarcinoma, glioma, glioblastoma, retinoblastoma, astrocytoma, oligodendrocytoma, meningioma, melanoma, lymphosarcoma, liposarcoma, osteosarcoma, chondrosarcoma, leiomyosarcoma, rhabdomyosarcoma or fibrosarcoma.

[0016] In some aspects, a subject is a mammal. In some aspects a subject is a non- human mammal. In some aspects, a subject is a human. In some embodiments, wherein prior to the administering of a vector or peptide of (b), a subject was infected with the pathogen, thereby inducing, eliciting or promoting a recall immune response in the subject to certain pathogen antigens.

[0017] In some aspects, a subject has, or is suspected of having a cancer. Non- limiting examples of a cancer include a hematological and solid tumors, a neoplasia derived from lung, thyroid, head or neck, nasopharynx, throat, nose, sinus, brain, spine, breast, adrenal gland, pituitary gland, thyroid, lymph, mouth, esophagus, stomach, duodenum, ileum, jejunum intestine, colon, rectum, uterus, urethra, ovary, cervix, endometrium, bladder, testicle, penis, prostate, kidney, pancreas, liver, bone, bone marrow, lymph, blood, muscle, or skin. Other non-liming examples of a cancer include a carcinoma, sarcoma, neuroblastoma, hepatocellular cancer, mesothelioma, glioblastoma, myeloma, lymphoma, myeloma, leukemia, adenoma, adenocarcinoma, glioma, glioblastoma, retinoblastoma, astrocytoma, oligodendrocytoma, meningioma, melanoma, cervical cancer, breast cancer, liver cancer, pancreatic cancer, brain cancer, lung cancer, skin cancer, ovarian cancer, and testicular cancer. In certain embodiments, a cancer is an infection-induced cancer non-limiting examples of which include a hepatocellular carcinoma, cervical cancer, head and neck squamous cell carcinoma, adult T-cell leukemia/lymphoma, Burkitt lymphoma, Merkel cell carcinoma, kaposi sarcoma, bladder cancer and gastric cancer. In some embodiments, a cancer comprises a low mutational burden. Non-limiting examples of a cancer comprising a low mutational burden include pilocytic astrocytoma, ALL, medulloblastoma, kidney chromophobe, thyroid, CLL, neuroblastoma, glioblastoma, and pancreatic cancer.

[0018] In some aspects, a method herein comprises administering a vector that

selectively directs expression of one or more peptide antigens on a target cell. In some embodiments, a vector directs expression of the one or more peptide antigens on the cell surface of the target cell. In some embodiments, the one or more peptide antigens are expressed or presented on the cell surface of the target cell. Presentation of a peptide antigen on the surface of a cell may include co-expression of a peptide in the presence of TAP (transporter associated with antigen processing). In some embodiments, a vector comprises a nucleic acid encoding one or more non-self-peptide antigens (e.g., one or more of the antigens of Table 1). In some embodiments, a vector comprises a promoter operatively linked to a nucleic acid encoding the one or more peptides. A promoter of a vector is sometimes inducible by a factor, for example a transcription factor derived from a pathogen, a mutated human protein, and/or one or more viral proteins. In certain embodiments, the promoter is selectively induced in tumor cells. In certain embodiments, a factor is a viral transcription factor or a factor that is selectively expressed in tumor cells.

[0019] In certain aspects, the administering of a vector or protein of (b) comprises administering nano-carriers, micro-carriers, microparticles, nanoparticles, liposomes, exosomes or recombinant virus to the subject, where the microparticles, nanoparticles, liposomes, exosomes or recombinant virus may comprise a vector or one or more peptides. In certain aspects, the administering of a vector or protein of (b) comprises selectively delivering nano-carriers, micro-carriers, microparticles, nanoparticles, liposomes, exosomes or recombinant virus to a target cell. In some embodiments, the administering of a vector of (b) comprises administering a nucleic acid to the subject, wherein the nucleic acid comprises the vector. Non-limiting examples of a vector include a plasmid, a linear nucleic acid molecule or a replicating or non-replicating viral vector. In some embodiments, a vector comprises a CRISPR element, and/or the vector is configured to express (CRISPR-associated protein-9 nuclease) CAS9. In some embodiment, a vector is integrated into the target cell by a method comprising CRISPR and (CRISPR-associated protein-9 nuclease) CAS9.

[0020] In some aspects, the administering comprises direct intra-tumoral injection. In some aspects, the administering comprises intravenous injection, intraperitoneal injection, subcutaneous injection, intramuscular injection, intravesical or intrathecal injection.

[0021] In certain aspects of a method herein, after the administering of b), the method further comprises c) initiating, eliciting, promoting, or enhancing an immune response in the subject, wherein the immune response is directed against the target cell and/or target antigen. In some embodiments, the eliciting of (c) comprises initiating, eliciting, promoting or enhancing a recall response in the subject to the one or more peptide antigens. In certain embodiments, the eliciting of (c) comprises administering a vaccine to the subject. In certain embodiments, a vaccine is selected from a vaccine for chickenpox, measles, mumps, rubella, and polio. In certain embodiments, the eliciting of (c) comprises administering a pharmaceutical composition to the subject, wherein the pharmaceutical composition comprises at least one of the one or more of the peptide antigens. In some embodiments, the pharmaceutical composition comprises an adjuvant. In certain embodiments, the eliciting of (c) comprises administering an agent that modulates an immune response in the subject. In some embodiments, the agent increases, enhances, promotes or elicits an innate immune response. In certain embodiments, the agent comprises an immune checkpoint blocker. In certain embodiments, the agent increases, enhances, promotes or elicits a recall immune response. In certain

embodiments, the agent comprises an antibody. In certain embodiments, the antibody specifically binds to the one or more peptide antigens. In some embodiments, the agent comprises a nucleic acid, synthetic chemical, or small molecule.

[0022] In certain aspects, a method herein further comprising administering a

checkpoint blocker, or providing TAP (transporter associated with antigen processing) to the target cell, wherein TAP promotes peptide epitope:MHC expression. Other peptide transporter can be provided such as the antennapedia homeodomain peptide to promote peptide:MHC binding or expression. [0023] In some aspects a composition herein comprises an adjuvant, exosomes, microparticles, nanoparticles, and/or liposomes. In some embodiments, the

microparticles, nanoparticles, or liposomes are configured to selectively deliver one or more peptide antigens to a target cell. In some embodiments, a composition is a pharmaceutical composition or pharmaceutical formulation comprising one or more peptides (e.g., a peptide listed in Table 1). In some embodiments, a composition (e.g., a pharmaceutical composition) comprises a vector configured to direct expression of one or more peptide antigens on a target cell of a subject, wherein the one or more peptide antigens is selected from a peptide listed in Table 1.

[0024] In an embodiment, the present invention provides methods and compositions for eliciting an immune response against target cells. In an embodiment, known or predicted antigens from vaccines or other developed immunity are either engineered to or serve as tags for the targeted cells so as to provide a targeted identification method for the target cells that are recognized by the subjects existing immune system, inducing the subjects immune system to attack the tagged or target cells. In certain embodiments, there is provided the presentation of antigens from vaccines specifically on target cells of interest to elicit a recall immune response to these antigens that is available as a result of childhood or other vaccination. In certain embodiments, the present invention provides a targeted treatment for patients diagnosed with cancer.

[0025] In an embodiment, the present invention is a preventative treatment for

subjects who have been determined to be at risk of developing particular cancer. At risk patients may be determined through various methods known in the art or in the future including but not limited to genetic predispositions and hereditary traits. In an

embodiment the treatment is administered as a primary treatment or in conjunction with other treatments well known in the art.

[0026] In an embodiment, the disease target cells can be administered a factor, for example but not limited to a protein or variant of a protein, which is not present in healthy cells through restricted delivery to a specific tissue. [0027] In an embodiment, the target cells have a mutation not present in healthy cells that results in expression of factor, for example but not limited to a protein or variant of a protein, which is not present in healthy cells. In an embodiment, the expression of a factor that is unique to or predominantly specific to the disease cell enables expression of the antigen from a gene construct. In specific embodiments of the present invention, antigens are specifically expressed in target cells through administration of a gene construct encoding an antigen wherein expression or presentation of the antigen requires a factor (e.g., protein, gene, S P, transcription factor) selectively expressed in the target cells. For example, the gene construct contains the antigen with a promoter driven only by a factor selectively expressed in the target cells (e.g., a cancer cell-specific transcription factor).

[0028] In other embodiments, the expression of transformed viral genes in target cells enables the selective expression of proteins or peptides in these cells. A gene construct containing an antigen with a promoter driven by factors (e.g., proteins, peptides) expressed only in the virally -transformed cells, provides for specific expression of the antigen only in the target cell and therefore provides labeling of the target cells (e.g., a cancer cell) with the antigen. This results in activation of pre-existing memory immune responses against the antigen providing a targeted immune response against the target cells to treat the cancer. In certain embodiments, the methods of the present invention can be used to target pre-, active and metastatic cancerous cells.

[0029] In certain embodiments, the expression of transformed viral genes in

cancerous cells enables the selective synthesis of proteins or peptides in these cells that are necessary for expression of the antigen from the gene construct. In such embodiments, the method involves administration of a gene construct containing the antigen driven by a viral transformed promoter that requires transformed viral genes found in the cancerous cell for expression of the antigen.

[0030] In certain embodiments, specific utility of peptide antigens disclosed herein in cancers of low mutational burden or that are not sensitive to immune-based therapies such as, but not limited to, treatment with checkpoint inhibitors or CAR-T is contemplated. Expression of peptide antigens disclosed herein in combination with other immune-based therapies in such cancers represents a novel utility to make these cancers immune sensitive. Specifically, delivery of peptide antigens disclosed herein to cancers with low potential for neoantigen/epitope development will promote the immunogenic potential of said cancer. Thereby, administration of peptide antigens herein in combination with any of the delivery platforms described herein will make said cancer reactive to other immune therapies such as checkpoint inhibitors and CAR-Ts.

[0031] In different embodiments, the antigen to be selectively expressed and

presented by the target cells is an antigen from a vaccine including but not limited to childhood vaccines, e.g., chickenpox, measles, mumps, rubella, and polio. In certain embodiments, the antigen to be selectively expressed and presented by the target cells is a subsequence, homologue, variant or derivative of an antigen from a vaccine.

[0032] Towards this end, the present inventors have identified peptides derived from vaccine strains of viruses used in live-attenuated vaccines and inactivated vaccine administered during child- and adult- hood including chickenpox, measles, mumps, rubella, and polio that are broadly bound by HLA class I and class II molecules represented in humans from diverse ethnic, racial, and geographic backgrounds that can be used to recall memory T-cell responses.

[0033] The herein described approach allows expression of peptides derived from chickenpox, measles, mumps, rubella and polio for which common childhood vaccines have been administered for the past five decades in target cells to allow targeting of memory immune responses from these common vaccines. This approach is novel as it leverages existing, non-self memory immune responses to target T-cell responses against specific target cells including cancerous, transformed pre-cancerous cells, and metastasis as well as viral, parasitic and bacterial transformed cells.

[0034] In an embodiment, the compositions that comprise one or more peptides listed in Table 1, or a subsequence, homologue, variant or derivative thereof, are directly administered to the cancer tissue of the patient. In an embodiment, the composition can be administered by for example but not limited to viral vectors, micro- or nano- particles, direct injection, lipid particles, exosomes, gene, and/or adjuvanted delivery methods. In some embodiments, a composition described herein is administered by direct tissue injection, intratumoral injection, intravenous injection, intraperitoneal injection, subcutaneous injection, intramuscular injection, intravesivular injection or intrathecal injection.

[0035] In some embodiments, a subject is vaccinated prior to, concurrently with, or after the administering of (b). In certain embodiments, a vaccination is a booster vaccination. In some embodiments, the booster vaccination comprises at least one peptide listed in Tables 1. In some embodiments, the booster vaccination is a booster vaccination against chickenpox, measles, mumps, rubella, or polio.

[0036] In some embodiments, an anti-cancer therapy comprises administering

combinations of one or more small molecules, immune checkpoint inhibitors optionally selected from IDO/TDO inhibitors, and epigenetic regulators such as HDAC inhibitors. In some embodiments, an anti-cancer therapy comprises administering, alone or in combination, one or more cancer vaccines optionally based on cancer-associated tumor antigens, or neo-antigens.

[0037] In some embodiments, the one or more of the one or more peptide antigens are linked to a targeting antibody, antibody fragment or nanobody that is internalized by the target cell.

[0038] In some embodiments, a pre-existing T-cell memory is measured prior to the administering of (b). In certain embodiments, such measurement of pre-existing T cell memory can be done to identify subjects for treatment or to determine appropriate treatment for a subject (e.g. companion diagnostic).

[0039] In some embodiments, a few days to weeks prior to the administering of (b), the method comprises boosting immune memory in the subject by administering a vaccines or antigen that stimulates a recall immune response against the one or more peptide antigens.

[0040] In some aspects presented herein is a diagnostic tool for measuring immune response to a vaccine or recall immunity to a target cell comprising measuring an immune response to one or more peptides listed Table 1. In some embodiments, the measurement of recall immunity is prior to administration of a peptide listed in any of Table 1. In some embodiments, the measurement of recall immunity is prior to administration of a vector configured to expresses at least one peptide listed in any of Table 1.

[0041] In some embodiments, a recall and targeting of a pre-existing immune

responses (CD8/CD4) from childhood vaccines leads to tumor cell killing and optionally a subsequent 'abscopal' effect with systemic, cancer-specific immune responses.

[0042] In some embodiments, the one or more peptide antigens comprise full antigens or complete proteins derived from the pathogens.

[0043] In some aspects of a method herein, a subject is vaccinated prior to,

concurrently with, or after the administering of a vector or peptide of (b). In some embodiments, the vaccination is a booster vaccination. In certain embodiments, the booster vaccination comprises at least one peptide listed in Table 1. In certain

embodiments, the booster vaccination is a booster vaccination against chickenpox, measles, mumps, rubella, or polio.

DETAILED DESCRIPTION

Definitions

[0044] An "associated symptom, disease or disorder" as used herein refers to a symptom, disease or disorder that develops in conjunction with, following or as a result of a disease state {e.g., cancer). This includes acute and chronic diseases or disorders, short and long term disease and disorders, as well as related symptoms thereof.

[0045] The terms "subject," "patient," "individual," etc. are not intended to be

limiting and can be generally interchanged. That is, an individual described as a "patient" does not necessarily have a given disease, but may be merely seeking medical advice. In some embodiments, a subject is a mammal. Non-limiting examples of mammals include humans, non-human primates {e.g., apes, gibbons, chimpanzees, orangutans, monkeys, macaques, and the like), domestic animals (e.g., dogs and cats), farm animals (e.g., horses, cows, goats, sheep, pigs) and experimental animals (e.g., mouse, rat, rabbit, guinea pig). In certain embodiments a subject is a non-human mammal. In certain embodiments, a subject is a rodent (e.g., a rat or mouse). In some embodiments, a subject is a human.

[0046] The term "diagnosis" refers to a relative probability that a disease or condition (e.g. cancer) is present in the subject. In some instances, as will be appreciated by any one of skill in the field of medicine, a diagnosis may not be absolute or definite.

[0047] The terms "virus", "bacteria", "oncovirus", "cancer virus", "tumor virus" are intended to encompass a class of triggers that are associated with the development of or are the cause of a cancer, either currently known or yet to be confirmed or discovered. In some embodiments, the cause can be related to the insertion of viral or bacterial DNA or RNA into the genome of the target cell.

[0048] "Vaccination regimes" means vaccines, for example but not limited to MMR, oral polio vaccine, injectable polio vaccine, and chicken pox including those administered during childhood or adulthood.

[0049] As used herein, "recall response," "adaptive immune response",

"recall immune response," "memory response," "memory immune response" and grammatical variations thereof means an immune response to an antigen to which a subject has previously been exposed. A recall or memory response is therefore an immune response subsequent to the initial antigen exposure and immune response. For example, a recall response may occur following exposure of the subject to the antigen for a second (secondary), third (tertiary), fourth, fifth, sixth, seventh, eighth, ninth, tenth, or any subsequent antigen exposure.

[0050] A recall or memory response is distinguished from a primary response to an antigen; a primary response is an immune response that occurs when a subject is exposed to an antigen for the first time. In a primary response, naive B and T cells become activated, develop higher specificity and affinity, expand, and develop memory cells. In contrast, recall immune responses are believed to be attributed to reactivation of long- lived, antigen-primed B and T lymphocytes that arise from differentiated B and T cells in a quiescent state. Thus, a "recall response" is an immune response in which antigen- primed cytotoxic T cell, Thl, Th2, and/or B cells participate.

[0051] As used herein a "target cell", "target cells" in singular or plural, or grammatical variations thereof, refer to cells, which are affected by a disease or disorder, contribute to a disease or disorder, predisposed to transform into a disease or disorder and/or are targets of treatment. Target cells are distinguished from healthy or non-disease cells in that healthy or non-disease cells have normal function or are not desired targets of treatment. Non-limiting examples of target cells comprise cells, tissue or derivatives thereof from cancer or any other desired targeted cells subset.

[0052] Target cells may include cancer cells that have been transformed by a virus or bacteria, including but not limited to a Burkitt's lymphoma cancer cell, nasopharyngeal cancer cell, Hodgkin lymphoma cancer cell and stomach cancer cell (Epstein Barr Virus), Kaposi sarcoma cancer cell (human herpes vims 8); cervical cancer cell, penis cancer cell, anus cancer cell, vagina cancer cell, vulva cancer cell, throat and mouth cancer cell (human papillomavirus), liver cancer ceil (hepatitis B and C viruses), breast cancer cell or gliobastoma multiform ceil (human cytomegalovirus), T cell leukemia cell and lymphoma cell (Human T-lymphotrophic virus 1), mesothelioma cell, brain cancer cell, bone cancer cell and lymphomas (Simian vims 40), stomach cancer cells (Helicobacter pylori and merkel cell cancer cell (Merkel cell poSyomavirus)

[0053] In some embodiments, a target cell is a cancer cell or neoplastic cell. In certain embodiments, a target cell is a metastatic cancerous cell. Non-limiting examples of a cancer cell or neoplastic cell include a carcinoma, sarcoma, neuroblastoma, cervical cancer cell, hepatocellular cancer cell, mesothelioma, glioblastoma, myeloma, lymphoma, neoplastic lymphocyte, adenoma, adenocarcinoma, glioma, glioblastoma, retinoblastoma, astrocytoma, oligodendrocytoma, meningioma, melanoma, lymphosarcoma, liposarcoma, osteosarcoma, chondrosarcoma, leiomyosarcoma, rhabdomyosarcoma or fibrosarcoma.

[0054] In some embodiments, a target cell is a cell that is or has been infected with a pathogen. In certain embodiments, a target cell is a cell that is or has been infected with a vims, bacteria, parasite or protozoa. [0055] A pathogen can be a mammalian pathogen. In some embodiments a pathogen is a human pathogen. A pathogen can be a virus, bacteria, parasite or protozoa. Non- limiting examples of a pathogen include a virus of the order Flaviviridae, Retroviridae, Orthomyxoviridae, Arenaviridae, or Mononegavirales, a virus of the family Togaviridae, Reoviridae, picornaviridae, herpesviridae or Bunyaviridae. In certain embodiments a virus is a human papillomavirus. In certain embodiments, a virus is a hepatitis B or hepatitis C virus. In some embodiments, a virus is a Merkel cell polyomavirus.

[0056] As used herein "package" and "agent" are used synonymously and refer to the compositions of the invention that are administered to a subject or patient as part of a treatment described herein.

[0057] "Delivery mechanisms" refer to mechanisms (chemical, biological, physical and otherwise) that are utilized to introduce a package into the patient's system and cells. The present invention is not limited to the delivery mechanisms disclosed herein and one skilled in the art would appreciate that other mechanisms known in the art, as a whole, in part and in combination, can be used to deliver the packages to the target and desired cells.

[0058] As used herein, the terms "treatment", "treat" and "prevent" may refer to any delay in onset, reduction in the frequency or severity of symptoms, amelioration of symptoms, improvement in patient comfort or function, decrease in the occurrence of a given condition or disease or condition or disease symptoms in a patient, decrease in severity of the condition or disease state etc. The effect of treatment can be compared to an individual or pool of individuals not receiving a given treatment, or to the same patient prior to, or after cessation of, treatment. As indicated above, treatment may be complete (no detectable symptoms) or partial, such that fewer symptoms are observed than would likely occur absent treatment.

[0059] As used herein "antigen" refers to any protein, peptide, biological component, molecule or compound that induces an immune response. The term "epitope" refers to the specific region of the antigen that elicits the immune response. [0060] The terms "peptide" and "protein" refers to polymers of amino acid residues. The terms include amino acid polymers in which one or more amino acid residue is an artificial chemical mimetic of a corresponding naturally occurring amino acid, as well as to naturally occurring amino acid polymers and non-naturally occurring amino acid polymer. In certain embodiments, a peptide or protein described herein includes an epitope.

[0061] As used herein "variant" and grammatical variations thereof, refers to a

protein or peptide that deviates from a reference protein or peptide sequence. Modified and variant proteins or peptides may therefore have greater or less activity or function than a reference protein or peptide but at least retain partial activity or function of the reference protein or peptide.

[0062] "Conservatively modified variants" applies to both amino acid and nucleic acid sequences. With respect to particular nucleic acid sequences, conservatively modified variants refers to those nucleic acids which encode identical or essentially identical amino acid sequences, or where the nucleic acid does not encode an amino acid sequence, to essentially identical sequences. Because of the degeneracy of the genetic code, a large number of functionally identical nucleic acids encode any given protein. For instance, the codons GCA, GCC, GCG and GCU all encode the amino acid alanine. Thus, at every position where an alanine is specified by a codon, the codon can be altered to any of the corresponding codons described without altering the encoded polypeptide. Such nucleic acid variations are "silent variations," which are one species of conservatively modified variations. Every nucleic acid sequence herein, which encodes a polypeptide, also describes every possible silent variation of the nucleic acid. One of skill will recognize that each codon in a nucleic acid (except AUG, which is ordinarily the only codon for methionine, and TGG, which is ordinarily the only codon for tryptophan) can be modified to yield a functionally identical molecule. Accordingly, each silent variation of a nucleic acid, which encodes a polypeptide, is implicit in each described sequence with respect to the expression product, but not with respect to actual probe sequences.

[0063] As to amino acid sequences, one of skill will recognize that individual

substitutions, deletions or additions to a nucleic acid, peptide, polypeptide, or protein sequence which alters, adds or deletes a single amino acid or a small percentage of amino acids in the encoded sequence is a "conservatively modified variant" where the alteration results in the substitution of an amino acid with a chemically similar amino acid.

Conservative substitution tables providing functionally similar amino acids are well known in the art. Such conservatively modified variants are in addition to and do not exclude polymorphic variants, interspecies homologs, and alleles of the invention.

[0064] The following eight groups each contain amino acids that are conservative substitutions for one another: 1) Alanine (A), Glycine (G); 2) Aspartic acid (D), Glutamic acid (E); 3) Asparagine (N), Glutamine (Q); 4) Arginine (R), Lysine (K); 5) Isoleucine (I), Leucine (L), Methionine (M), Valine (V); 6) Phenylalanine (F), Tyrosine (Y), Tryptophan (W); 7) Serine (S), Threonine (T); and 8) Cysteine (C), Methionine (M) (see, e.g., Creighton, Proteins (1984)).

[0065] A "label" or a "detectable moiety" is a composition detectable by

spectroscopic, photochemical, biochemical, immunochemical, chemical, or other physical means. For example, useful labels include 32P, fluorescent dyes, electron-dense reagents, enzymes (e.g., as commonly used in an ELISA), biotin, digoxigenin, or haptens and proteins or other entities, which can be made detectable, e.g., by incorporating a radiolabel into a peptide or antibody specifically reactive with a target peptide. Any method known in the art for conjugating an antibody to the label may be employed, e.g., using methods described in Hermanson, Bioconjugate Techniques 1996, Academic Press, Inc., San Diego.

[0066] The term "recombinant" when used with reference, e.g., to a cell, or nucleic acid, protein, or vector, indicates that the cell, nucleic acid, protein or vector, has been modified by the introduction of a heterologous nucleic acid or protein or the alteration of a native nucleic acid or protein, or that the cell is derived from a cell so modified. Thus, for example, recombinant cells express genes that are not found within the native (non- recombinant) form of the cell or express native genes that are otherwise abnormally expressed, under expressed or not expressed at all.

[0067] The term "heterologous" when used with reference to portions of a nucleic acid indicates that the nucleic acid comprises two or more subsequences that are not found in the same relationship to each other in nature. For instance, the nucleic acid is typically recombinantly produced, having two or more sequences from unrelated genes arranged to make a new functional nucleic acid, e.g., a promoter from one source and a coding region from another source. Similarly, a heterologous protein indicates that the protein comprises two or more subsequences that are not found in the same relationship to each other in nature (e.g., a fusion protein).

[0068] As used herein, the terms "treatment", "treat" and "prevent" may refer to any delay in onset, reduction in the frequency or severity of symptoms, amelioration of symptoms, improvement in patient comfort or function, decrease in the occurrence of a given condition or disease or condition or disease symptoms in a patient, decrease in severity of the condition or disease state etc. The effect of treatment can be compared to an individual or pool of individuals not receiving a given treatment, or to the same patient prior to, or after cessation of, treatment. As indicated above, treatment may be complete (no detectable symptoms) or partial, such that fewer symptoms are observed than would likely occur absent treatment.

[0069] An "agent" as used herein refers to any molecule (e.g., antibody, nucleic acid, synthetic chemical, small chemical molecule, ligand mimetic) that can be administered to a subject. An agent that modulates an immune response is a molecule (e.g., antibody, nucleic acid, synthetic chemical, small chemical molecule) that when administered to a subject modulates an immune response in the subject. In certain embodiments, the agent modulates, inhibits, blocks, decreases, increases, enhances, promotes or elicits an acute or chronic immune response. In some embodiments, the agent modulates stimulation, activation proliferation, number or activity of immune proteins or cells (e.g., T cells, B cells, macrophages, monocytes, dendritic cells, cytokines). In certain embodiments, the agent modulates an innate immune response. In certain embodiments, the agent modulates a recall immune response. In particular embodiments, the agent modulates an immune response to one or more of the peptides listed in Table 1, or a subsequence, homologue, variant or derivative thereof. In particular aspects of the methods described herein an agent administered to a subject to treat cancer when administered to a subject in a therapeutically effective dose or amount. In some embodiments, an agent is an agent that binds one or more of the proteins listed in Table 1, or a subsequence, homologue, variant or derivative thereof.

[0070] In some embodiments, the agent binds one or more of the proteins listed in

Table 1, or a subsequence, homologue, variant or derivative thereof. In some

embodiments, the agent binds the complex of an immune cell or immune protein bound to one or more of the proteins listed in Table 1, or a subsequence, homologue, variant or derivative thereof.

[0071] Thus in particular embodiments, the agent modulates the activity or expression of one or more type of immune cell or protein (e.g., T cells, B cells, macrophages, monocytes, dendritic cells, cytokines) or a combination thereof. In some embodiments, the agent modulates the stimulation of T cells, activation of T cells, proliferation of T cells, number of T cells or activity of T cells, or a combination thereof. In some embodiments, the agent modulates the stimulation of B cells, activation of B cells, proliferation of B cells, number of B cells or activity of B cells, or a combination thereof. In some embodiments, the agent modulates stimulation, activation, proliferation, number or activity, or a combination thereof, of B cells generating antibodies (e.g., antibodies to one or more of the proteins listed in Table 1, or a subsequence, homologue, variant or derivative thereof).

[0072] In some embodiments, the agent modulates production or activity of

cytokines, immune activators, chemokines, growth factors and T F family members (e.g., AREG, Granzyme, Histamine, IFNct/β, IFNy, IL12, IL15, IL16, IL17a-f, Π.1 β, 112, IL21, IL22, IL23, IL25, IL27, GM-CSF, IL33, IL4, IL5, IL6, IL7, IL8, IL9, LFA-1, LIF, lymphotoxin, Mac-1, MCP-1, ΜΙΡΙα, Perforin, TGF-β, TNF a, VLA-4, CCL1, CCL1 1, CLL17, CCL1, CCL20, CCL22, CCL3, CCL4, CCL5, CXCL10, CXCL13, CXCL8, RANTES, CXCL12, G-CSF, M-CSF, VEGF, PDGF, 4-1BB, APRIL, BAFF, CD27, CD30, CD30L, CD70, DR3, DR4, DR5, FAS, FASL, GITR, HVEM, LIGHT, LTB, OX40, Ox40L, TACI, TRAIL, TWEAK, IL1 1, IL14 or IL10).

[0073] In some embodiments, the agent modulates activity or expression of immune cells or proteins involved in an immune response to one or more of the proteins listed in Table 1, or a subsequence, homologue, variant or derivative thereof. In certain

embodiments, the immune response is an innate immune response. In other embodiments, the immune response is a recall immune response. In particular embodiments, the agent modulates stimulation of T cells, activation of T cells, proliferation of T cells, number of T cells or activity of T cells, or a combination thereof, wherein the T cells are specific for one or more of the proteins listed in Table 1, or a subsequence, homologue, variant or derivative thereof. In particular embodiments, the agent modulates stimulation of B cells, activation of B cells, proliferation of B cells, number of B cells or activity of B cells, or a combination thereof, wherein the B cells are specific for one or more of the proteins listed in Table 1, or a subsequence, homologue, variant or derivative thereof.

[0074] Methods of treatment

[0075] Provided herein are methods of treating cancer in patients. The method involves selectively expressing in the target cells (e.g., cancer cells, viral, bacterial, parasite or protozoa infected cells) an antigen that the subject has previously developed immunity against. In particular embodiments, the method involves selectively expressing in target cells an antigen from a vaccine that the subject has previously received resulting in a recall immune response specific to the target cell. In particular embodiment, the antigen is from a vaccine the subject received in childhood including but not limited to one or more of the vaccines for chickenpox, measles, mumps, rubella, and polio.

[0076] In a preferred embodiment, the expression of particular antigens that are non- self immunogenic peptide antigens (e.g., proteins or epitopes) results in a signature labeling of the target cells with non-self immunogenic peptide antigens. The signature labeling is providing a means for the target cells to be singled out and differentiated from healthy ceils that are not expressing the particular antigens. In an embodiment, the expression of non-self immunogenic peptide antigens elicits a memory immune response against the target ceils that are expressing the particular antigens. In a preferred embodiment, memory T cells, e.g., CDS and/or CD4 T cells, specific to the non-self immunogenic peptides are reactivated.

[0077] In particular embodiments, the treatment comprises an antigen from a vaccine that is administered to a patient who has previously developed immunity against the antigen, resulting for example from childhood vaccination regimes, where the vaccine was effective in developing immunity against the disease for which the vaccine was designed. In particular embodiments, the patient has been vaccinated against a disease and has developed immunity to these infections such that immunity can be detected, boosted and measured. In certain, embodiment, the patient received vaccination against the disease during childhood. In other embodiments, the patient has been previously infected with a virus, bacteria, parasite or protozoa expressing the antigen and has developed immunity to the antigen due to this prior infection. In some embodiments, a subject has been previously vaccinated against a pathogen. In a preferred embodiment the developed immunity is against chickenpox, measles, mumps, rubella and polio.

[0078] In a preferred embodiment, the subject' s immune system is able to recall an immune response developed from a previous vaccination regime or infections. In some embodiments, the subject may be administered a booster vaccination to prime immune memory (e.g., increase antibody titers, memory T cells) prior to administration of a method or composition of the present invention. In an embodiment, immunity may be induced using other vaccination methods other than childhood vaccines.

[0079] In particular embodiments, the antigen is selectively expressed in the target cells through administration of a gene construct encoding an antigen wherein expression or presentation of the antigen requires a factor (e.g., protein, gene, S P, transcription factor) selectively expressed in the target cells. For example, the gene construct contains the antigen with a promoter driven only by a factor selectively expressed in the target cells (e.g., a cancer cell-specific transcription factor). In certain embodiments, this specific expression of the necessary factor in the target cells is a result of the target cells being infected by a virus, bacteria, parasite or protozoa such that there is expression of transformed viral genes or bacterial, parasitic or protozoa genes present in the target cells which encode for the necessary factors to express the antigen from the gene construct.

[0080] In certain embodiments, the gene construct comprises the antigen with a

promoter driven only by a factor selectively expressed in the target cells (e.g., a cancer cell-specific or infected cell-specific transcription factor). Thus, in certain embodiments, a gene construct that contains a promoter driven only by a factor expressed by target cells that have been infected with a particular virus, bacteria, protozoa or parasite is

administered to the subject, enters or is ingested by the subject cells and the viral, bacterial, parasitic or protozoa genes in the target cells enables the selective expression of proteins or peptides in these cells that are needed for expression of the antigen from the gene construct. Only the target cells that contain the viral, bacterial, parasitic or protozoa genes will express the antigen resulting in a recall immune response specific to the target cells.

[0081] In other embodiments, the antigen is specifically expressed in target cells by- targeted delivery of the antigen to the target cells. Non-limiting examples of methods for targeted delivery of the antigen to the target cells including administration by direct intratumoral injection, micro- or nano-particles, liposome, PEGylation, lipofectamine, adenovirus, lentivirus, vaccinia virus or other viral gene vector, and/or CRISPR/CAS9.

[0082] In an embodiment, the present invention comprise administering an optimized package comprising one or more antigens (e.g., peptide antigens). Non-limiting examples of peptide antigens include a peptide selected from Table 1, or a subsequence,

homologue, variant or derivative of a peptide listed in Table 1. In particular

embodiments, the optimized package included one or more epitopes from antigen against which the subject has immune memory, e.g., epitopes from childhood vaccines. In specific embodiments, the optimized package compri ses one or more CD4 and/or CDS T- cell epitopes, for example, one or more of the epitopes listed in Table 1, or a subsequence, homologue, variant or derivative thereof. In certain embodiments, the optimized package contains epitopes selected for their broad recognition by HLA class I molecules of subjects from diverse ethnic and geographical backgrounds.

[0083] In an embodiment, the method includes administering the antigen and epitopes in combination with factors that induce an increase of epitope presentation by MHC molecules (e.g., TAP expression; antennapedia homeodomain peptide) and/or activation and recruitment of APCs (i.e. GM-CSF, anti-immune suppressive agents, or chemokines). The increased expression accelerates the T-cell response and ability to clear the target cells. In an embodiment, the present invention provides a gene construct encoding the antigen and genes for increased expression of cytokines, immune activators, chemokines, growth factors and TNF family members to amplify the inflammatory T cell response by the recalled immune system. In different embodiments, the gene constructs comprises genes for one or more of AREG, Granzyme, Histamine, IFNa/β, ΠΤΝΓγ, IL12, IL15, IL16, IL17a-f, ILlb, 112, IL21, IL22, IL23, IL25, IL27, GM-CSF, IL33, IL4, IL5, IL6, IL7, IL8, IL9, LFA-1, LIF, lymphotoxin, Mac-1, MCP-1, ΜΙΡΙα, Perforin, TGF-β, TNFa, VLA-4, CCL1, CCL1 1, CLL17, CCL1, CCL20, CCL22, CCL3, CCL4, CCL5, CXCL10, CXCL13, CXCL8, RANTES, CXCL12, G-CSF, M-CSF, VEGF, PDGF, 4-1BB, APRIL, BAFF, CD27, CD30, CD30L, CD70, DR3, DR4, DR5, FAS, FASL, GITR, HVEM, LIGHT, LTB, OX40, OX40L, TACI, TRAIL, TWEAK, IL1 1, IL14 and IL10. 84] In particular embodiments, the treatment is directed towards hematological and solid tumors and cancer, including but not limited to tumors and cancers involving or caused by viral, parasitic or bacterial infection that can be targeted by local administration or tissue-targeting agents, or cancers of low mutational burden where reduced efficacy is observed following other cancer immunotherapies. Non-limiting examples of cancers that may be treated by the present invention include a neoplasia derived from lung, thyroid, head or neck, nasopharynx, throat, nose, sinus, brain, spine, breast, adrenal gland, pituitary gland, thyroid, lymph, mouth, esophagus, stomach, duodenum, ileum, jejunum intestine, colon, rectum, uterus, urethra, ovary, cervix, endometrium, bladder, testicle, penis, prostate, kidney, pancreas, liver, bone, bone marrow, lymph, blood, muscle, and skin; a carcinoma, sarcoma, neuroblastoma, hepatocellular cancer, mesothelioma, glioblastoma, myeloma, lymphoma, myeloma, leukemia, adenoma, adenocarcinoma, glioma, glioblastoma, retinoblastoma, astrocytoma, oligodendrocytoma, meningioma, and a melanoma; a cervical cancer, breast cancer, liver cancer, pancreatic cancer, brain cancer, lung cancer, skin cancer, ovarian cancer, and a testicular cancer. In some embodiments, a cancer is an infection-induced cancer. Non-limiting examples of infection-induced cancers include a hepatocellular carcinoma, cervical cancer (human papilloniaviixis), head and neck squamous cell carcinoma (HNSCC), adult T-cell leukemia/lymphoma, liver cancer (hepatitis B and C viruses), Burkitt' s lymphoma and Kaposi sarcoma (Epstein-Barr virus), Merkel cell cancer (e.g., Merkel cell carcinoma) (Merkel cell polyomavirus), bladder cancer and gastric cancer. [0085] In some embodiments, a cancer comprises a low mutational burden, non- limiting examples of which include pilocytic astrocytoma, ALL, medulloblastoma, kidney chromophobe, thyroid, CLL, neuroblastoma, glioblastoma, and pancreatic cancer.

[0086] In some embodiments a method comprises administering a checkpoint blocker. In certain embodiments, a method comprises adoptive transfer of T-cells containing a chimeric antigen receptor (CAR).

Pharmaceutical compositions

[0087] In an embodiment, the present invention provides epitopes from childhood vaccines that can be administered in the methods described herein. Thus there is presently provided compositions comprising proteins and peptides comprising epitopes from childhood vaccines, including but not limited to chickenpox, measles, mumps, rubella, and polio. In certain embodiments, the protein or peptide comprises, consists or consists essentially of one or more of the amino acid sequences listed in Table 1, or a

subsequence, homologue, variant or derivative thereof.

[0088] In particular embodiments, the present invention provides a composition

comprising combinations of epitopes from childhood vaccines. Thus, in particular embodiments, the present invention provides combinations of one or more proteins or peptides each comprising, consisting or consisting essentially of a different amino acid sequence listed in Table 1, or a subsequence, homologue, variant or derivative thereof.

[0089] In other embodiments, the present invention provides a composition

comprising a gene construct encoding one or more epitopes from childhood vaccines. Thus in certain embodiments, the present invention provides a gene construct encoding one or more of the amino acid sequences listed in Table 1, or a subsequence, homologue, variant or derivative thereof. In some embodiments a composition comprises a viral construct configured to express one or more of the amino acid sequences listed in Table 1, or a subsequence, homologue, variant or derivative thereof. In certain embodiments a composition comprises agents to improve peptide:HLA expression (e.g., TAP;

antennapedia homeodomain peptide). In certain embodiments a composition comprises agents to improve immune infiltration. In certain embodiments a composition comprises agents to modulate checkpoint inhibition. In certain embodiments a composition comprises T cells that are adoptively transferred containing CAR specific to one or more of the peptides listed in Table 1.

[0090] In different embodiments of the present invention, epitopes are selected for their broad recognition by HLA class I or class II molecules of subjects from diverse ethnic, racial and geographical backgrounds.

[0091] In a further embodiment, the present invention provides a uniquely optimized package and appropriate delivery system for introducing the treatment into the subject. Thus, in a preferred embodiment the composition of the present invention comprises viral, bacterial, parasitic, protozoa or cancer specific transformed promoter, epitopes, proteins, factors that increase epitope expression in MHC pockets and genes that increase cytokine expression. In particular embodiments, one or more epitopes are selected from the peptides in Table 1 to 10, or a subsequence, homologue, variant or derivative thereof.

[0092] In particular embodiments, the composition comprises CD4 and/or CD8 T-cell epitopes from the mumps vaccine. In particular embodiments, the composition comprises T-cell (e.g., CD8 and/or CD4 T cells) epitopes from the measles vaccine. In particular embodiments, the composition comprises CD4 and/or CD8 T-cell epitopes from the rubella vaccine. In particular embodiments, the composition comprises CD4 and/or CD8 T-cell epitopes from the polio vaccine. In particular embodiments, the composition comprises CD4 and/or CD8 T-cell epitopes from the chicken pox/varicella vaccine, comprising one or more or a combination of the peptides listed in Table 1.

[0093] In particular embodiments, the composition comprises proteins, peptides or epitopes from two or more different vaccines (e.g., measles, mumps, rubella, polio or chicken pox vaccine). In different embodiments, the composition comprises proteins, peptides or epitopes from two or more, three or more, four or more, or five or more different vaccines. In different embodiments, the composition may contain the same number of proteins, peptides or epitopes from each of the two or more vaccines or may contain a different number of proteins, peptides or epitopes from each of the two or more vaccines. [0094] As each T-cell epitope binds only a subset of naturally occurring HLA class II molecules in the human population and this repertoire of HLA class II molecules varies from one person to another and from one ethnic population to another, in certain embodiments of the presentation invention, it is desirable to select a mix of several peptides covering different HLA class II molecules to generate an immune response in a broad segment of the population. Further, in other embodiments of the present invention, it is desirable to select peptides that elicit an immune response (e.g., T-cell response) in a significant fraction of patients with the disease, disorder or condition to be treated. Thus, in particular embodiments, it is desirable to select an epitope or combination of epitopes that have a HLA class II repertoire covering a high fraction of a worldwide population, and which also produce an immune response (e.g., T cell response) in a significant fraction of patients with the disease, disorder or condition to be treated.

[0095] As each T cell epitope binds only a subset of naturally occurring HLA class I molecules in the human population and this repertoire of HLA class I molecules varies from one person to another and from one ethnic population to another, in certain embodiments of the presentation invention, it is desirable to select a mix of several peptides covering different HLA class I molecules to generate an immune response in a broad segment of the population. Further, in other embodiments of the present invention, it is desirable to select peptides that elicit an immune response (e.g., T-cell response) in a significant fraction of patients with the disease, disorder or condition to be treated. Thus, in particular embodiments, it is desirable to select an epitope or combination of epitopes that have a HLA class I repertoire covering a high fraction of a worldwide population, and which also produce an immune response (e.g., T-cell response) in a significant fraction of patients with the disease, disorder or condition to be treated.

[0096] In particular embodiments, it is desirable for the methods or compositions of the present invention to include as few peptides as possible, but at the same time to be able to treat the majority of patients in a worldwide population with the same method or composition. Such a method or should contain a combination of peptides capable of binding to a HLA Class II and/or Class I repertoire covering a high fraction of a worldwide population, and the resulting peptide-HLA complexes should be recognized as epitopes (e.g., T cell epitopes) in the subject so as to induce an immune response.

[0097] In particular embodiments, the composition of the present invention further comprises cytokines, immune activators, chemokines, growth factors or T F family members or a gene for increased expression of cytokines, immune activators,

chemokines, growth factors or TNF family members to amplify the inflammatory T-cell response by the recalled immune system. In different embodiments, the composition comprises one or more of or genes for one or more of AREG, Granzyme, Histamine, IFNa/β, IFNy, IL12, IL15, IL16, IL17a-f, ILlb, 112, IL21, IL22, IL23, IL25, IL27, GM- CSF, IL33, IL4, IL5, IL6, IL7, IL8, IL9, LFA-1, LIF, lymphotoxin, Mac-1, MCP-1, ΜΙΡΙα, Perforin, TGF-β, TNFa, VLA-4, CCL1, CCL1 1, CLL17, CCL1, CCL20, CCL22, CCL3, CCL4, CCL5, CXCL10, CXCL13, CXCL8, RANTES, CXCL12, G-CSF, M-CSF, VEGF, PDGF, 4-lBB, APRIL, BAFF, CD27, CD30, CD30L, CD70, DR3, DR4, DR5, FAS, FASL, GITR, HVEM, LIGHT, LTB, OX40, Ox40L, TACI, TRAIL,

TWEAK, IL1 1, IL14 and IL10.

Delivery Methods

[0098] In an embodiment, particular compositions are delivered to the target disease cells via one or more delivery systems depending on the indication, disease state, severity, clinical utility and other relevant parameters that may impact the desired efficacy of delivery and expression of the T-cell epitopes and/or antigens. In a preferred embodiment, the delivery system is engineered to deliver the package to a specific cell subset of interest.

[0099] In particular embodiments, the composition is delivered to the target cell and other cells of interest using delivery methods comprising one or more but at least one of the methods from the group comprising: replicating or non-replicating viral vectors such as Adenovirus (AdV); Adeno-associated virus (AAV); Lentivirus; Vaccinia virus;

Oncolytic viruses; Respective disease causing live, attenuated, or inactivated virus;

Micro/nano particles; Adjuvant emulsified; Electroporation; Bacteriophage; Lipid particles (e.g., Lipofectamine); Exosomes; Mineral oil / Freund's adjuvant; Hyperglycosylation; Pegylation; Poly(lactic/gly colic) acid; Direct injection; Conjugation via cell penetrating peptides/proteins; Lysosomal targeting agents; Gene delivery (e.g., Crispr-Cas9, flox/LoxP). The one or more delivery methods can be used in combination, alone, and in combinations in part thereof. Parts of particular delivery methods may be combined to other delivery methods to form new delivery methods. Other delivery methods well known in the art can be utilized to delivery the composition to the target cells. In particular embodiments, one or more epitopes are selected from the peptides listed in Table 1, or a subsequence, homologue, variant or derivative thereof, are delivered to the target cell using the delivery methods disclosed herein.

[00100] A peptide's immunogenicity, more particularly one or more epitopes from the peptides listed in Table 1, or a subsequence, homologue, variant or derivative thereof, may be modified. In particular embodiments, the modifications to the peptides and/or antigens administered comprise one or more of the modifications from the group comprising: Oxidization; Reduction; Citrullination; Glycatation (including but not limited to: prenylation, myristylation, palmitolation); Nitration; Di-sulfide bonding (Cysteine); Transglutamination; Deamidation; Misfolding; Single amino acid substitutions; Genetic frameshift mutations. The modifications are not intended to be limiting by scope or category but rather an illustration of how the peptides may be constructed in the delivery mechanisms.

[00101] The exact formulation and route of administration for a composition for use according to the methods of the invention described herein can be chosen by the individual physician in view of the patient's condition. See e.g., Fingl et al. 1975, in "The Pharmacological Basis of Therapeutics," Ch. 1 p. 1; which is incorporated herein by reference in its entirety. Any suitable route of administration can be used for

administration of a composition or compound described herein. Non-limiting examples of routes of administration include topical or local (e.g., transdermally or cutaneously, (e.g., on the skin or epidermis), in or on the eye, intranasally, transmucosally, in the ear, inside the ear (e.g., behind the ear drum)), enteral (e.g., delivered through the

gastrointestinal tract, e.g., orally (e.g., as a tablet, capsule, granule, liquid, emulsification, lozenge, or combination thereof), sublingual, by gastric feeding tube, rectally, and the like), by parenteral administration (e.g., parenterally, e.g., intravenously, intra-arterially, intramuscularly, intraperitoneally, intradermally, subcutaneously, intracavity, intracranially, intraarticular, into a joint space, intracardiac (into the heart), intracavernous injection, intralesional (into a skin lesion), intraosseous infusion (into the bone marrow), intrathecal (into the spinal canal), intrauterine, intravaginal, intratumoral, intravesical , intravitreal), the like or combinations thereof.

[00102] In some embodiments, a composition herein is provided to a subject. A composition that is provided to a subject is often provided to a subject for self- administration or for administration to a subject by another (e.g., a non-medical professional). For example, a composition described herein can be provided as an instruction written by a medical practitioner that authorizes a patient to be provided a composition or treatment described herein (e.g., a prescription). In another example, a composition can be provided to a subject wherein the subject self-administers a composition orally, intravenously or by way of an inhaler, for example.

[00103] Compositions herein can be formulated to be compatible with a particular route of administration or use. Compositions for parenteral, intradermal, or subcutaneous administration can include a sterile diluent, such as water, saline solution, fixed oils, polyethylene glycols, glycerine, propylene glycol or other synthetic solvents. The preparation may contain one or more preservatives to prevent microorganism growth (e.g., antibacterial agents such as benzyl alcohol or methyl parabens; antioxidants such as ascorbic acid or sodium bisulfite; chelating agents such as EDTA; buffers such as acetates, citrates or phosphates and agents for the adjustment of tonicity such as sodium chloride or dextrose). In certain embodiments, a composition herein is substantially free of a chelator (e.g., a zinc chelator, e.g., EDTA or EGTA).

[00104] Compositions for injection include sterile aqueous solutions (where water soluble) or dispersions and sterile powders for the extemporaneous preparation of sterile injectable solutions or dispersion. For intravenous administration, suitable carriers include physiological saline, bacteriostatic water, Cremophor EL™ (BASF, Parsippany, NJ), hydroxypropyl-b- cyclodextrin or other cyclodextrin derivatives, phosphate buffered saline (PBS). The carrier can be a solvent or dispersion medium containing, for example, water, ethanol, polyol (e.g., glycerol, propylene glycol, and polyethylene glycol), and suitable mixtures thereof. Fluidity can be maintained, for example, by the use of a coating such as lecithin, or by the use of surfactants. Antibacterial and antifungal agents include, for example, parabens, chlorobutanol, phenol, ascorbic acid and thimerosal. Including an agent that delays absorption, for example, aluminum monostearate and gelatin can prolong absorption of injectable compositions. Polysorbate 20 and polysorbate 80 can be added into the formulation mixture, for example, up to 1%. Other non-limiting additives include histidine HC1, α,α-trehalose dehydrate, sucrose, lactose or mannitol.

[00105] Alternatively, one can administer compositions for use according to the methods of the invention in a local rather than systemic manner, for example, via direct application to the skin, mucous membrane or region of interest for treating, including using a depot or sustained release formulation.

[00106] In some embodiments, active ingredients (e.g., peptides or vectors) can be administered alone. In other embodiments, active ingredients can be administered in combination with one or more additional materials, for example, as two separate compositions or as a single composition where the additional material(s) is (are) mixed or formulated together with an active ingredient. For example, without being limited thereto, an active ingredient can be formulated with additional excipients, or additional active ingredients. In some aspects, when administered in the forms described herein the active ingredients can attain concentrations at a target tissue such as the nose, mucous membranes, the bronchi, the skin, etc. that cannot be attained by the usual intravascular administration of the active ingredients.

[00107] The pharmaceutical compositions can be manufactured by any suitable manner, including, e.g., by means of conventional mixing, dissolving, granulating, dragee-making, levigating, emulsifying, encapsulating, entrapping or tableting processes.

[00108] Pharmaceutical compositions for use in accordance with the invention thus can be formulated in any suitable manner using one or more physiologically acceptable carriers comprising excipients and auxiliaries, which facilitate processing of the active compounds into preparations which can be used pharmaceutically. Proper formulation can depend upon the route of administration chosen. In particular, any suitable formulation, ingredient, excipient, the like or combinations thereof as listed in "Remington's Pharmaceutical Sciences," Mack Publishing Co., Easton, PA, 18th edition, 1990, can be used with a composition described herein. The various materials listed herein, alone or in combination, can be incorporated into or used with the materials described in Remington's. Any suitable techniques, carriers, and excipients can be used, including those understood in the art; e.g., in Remington's Pharmaceutical Sciences, above. The pages in the attached Appendix from Remington's Pharmaceutical Sciences are incorporated herein by reference in their entirety, including without limitation for all of the types of formulations, methods of making, etc.

Formulations

[00109] In some embodiments, the composition may be formulated, for example, as a topical formulation. The topical formulation may include, for example, a formulation such as a gel formulation, a cream formulation, a lotion formulation, a paste formulation, an ointment formulation, an oil formulation, and a foam formulation. The composition further may include, for example, an absorption emollient.

[00110] In some embodiments, at least part of the affected area of the mammal is contacted with the composition on a daily basis, on an as-needed basis, or on a regular interval such as twice daily, three times daily, every other day, etc. The composition can be administered for a period of time ranging from a single as needed administration to administration for 1 day to multiple years, or any value there between, (e.g., 1 - 90 days, 1 - 60 days, 1 - 30 days). The dosages described herein can be daily dosages or the dosage of an individual administration, for example, even if multiple administrations occur (e.g., 2 sprays into a nostril).

[00111] Some embodiments relate to methods of treating or preventing cancer through administration of compositions described herein to the upper respiratory track/bronchi in a mammal in need thereof, for example, by contacting at least part of the upper respiratory tract/bronchi of a mammal with a therapeutically effective amount of a composition as described above or elsewhere herein. The composition can be, for example, formulated as an aerosol formulation, including formulated for use in a nebulizer or an inhaler. The composition further may include other pharmaceutically acceptable components such as a preservative.

[00112] Other embodiments relate to aerosol compositions that include, for example, a composition as described herein and an aerosolized pharmaceutically acceptable carrier solution or dry powder. The compositions may be formulated, for example, to be substantially absorbed by a bronchus. The compositions also may include, for example, one or more of dichlorodifluoromethane, trichlorofluoromethane,

dichlorotetrafluoroethane, carbon dioxide, and the like. The compositions can be formulated for use in a nebulizer or an inhaler, for example.

Pharmaceutical Carriers

[00113] The term "carrier" defines a chemical compound that facilitates the incorporation of a compound into cells or tissues. For example dimethyl sulfoxide (DMSO) is a commonly utilized carrier as it facilitates the uptake of many organic compounds into the cells or tissues of an organism. In some embodiments, a pharmaceutical carrier for a composition described herein can be selected from castor oil, ethylene glycol, monobutyl ether, diethylene glycol monoethyl ether, corn oil, dimethyl sulfoxide, ethylene glycol, isopropanol, soybean oil, glycerin, zinc oxide, titanium dioxide, glycerin, butylene glycol, cetyl alcohol, and sodium hyaluronate.

[00114] In certain embodiments comprising hydrophobic excipients, additives, or other hydrophobic components, a pharmaceutical carrier for certain of such hydrophobic compounds can be a co-solvent system comprising benzyl alcohol, a nonpolar surfactant, a water-miscible organic polymer, and an aqueous phase. A common co-solvent system used is the VPD co-solvent system, which is a solution of 3% w/v benzyl alcohol, 8% w/v of the nonpolar surfactant POLYSORBATE 80™, and 65% w/v polyethylene glycol 300, made up to volume in absolute ethanol. Naturally, the proportions of a co-solvent system can be varied considerably without destroying its solubility and toxicity characteristics. Furthermore, the identity of the co-solvent components can be varied: for example, other low-toxicity nonpolar surfactants can be used instead of POLYSORBATE 80™; the fraction size of polyethylene glycol can be varied; other biocompatible polymers can replace polyethylene glycol, e.g., polyvinyl pyrrolidone; and other sugars or polysaccharides can substitute for dextrose. [00115] Alternatively, other delivery systems for hydrophobic pharmaceutical compounds, excipients, or additives can be employed, if required. Liposomes and emulsions are well known examples of delivery vehicles or carriers for hydrophobic drugs and drug compositions. Certain organic solvents such as dimethyl sulfoxide also can be employed, although usually at the cost of greater toxicity. Additionally, the compounds can be delivered using a sustained-release system, such as semipermeable matrices of solid hydrophobic polymers containing the therapeutic agent. The pharmaceutical compositions described herein can be administered to a patient per se, or in pharmaceutical compositions where they are mixed with other active ingredients, as in combination therapy, or suitable carriers or excipient(s). The compounds and compositions can be formulated with salts or excipients, such as for example, sodium or meglumine. Techniques for formulation and administration of the compounds of the instant application can be found in "Remington's Pharmaceutical Sciences," Mack Publishing Co., Easton, PA, 18th edition, 1990.

[00116] Furthermore, the compounds and compositions used herein can preferably be stable over an extended period of time, for example on the order of months or years. Compositions described herein, in some embodiments, comprise a preservative. The preservative can comprise a quaternary ammonium compound, such as benzalkonium chloride, benzoxonium chloride, benzethonium chloride, cetrimide, sepazonium chloride, cetylpyridinium chloride, or domiphen bromide (BRADOSOL®). The preservative can comprise an alkyl-mercury salt of thiosalicylic acid, such as thiomersal, phenylmercuric nitrate, phenylmercuric acetate or phenylmercuric borate. The preservative can comprise a parabens, such as methylparaben or propylparaben. The preservative can comprise an alcohol, such as chlorobutanol, benzyl alcohol or phenyl ethyl alcohol. The preservative can comprise a biguanide derivative, such as chlorohexidine or polyhexamethylene biguanide. The preservative can comprise sodium perborate, imidazolidinyl urea, and/or sorbic acid. The preservative can comprise stabilized oxychloro complexes, such as known and commercially available under the trade name PURITE®). The preservative can comprise polyglycol-polyamine condensation resins, such as known and commercially available under the trade name POLYQUART® from Henkel KGaA. The preservative can comprise stabilized hydrogen peroxide generated from a source of hydrogen peroxide for providing an effective trace amount of resultant hydrogen peroxide, such as sodium perborate tetrahydrate. The preservative can be benzalkonium chloride.

[00117] The preservative can enable a composition to be used on multiple occasions.

The preservative can reduce the effects of one or more of acid exposure, base exposure, air exposure, heat, and light on the active ingredient. The compounds and compositions used herein can include any suitable buffers, such as for example, sodium citrate buffer and/or sequestering agents, such as edetate disodium sequestering agent. Ingredients, such as meglumine, may be added to adjust the pH of a composition or compound described herein. Compounds and compositions described herein may comprise sodium and/or iodine, such as organically bound iodine. Compositions and compounds used herein may be provided in a container in which the air is replaced by another substance, such as nitrogen.

Dosages and Products

[00118] Certain embodiments provide pharmaceutical compositions suitable for use in the technology, which include compositions where the active ingredients are contained in an amount effective to achieve its intended purpose. A "therapeutically effective amount" means an amount to prevent, treat, reduce the severity of, delay the onset of or inhibit a symptom of a cancer. The symptom can be a symptom already occurring or expected to occur. Determination of a therapeutically effective amount is well within the capability of those skilled in the art, especially in light of the detailed disclosure provided herein.

[00119] In other embodiments, a therapeutically effective amount can describe the amount necessary for a significant quantity of the composition to contact the desired region or tissue where prevention or treatment of a cancer is desired.

[00120] Compositions described herein can be administered at a suitable dose, e.g., at a suitable volume and concentration depending on the route of administration. Within certain embodiments of the invention, dosages of an administered composition, vector, factor, agent or peptide can be from 0.001 - 200 grams, or 0.001 - 50 grams, 0.001 - 10 grams, etc. In some aspects the amount can be, for example, from 0.001 - 0.1 grams, 0.1 - 5 grams, 5 - 10 grams, 10 - 15 grams, 15 - 20 grams, 20 - 25 grams, 25 - 30 grams, 30 - 35 grams, 35 - 40 grains, 40 - 45 grams, 45 - 50 grams and 50 - 200 grams. In some non- limiting aspects, a composition, vector, factor, agent or peptide can be provided in a concentration, for example, of 1 mg/kg to 5000 mg/kg, 50 mg/kg to 1000 mg/kg, 50 mg/kg to 500 mg/kg, 150 mg/kg to 350 mg/kg or 350 mg/kg to 1000 mg/kg. In certain embodiments a composition, vector, factor, agent or peptide described herein can be administered at a concentration of at least 50 mg/kg, at least 100 mg/kg, at least 150 mg/kg, at least 200 mg/kg, at least 150 mg/kg, at least 200 mg/kg, at least 250 mg/kg, at least 300 mg/kg, at least 350 mg/kg, at least 400 mg/kg, at least 450 mg/kg, or at least 500 mg/kg. In certain embodiments a composition, vector, factor, agent or peptide described herein can be administered at a concentration of about 100 mg/kg, about 150 mg/kg, about 200 mg/kg, about 150 mg/kg, about 200 mg/kg, about 250 mg/kg, about 300 mg/kg, about 350 mg/kg, about 400 mg/kg, about 450 mg/kg, or about 500 mg/kg. Volumes suitable for intravenous administration are well known. For example, 50 ml - 100 ml of a composition, vector, factor, agent or peptide at a working concentration of between about 200 mg/kg to about 350 mg/kg can be safely administered intravenously to an adult human subject.

[00121] In some embodiments, the amount delivered can be any suitable amount, for example, in order to contact the desired tissue in a therapeutically effective manner. In certain embodiments, the compositions can be delivered to the nose, and the amount delivered to each nostril can be from about 20 microliters to about 1500 microliters, 50 microliters to about 1000 microliters, or 50 microliters to about 500 microliters. In some embodiments, composition described herein can be delivered to the nose in a volume of about 50, 100, 200, 300, 400 or 500 microliters for example.

[00122] The compositions can, if desired, be presented in a pack or dispenser device, which can contain one or more unit dosage forms containing the active ingredient. The pack can for example comprise metal or plastic foil, such as a blister pack. The pack or dispenser device can be accompanied by instructions for administration. The pack or dispenser can also be accompanied with a notice associated with the container in form prescribed by a governmental agency regulating the manufacture, use, or sale of pharmaceuticals, which notice is reflective of approval by the agency of the form of the drug for human or veterinary administration. Such notice, for example, can be the labeling approved by the U.S. Food and Drug Administration for prescription drugs, or the approved product insert. Compositions comprising a compound of the invention formulated in a compatible pharmaceutical carrier can also be prepared, placed in an appropriate container, and labeled for treatment of an indicated condition.

Kits

[00123] In some embodiments the compositions, formulations, combination products and materials described herein can be included as part of kits, which kits can include one or more of the compositions, vectors, factors, agents or peptides described herein, formulations of the same, combination drugs and products and other materials described herein. In some embodiments the products, compositions, kits, formulations, etc. can come in an amount, package, product format with enough medication to treat a patient for 1 day to 1 year, 1 day to 180 days, 1 day to 120 days, 1 day to 90 days, 1 day to 60 days, 1 day to 30 days, or any day or number of days there between.

[00124] The invention provides kits including a composition, vector, factor, agent or peptide of the invention, combination compositions and pharmaceutical formulations thereof, packaged into suitable packaging material. A kit optionally includes a label or packaging insert including a description of the components or instructions for use in vitro, in vivo, or ex vivo, of the components therein. Exemplary instructions include instructions for a method, treatment protocol or therapeutic regimen.

[00125] A kit can contain a collection of such components, e.g., two or more conjugates alone, or in combination with another therapeutically useful composition (e.g., an anti-proliferative or immune-enhancing drug). The term "packaging material" refers to a physical structure housing the components of the kit. The packaging material can maintain the components sterilely, and can be made of material commonly used for such purposes (e.g., paper, corrugated fiber, glass, plastic, foil, ampules, vials, tubes, etc.).

[00126] Kits can include labels or inserts. Labels or inserts include "printed matter," e.g., paper or cardboard, or separate or affixed to a component, a kit or packing material (e.g., a box), or attached to an ampule, tube or vial containing a kit component. Labels or inserts can additionally include a computer readable medium, optical disk such as CD- or DVD-ROM/RAM, DVD, MP3, magnetic tape, or an electrical storage media such as RAM and ROM or hybrids of these such as magnetic/optical storage media, FLASH media or memory type cards.

[00127] Labels or inserts can include identifying information of one or more components therein, dose amounts, clinical pharmacology of the active ingredient(s) including mechanism of action, pharmacokinetics (PK) and pharmacodynamics (PD). Labels or inserts can include information identifying manufacturer information, lot numbers, manufacturer location and date.

[00128] Labels or inserts can include information on a condition, disorder, disease or symptom for which a kit component may be used. Labels or inserts can include instructions for the clinician or for a subject for using one or more of the kit components in a method, treatment protocol or therapeutic regimen. Instructions can include dosage amounts, frequency or duration, and instructions for practicing any of the methods, treatment protocols or therapeutic regimes set forth herein. Kits of the invention therefore can additionally include labels or instructions for practicing any of the methods and uses of the invention described herein.

[00129] Labels or inserts can include information on any benefit that a component may provide, such as a prophylactic or therapeutic benefit. Labels or inserts can include information on potential adverse side effects, such as warnings to the subject or clinician regarding situations where it would not be appropriate to use a particular composition. Adverse side effects could also occur when the subject has, will be or is currently taking one or more other medications that may be incompatible with the composition, or the subject has, will be or is currently undergoing another treatment protocol or therapeutic regimen which would be incompatible with the composition and, therefore, instructions could include information regarding such incompatibilities.

[00130] Kits can additionally include other components. Each component of the kit can be enclosed within an individual container and all of the various containers can be within a single package. Invention kits can be designed for cold storage. [00131] The invention has been described herein using specific embodiments for the purposes of illustration only. It will be readily apparent to one of ordinary skill in the art, however, that the principles of the invention can be embodied in other ways. Therefore, the invention should not be regarded as being limited in scope to the specific embodiments disclosed.

EXAMPLES

Example 1

[00132] Effective immunity against a pathogen entails (i) the development of highly specific, neutralizing, and non-self reactive antibodies and T cells and (ii) results in the development of immune memory cells that patrol the body and provide lifelong protection. Immune memory cells are uniquely positioned to rapidly and robustly expand and neutralize a specific pathogen if repeat exposure occurs. Vaccines provide a mechanism to promote safe development of long-lived immune memory against a pathogen(s) by avoiding the deleterious effects of actual pathogen infection. The inventor approach activates and redirects the long-lived immune memory derived from vaccines to fight cancer.

[00133] Peptide antigens are used in combination with other cancer and cancer- immune-based therapies to increase efficacy of patient treatment. Peptide antigens disclosed herein are delivered in combination with viral vectors including oncolytic viruses like T-Vec (Imlygic). T-Vec is the first oncolytic virus approved in the US and has been shown of utility in the treatment of patients with recurrent melanoma.

[00134] Peptide antigens disclosed herein are cloned into different viruses, including the herpes simplex virus type 1 (HSV1) virus, adenovirus (AdV), adeno-associated virus (AAV) and vaccinia virus, for expression in tumor tissue to combine oncolytic potential with increased tumor immunogenicity. Adenovirus (AdV), adeno-associated virus (AAV) and vaccinia virus are in advanced clinical development. These viruses have potential for selective tumor-mediated killing through direct tumor injection or engineered tumor specificity after systemic delivery. [00135] CTLA-4 (Ipilumimab), PDL-1 and PD1 (Nivolumab / Pembrolizumab) are two presently approved targets of antibody-based immune checkpoint inhibitors. These antibodies non-specifically block inhibitory receptors on T cells that maintain T cells in an activated state. Recent publications highlight the efficacy of these therapies may be tied to the mutational burden of the specific tumor and in tumors with low mutational burden, checkpoint inhibitors may be of limited utility. Peptide antigens disclosed herein are delivered to the tumor in combination with checkpoint inhibitors to bring immune memory derived from childhood vaccines to more robustly kill cancerous and precancerous tissue.

[00136] Chimeric Antigen receptor T cell therapies are presently in advanced clinical trials for various cancers. These therapies entail the isolation of patient T cells and re- engineering of T-cell specificity to the target of choosing. While these therapies have shown therapeutic promise in single-cell type tumors such as B cell lymphomas, solid tumors that are under immune-suppression and lack a single marker for targeting are presently intractable. In particular instances, the introduction of peptide antigens disclosed herein and simultaneous engineering of T cells with specificity for the delivered epitopes enable robust and targeted killing of epitope expressing cells.

[00137] Several cytokine and TNF-super family based therapies are in advanced clinical development for the treatment of cancer. Specifically, tumor specific expression of cytokines like IL12 and TNF superfamily members such as OX40 reduce tumor immune suppression and promote inflammation. In fact, oncolytic virus therapies are in development in which IL12 and OX40 are expressed by the therapeutic virus. In particular instances, combination with peptide antigens disclosed herein increase T cell infiltration and activation in the tumor tissue.

[00138] Rituximab represents a particularly successful candidate in the treatment of B cell-based tumors such as non-Hodgkin's lymphoma. Therapeutic antibodies recognize surface antigens of the tumor tissue and induce immune responses through phagocytosis, complement deposition, and cell cytotoxicity. In particular instances, combined delivery of peptide antigens described herein with mAbs increase the immune potential of the tumor leading to increased killing of tumor tissue by the immune system. [00139] Popular developing therapies in clinical development utilize cancer-specific mutations to enable generation or expansion of tumor-specific immunity within a patient. In brief, patient cancer-specific mutations are identified by a variety of sequencing methods and mutation gene products are identified and assessed for the ability to be bound by HLA molecules or the existence of mutation-specific T cells within the donor. Vaccination of these peptides/antigens in combination with adjuvant and checkpoint blockers are then used to expand mutation specific T cells. Various tumors have lower mutational burden and therefore cancer vaccine approaches are of limited practical utility. In particular instances, combination of administration of patient mutation specific peptides with childhood vaccine peptide antigens improve the therapeutic potential against the tumor.

[00140] While not standardly considered an immune-based therapy, increasing evidence of an immune response against the cancer is seen upon tumor killing by radiation or chemotherapy approaches. This abscopal effect is tied to the presence of cancer-specific mutations that can generate adaptive immune responses in likeness to those used in cancer vaccines. In particular instances, selected delivery of vaccine-derived tumor tissue and co-treatment with radiation/chemo therapy lead to a broader more immunogenic based cell death that leads to improved cancer treatment.

[00141] In other approaches, T cells are brought into closer proximity to malignant tissue by fusion of two antibodies or generation of bi-specific antibodies. Such an approach has shown early clinical potential by combined target of CD 19 and T-cell markers such as CD3 to bring T cells in proximity to the cellular target and promote T- cell-mediated killing. In particular instances, delivery of peptide antigens described herein to target tissue and co-administration of BiTE to promote T-cell infiltration into the target tissue improve the frequency or concentration of T cells with potential to specifically kill the tumor tissue. Example 2

[00142] Methods for prediction of human HLA class I alleles were adapted from

published and validated methods from the La Jolla Institute for Allergy and Immunology. All 9- and 10-mer peptides were predicted for their binding affinity to 27 MHC class I molecules. A panel of 16 HLA A (A*01 :01, A*26:01, A*32:01, A*02:01, A*02:03, A*02:06, A*68:02, A*2301, A*24:02, A*03 :01, A* l l :01, A*30:01, A*31 :01, A*33 :01, and A*68:01) and 11 HLA B alleles (B*40:01, B*44:02, B*44:03, B*57:01, B*58:01, B* 15:01 B*07:02, B*35:01, B*51 :01, B*53 :01, and B*08:01) were selected,

which account for 97% of HLA A and B allelic variants in most ethnicities. Binding predictions were performed using the consensus prediction tool available on the IEDB web site (Accessed online at <URL:http:/www.iedb.org/>). For each allele and length combination, peptides from each included vaccine strain were selected if they were in the top 1% of binders. Redundant sequences across various vaccine strains were removed and non-redundant sequences are listed in Table 1.

[00143] The binding affinity of 15-mer peptides derived from childhood vaccines were predicted using the panel of 27 HLA class II DRB1, 3/4/5, DQA1/DQB1, and DPB 1 molecules that provide broad ethnic and geographic population coverage using a consensus prediction approach. Peptides with predicted binding scores in the top 20% for a given allele were considered potential binders. Peptides predicted to bind 13 or more HLA molecules at this threshold were considered promiscuous binders.

Example 3

[00144] The mechanism by which viruses infect their host is well understood in the art.

Following viral infection, viral genes can become incorporated into the host genome. This viral transformation event can lead to uncontrolled proliferation and the development of various diseases and disorders including cancer. Viral, parasitic and bacterial transformation or infection of healthy cells has been identified as a common underlying cause of a great number of human cancers. [00145] In cancers that have been linked to viral gene transformation, specific viral genes are incorporated into the genome of cancers cells and maintain expression within the cancerous cells throughout the lifecycle of the cancer cell. For example, in cervical cancer, which has been linked to infection by human papillomaviruses, transformation of viral genes E6 and E7 has been widely established.

[00146] Today, it is now known that about 15%-20% of cancers have a viral cause, including Burkitt's lymphoma and Kaposi sarcoma (Epstein-Barr virus); cervical cancer (human papillomavirus); liver cancer (hepatitis B and C viruses) and Merkel cell cancer (Merkel cell polyomavirus), which represent a few notable cancers caused by viral transformation with high incidence and impact to society.

[00147] Similarly, chronic inflammation triggered by bacteria, can lead to the production of DNA-damaging molecules that cause mutations; this, combined with signals to produce new cells and grow new blood vessels— hallmarks of wound healing— can create a fertile ground for the emergence and growth of cancer. For example, a clear link between bacterial infection and cancer was established in the early 2000s when it was shown that the bacterium Helicobacter pylorus is a major cause of gastric cancer. In addition, parasitic infections have been linked to certain types of cancer including bladder cancer.

[00148] In particular instances, specific expression of the peptide antigens in target cells is driven by viral or bacterial factors present only in the target cells.

Example 4

[00149] The measurement of pre-existing immune responses derived from childhood vaccines are performed to assess and quantify the presence of circulating antibodies and/or frequency of vaccine-specific immune cells in the individual. The proteins and/or peptides listed in Table 1 are used as part of a kit to specifically measure B cell response by antibody ELISA and/or the CD4 and CD8 T-cell response by cytokine ELISA or ELISPOT to inform the frequency and functionality of vaccine immune memory of the patient. The results obtained from use of the diagnostic kit inform whether a patient has sufficient immune memory for therapeutic application or would benefit from receipt of a booster vaccination prior to administration of the therapeutic to increase the frequency of vaccine-specific immune cells that recognize and promote an anti-tumor immune response.

TABLES

Table 1 . 642 Class I non-redundant predicted peptides derived from ORF22 of the Varicella zoster vaccine Oka strain (Merck). Peptides are 9 and 10 mer in length.

Varicella-zoster virus (strain Oka) ORF22 224 233 EEALSSAVTL

Varicella-zoster virus (strain Oka) ORF22 226 234 ALSSAVTLI

Varicella-zoster virus (strain Oka) ORF22 226 235 ALSSAVTLIY

Varicella-zoster virus (strain Oka) ORF22 227 235 LSSAVTLIY

Varicella-zoster virus (strain Oka) ORF22 233 241 LIYGSCDTY

Varicella-zoster virus (strain Oka) ORF22 233 242 LIYGSCDTYF

Varicella-zoster virus (strain Oka) ORF22 234 242 IYGSCDTYF

Varicella-zoster virus (strain Oka) ORF22 239 247 DTYFTDEQY

Varicella-zoster virus (strain Oka) ORF22 242 250 FTDEQYCEK

Varicella-zoster virus (strain Oka) ORF22 252 260 VTAQHPLLL

Varicella-zoster virus (strain Oka) ORF22 256 264 HPLLLSPPN

Varicella-zoster virus (strain Oka) ORF22 261 270 SPPNSTTIVL

Varicella-zoster virus (strain Oka) ORF22 262 270 PPNSTTIVL

Varicella-zoster virus (strain Oka) ORF22 272 280 KSSIVPLHQ

Varicella-zoster virus (strain Oka) ORF22 272 281 KSSIVPLHQN

Varicella-zoster virus (strain Oka) ORF22 283 292 GESVSLEATL

Varicella-zoster virus (strain Oka) ORF22 288 296 LEATLHSTL

Varicella-zoster virus (strain Oka) ORF22 291 300 TLHSTLTNTV

Varicella-zoster virus (strain Oka) ORF22 294 302 STLTNTVAL

Varicella-zoster virus (strain Oka) ORF22 296 305 LTNTVALDPR

Varicella-zoster virus (strain Oka) ORF22 299 308 TVALDPRCSY

Varicella-zoster virus (strain Oka) ORF22 303 311 DPRCSYSEV

Varicella-zoster virus (strain Oka) ORF22 305 314 RCSYSEVDPW

Varicella-zoster virus (strain Oka) ORF22 306 314 CSYSEVDPW

Varicella-zoster virus (strain Oka) ORF22 309 317 SEVDPWHAV

Varicella-zoster virus (strain Oka) ORF22 309 318 SEVDP HAVL

Varicella-zoster virus (strain Oka) ORF22 319 327 ETTSTGSGV

Varicella-zoster virus (strain Oka) ORF22 319 328 ETTSTGSGVL

Varicella-zoster virus (strain Oka) ORF22 326 335 GVLDCRRRRR

Varicella-zoster virus (strain Oka) ORF22 330 338 CRRRRRPSW

Varicella-zoster virus (strain Oka) ORF22 360 369 STDNLHKPA

Varicella-zoster virus (strain Oka) ORF22 366 374 KPAKKVLKF

Varicella-zoster virus (strain Oka) ORF22 383 392 KTQVAHVLPR

Varicella-zoster virus (strain Oka) ORF22 385 394 QVAHVLPRLR

Varicella-zoster virus (strain Oka) ORF22 394 402 REVANTPDV

Varicella-zoster virus (strain Oka) ORF22 395 403 EVANTPDVV

Varicella-zoster virus (strain Oka) ORF22 398 406 NTPDVVLNV

Varicella-zoster virus (strain Oka) ORF22 410 418 DTPESSPTF

Varicella-zoster virus (strain Oka) ORF22 415 424 SPTFSRN NV

Varicella-zoster virus (strain Oka) ORF22 419 428 SRNMNVGSSL

Varicella-zoster virus (strain Oka) ORF22 420 429 RNMNVGSSLK

Varicella-zoster virus (strain Oka) ORF22 421 429 N NVGSSLK

Varicella-zoster virus (strain Oka) ORF22 427 435 SLKDRKPFL

Varicella-zoster virus (strain Oka) ORF22 434 442 FLFEQSGDV

Varicella-zoster virus (strain Oka) ORF22 448 456 KLLQHGHEI

Varicella-zoster virus (strain Oka) ORF22 470 478 TVITGHTNV

Varicella-zoster virus (strain Oka) ORF22 472 480 ITGHTNVPI

Varicella-zoster virus (strain Oka) ORF22 472 481 ITGHTNVPIW

Varicella-zoster virus (strain Oka) ORF22 475 484 HTNVP!VWTR

Varicella-zoster virus (strain Oka) ORF22 476 484 TNVPIWVTR

Varicella-zoster virus (strain Oka) ORF22 478 486 VPIWVTRPL 98 Varicella-zoster virus (strain Oka) ORF22 478 487 VPIWVTRPLV

99 Varicella-zoster virus (strain Oka) ORF22 488 497 MPDEKDPLEL

100 Varicella-zoster virus (strain Oka) ORF22 493 501 DPLELFINL

101 Varicella-zoster virus (strain Oka) ORF22 495 503 LELFINLTI

102 Varicella-zoster virus (strain Oka) ORF22 495 504 LELFINLTIL

103 Varicella-zoster virus (strain Oka) ORF22 496 505 ELFINLTILR

104 Varicella-zoster virus (strain Oka) ORF22 497 505 LFINLTILR

105 Varicella-zoster virus (strain Oka) ORF22 501 509 LTILRLTGF

106 Varicella-zoster virus (strain Oka) ORF22 523 532 S VSDF!GPL

107 Varicella-zoster virus (strain Oka) ORF22 530 539 GPLGEILTGF

108 Varicella-zoster virus (strain Oka) ORF22 539 547 FPSAAELIR

109 Varicella-zoster virus (strain Oka) ORF22 539 548 FPSAAELIRV

1 10 Varicella-zoster virus (strain Oka) ORF22 543 551 AELIRVTSL

1 11 Varicella-zoster virus (strain Oka) ORF22 543 552 AEURVTSLi

1 12 Varicella-zoster virus (strain Oka) ORF22 544 552 ELIRVTSLI

1 13 Varicella-zoster virus (strain Oka) ORF22 552 561 ILTN PGAEY

1 14 Varicella-zoster virus (strain Oka) ORF22 553 561 LTN PGAEY

1 15 Varicella-zoster virus (strain Oka) ORF22 559 567 AEYAIKTVL

1 16 Varicella-zoster virus (strain Oka) ORF22 559 568 AEYAIKTVLR

1 17 Varicella-zoster virus (strain Oka) ORF22 560 568 EYAIKTVLR

1 18 Varicella-zoster virus (strain Oka) ORF22 571 580 CTiG LNAK

1 19 Varicella-zoster virus (strain Oka) ORF22 572 580 TIG LIIAK

120 Varicella-zoster virus (strain Oka) ORF22 575 583 LIIAKFGL

121 Varicella-zoster virus (strain Oka) ORF22 575 584 MLIIAKFGLV

122 Varicella-zoster virus (strain Oka) ORF22 576 584 LIIAKFGLV

123 Varicella-zoster virus (strain Oka) ORF22 587 595 RVQDTTGAL

124 Varicella-zoster virus (strain Oka) ORF22 597 606 AELDVLEADL

125 Varicella-zoster virus (strain Oka) ORF22 610 618 SPIDLYSRL

126 Varicella-zoster virus (strain Oka) ORF22 614 623 LYSRLSTGLI

127 Varicella-zoster virus (strain Oka) ORF22 617 625 RLSTGLISI

128 Varicella-zoster virus (strain Oka) ORF22 621 630 GLISILNSPI

129 Varicella-zoster virus (strain Oka) ORF22 628 636 SPIISHPGL

130 Varicella-zoster virus (strain Oka) ORF22 628 637 SPilSHPGLF

131 Varicella-zoster virus (strain Oka) ORF22 633 641 HPGLFAELI

132 Varicella-zoster virus (strain Oka) ORF22 638 646 AELIPTRTG

133 Varicella-zoster virus (strain Oka) ORF22 647 655 SLSERIRLL

134 Varicella-zoster virus (strain Oka) ORF22 649 658 SER!RLLCEL

135 Varicella-zoster virus (strain Oka) ORF22 653 662 RLLGELVSAR

136 Varicella-zoster virus (strain Oka) ORF22 657 665 ELVSARETR

137 Varicella-zoster virus (strain Oka) ORF22 657 666 ELVSARETRY

138 Varicella-zoster virus (strain Oka) ORF22 660 668 SARETRY R

139 Varicella-zoster virus (strain Oka) ORF22 664 673 TRYMREHTAL

140 Varicella-zoster virus (strain Oka) ORF22 665 673 RY REHTAL

141 Varicella-zoster virus (strain Oka) ORF22 665 674 RYMREHTALV

142 Varicella-zoster virus (strain Oka) ORF22 666 674 Y REHTALV

143 Varicella-zoster virus (strain Oka) ORF22 668 677 REHTALVSSV

144 Varicella-zoster virus (strain Oka) ORF22 670 678 HTALVSSVK

145 Varicella-zoster virus (strain Oka) ORF22 676 685 SVKALENALR

146 Varicella-zoster virus (strain Oka) ORF22 705 714 EETD!PPEEL

147 Varicella-zoster virus (strain Oka) ORF22 712 721 EELiRRVYEI

148 Varicella-zoster virus (strain Oka) ORF22 713 721 ELIRRVYEI 149 Varicella-zoster virus (strain Oka) ORF22 713 722 EL!RRVYE!R

150 Varicella-zoster virus (strain Oka) ORF22 717 725 RVYEIRSEV

151 Varicella-zoster virus (strain Oka) ORF22 719 727 YEIRSEVT

152 Varicella-zoster virus (strain Oka) ORF22 719 728 YEIRSEVTML

153 Varicella-zoster virus (strain Oka) ORF22 720 729 EIRSEVTMLL

154 Varicella-zoster virus (strain Oka) ORF22 723 731 SEVT LLTS

155 Varicella-zoster virus (strain Oka) ORF22 723 732 SEVTMLLTSA

156 Varicella-zoster virus (strain Oka) ORF22 724 733 EVTMLLTSAV

157 Varicella-zoster virus (strain Oka) ORF22 725 733 VT LLTSAV

158 Varicella-zoster virus (strain Oka) ORF22 727 736 MLLTSAVTEY

159 Varicella-zoster virus (strain Oka) ORF22 729 737 LTSAVTEYF

160 Varicella-zoster virus (strain Oka) ORF22 730 739 TSAVTEYFTR

161 Varicella-zoster virus (strain Oka) ORF22 731 739 SAVTEYFTR

162 Varicella-zoster virus (strain Oka) ORF22 734 742 TEYFTRGVL

163 Varicella-zoster virus (strain Oka) ORF22 734 743 TEYFTRGVLY

164 Varicella-zoster virus (strain Oka) ORF22 737 746 FTRGVLYSTR

165 Varicella-zoster virus (strain Oka) ORF22 750 759 AEQSPRRFRV

166 Varicella-zoster virus (strain Oka) ORF22 753 761 SPRRFRVAT

167 Varicella-zoster virus (strain Oka) ORF22 753 762 SPRRFRVATA

168 Varicella-zoster virus (strain Oka) ORF22 756 764 RFRVATAST

169 Varicella-zoster virus (strain Oka) ORF22 756 765 RFRVATASTA

170 Varicella-zoster virus (strain Oka) ORF22 758 767 RVATASTAPI

171 Varicella-zoster virus (strain Oka) ORF22 759 767 VATASTAPI

172 Varicella-zoster virus (strain Oka) ORF22 760 769 ATASTAP!QR

173 Varicella-zoster virus (strain Oka) ORF22 761 769 TASTAPIQR

174 Varicella-zoster virus (strain Oka) ORF22 763 771 STAPIQRLL

175 Varicella-zoster virus (strain Oka) ORF22 765 774 APiQRLLDSL

176 Varicella-zoster virus (strain Oka) ORF22 769 777 RLLDSLPEF

177 Varicella-zoster virus (strain Oka) ORF22 780 788 KLTAIISSL

178 Varicella-zoster virus (strain Oka) ORF22 782 790 TAIISSLSI

179 Varicella-zoster virus (strain Oka) ORF22 795 803 ETIQNLPVV

180 Varicella-zoster virus (strain Oka) ORF22 800 809 LPWSLLKEL

181 Varicella-zoster virus (strain Oka) ORF22 802 811 WSLLKELIK

182 Varicella-zoster virus (strain Oka) ORF22 813 822 GEDLNTDTAL

183 Varicella-zoster virus (strain Oka) ORF22 817 825 NTDTALVSW

184 Varicella-zoster virus (strain Oka) ORF22 821 829 ALVSWLSVV

185 Varicella-zoster virus (strain Oka) ORF22 830 838 GEAQTAGYL

186 Varicella-zoster virus (strain Oka) ORF22 833 841 QTAGYLSRR

187 Varicella-zoster virus (strain Oka) ORF22 841 850 REFDELSRTI

188 Varicella-zoster virus (strain Oka) ORF22 848 856 RTIKTINTR

189 Varicella-zoster virus (strain Oka) ORF22 851 860 KTINTRATQR

190 Varicella-zoster virus (strain Oka) ORF22 865 873 AELSCFNTL

191 Varicella-zoster virus (strain Oka) ORF22 865 874 AELSCFNTLS

192 Varicella-zoster virus (strain Oka) ORF22 884 892 YETYNNGEV

193 Varicella-zoster virus (strain Oka) ORF22 885 893 ETYNNGEVK

194 Varicella-zoster virus (strain Oka) ORF22 885 894 ETYNNGEVKY

195 Varicella-zoster virus (strain Oka) ORF22 891 899 EVKYPEITR

196 Varicella-zoster virus (strain Oka) ORF22 894 902 YPEITRDDL

197 Varicella-zoster virus (strain Oka) ORF22 894 903 YPEITRDDLL

198 Varicella-zoster virus (strain Oka) ORF22 909 918 ATDDLVRQIK

199 Varicella-zoster virus (strain Oka) ORF22 932 940 SIKRRLETR 200 Varicella-zoster virus (strain Oka) ORF22 934 942 KRRLETRLK

201 Varicella-zoster virus (strain Oka) ORF22 938 947 ETRLKEVQTY

202 Varicella-zoster virus (strain Oka) ORF22 940 948 RLKEVQTYA

203 Varicella-zoster virus (strain Oka) ORF22 943 952 EVQTYANEAR

204 Varicella-zoster virus (strain Oka) ORF22 953 961 TTQDTIKSR

205 Varicella-zoster virus (strain Oka) ORF22 953 962 TTQDTIKSRK

206 Varicella-zoster virus (strain Oka) ORF22 957 965 TIKSRKQAA

207 Varicella-zoster virus (strain Oka) ORF22 959 967 KSRKQAAYN

208 Varicella-zoster virus (strain Oka) ORF22 959 968 KSRKQAAYNK

209 Varicella-zoster virus (strain Oka) ORF22 965 974 AYNKLGGLLR

210 Varicella-zoster virus (strain Oka) ORF22 966 974 YNKLGGLLR

211 Varicella-zoster virus (strain Oka) ORF22 968 976 KLGGLLRPV

212 Varicella-zoster virus (strain Oka) ORF22 971 980 GLLRPVTGFV

213 Varicella-zoster virus (strain Oka) ORF22 972 980 LLRPVTGFV

214 Varicella-zoster virus (strain Oka) ORF22 974 982 RPVTGFVGL

215 Varicella-zoster virus (strain Oka) ORF22 994 1002 SELDVQGAL

216 Varicella-zoster virus (strain Oka) ORF22 997 006 DVQGALVNLR

217 Varicella-zoster virus (strain Oka) ORF22 1004 1012 NLRTKVLEA

218 Varicella-zoster virus (strain Oka) ORF22 1006 1014 RTKVLEAPV

219 Varicella-zoster virus (strain Oka) ORF22 1008 1016 KVLEAPVEI

220 Varicella-zoster virus (strain Oka) ORF22 1012 1020 APVEIRSQL

221 Varicella-zoster virus (strain Oka) ORF22 015 1024 EIRSQLTGDF

222 Varicella-zoster virus (strain Oka) ORF22 1016 1025 IRSQLTGDFW

223 Varicella-zoster virus (strain Oka) ORF22 1017 1025 RSQLTGDFW

224 Varicella-zoster virus (strain Oka) ORF22 1018 1026 SQLTGDFWA

225 Varicella-zoster virus (strain Oka) ORF22 1018 027 SQLTGDFWAL

226 Varicella-zoster virus (strain Oka) ORF22 1019 1027 QLTGDFWAL

227 Varicella-zoster virus (strain Oka) ORF22 1019 028 QLTGDFWALF

228 Varicella-zoster virus (strain Oka) ORF22 1020 1028 LTGDFWALF

229 Varicella-zoster virus (strain Oka) ORF22 023 032 DFWALFNQYR

230 Varicella-zoster virus (strain Oka) ORF22 1024 1032 FWALFNQYR

231 Varicella-zoster virus (strain Oka) ORF22 033 042 DiLEHPGNAR

232 Varicella-zoster virus (strain Oka) ORF22 1037 1045 HPGNARTSV

233 Varicella-zoster virus (strain Oka) ORF22 1037 046 HPGNARTSVL

234 Varicella-zoster virus (strain Oka) ORF22 1044 053 SVLGGLGACF

235 Varicella-zoster virus (strain Oka) ORF22 1053 062 FTA!iEiVP!

236 Varicella-zoster virus (strain Oka) ORF22 1057 066 iE!VP!PTEY

237 Varicella-zoster virus (strain Oka) ORF22 1058 1066 EIVPIPTEY

238 Varicella-zoster virus (strain Oka) ORF22 1058 067 EIVP!PTEYR

239 Varicella-zoster virus (strain Oka) ORF22 1062 1070 IPTEYRPSL

240 Varicella-zoster virus (strain Oka) ORF22 064 1073 TEYRPSLLAF

241 Varicella-zoster virus (strain Oka) ORF22 1065 1073 EYRPSLLAF

242 Varicella-zoster virus (strain Oka) ORF22 065 1074 EYRPSLLAFF

243 Varicella-zoster virus (strain Oka) ORF22 1080 1088 VLASDIATV

244 Varicella-zoster virus (strain Oka) ORF22 1093 1 101 ESESAINAV

245 Varicella-zoster virus (strain Oka) ORF22 093 1 102 ESESAINAW

246 Varicella-zoster virus (strain Oka) ORF22 1094 1 102 SESAINAVV

247 Varicella-zoster virus (strain Oka) ORF22 1 113 1 121 STVPALSFV

248 Varicella-zoster virus (strain Oka) ORF22 1 113 122 STVPALSFVL

249 Varicella-zoster virus (strain Oka) ORF22 1 115 124 VPALSFVLSL

250 Varicella-zoster virus (strain Oka) ORF22 1 116 1 125 PALSFVLSLY 251 Varicella-zoster virus (strain Oka) ORF22 1 117 1 125 ALSFVLSLY

252 Varicella-zoster virus (strain Oka) ORF22 1 117 26 ALSFVLSLYK

253 Varicella-zoster virus (strain Oka) ORF22 1 118 1 126 LSFVLSLYK

254 Varicella-zoster virus (strain Oka) ORF22 1 118 1 127 LSFVLSLYKK

255 Varicella-zoster virus (strain Oka) ORF22 1 122 1 131 LSLYKKYQAL

256 Varicella-zoster virus (strain Oka) ORF22 1 123 1 131 SLYKKYQAL

257 Varicella-zoster virus (strain Oka) ORF22 1 127 1 135 KYQALQQEI

258 Varicella-zoster virus (strain Oka) ORF22 1 133 1 141 QEITNTHKL

259 Varicella-zoster virus (strain Oka) ORF22 1 144 1 152 LQKQLGDDF

260 Varicella-zoster virus (strain Oka) ORF22 1 146 55 KQLGDDFSTL

261 Varicella-zoster virus (strain Oka) ORF22 1 154 1 163 TLAVSSGHLK

262 Varicella-zoster virus (strain Oka) ORF22 1 161 1 70 HLKFISSSNV

263 Varicella-zoster virus (strain Oka) ORF22 164 1 173 FiSSSNVDDY

264 Varicella-zoster virus (strain Oka) ORF22 1 165 1 173 ISSSNVDDY

265 Varicella-zoster virus (strain Oka) ORF22 1 165 74 ISSSNVDDYE

266 Varicella-zoster virus (strain Oka) ORF22 1 173 1 182 YEiNDAiLSI

267 Varicella-zoster virus (strain Oka) ORF22 1 174 1 182 EINDAILSI

268 Varicella-zoster virus (strain Oka) ORF22 1 185 1 193 NVHAL DTV

269 Varicella-zoster virus (strain Oka) ORF22 1 188 1 196 AL DTVKLV

270 Varicella-zoster virus (strain Oka) ORF22 1 194 1202 KLVEVELQK

271 Varicella-zoster virus (strain Oka) ORF22 207 1216 CIAGTSTLSR

272 Varicella-zoster virus (strain Oka) ORF22 1210 1219 GTSTLSRWK

273 Varicella-zoster virus (strain Oka) ORF22 1223 1231 KLVT AHEK

274 Varicella-zoster virus (strain Oka) ORF22 223 1232 KLVTMAHEKK

275 Varicella-zoster virus (strain Oka) ORF22 1236 1244 KVLITDCER

276 Varicella-zoster virus (strain Oka) ORF22 1244 1252 RAHKQQTTR

277 Varicella-zoster virus (strain Oka) ORF22 1247 1255 KQQTTRVLY

278 Varicella-zoster virus (strain Oka) ORF22 1249 1257 QTTRVLYER

279 Varicella-zoster virus (strain Oka) ORF22 249 258 QTTRVLYERW

280 Varicella-zoster virus (strain Oka) ORF22 1250 1258 TTRVLYERW

281 Varicella-zoster virus (strain Oka) ORF22 1252 1260 RVLYERWTR

282 Varicella-zoster virus (strain Oka) ORF22 1254 1262 LYERWTRDI

283 Varicella-zoster virus (strain Oka) ORF22 1261 1269 DIIACLEA

284 Varicella-zoster virus (strain Oka) ORF22 266 275 LEAMETRHVF

285 Varicella-zoster virus (strain Oka) ORF22 1267 1275 EA ETRHVF

286 Varicella-zoster virus (strain Oka) ORF22 1273 1281 HVFNGTELA

287 Varicella-zoster virus (strain Oka) ORF22 1273 282 HVFNGTELAR

288 Varicella-zoster virus (strain Oka) ORF22 1278 1286 TELARLRD

289 Varicella-zoster virus (strain Oka) ORF22 1280 1288 LARLRD AA

290 Varicella-zoster virus (strain Oka) ORF22 1286 1294 AAAGGFDI

291 Varicella-zoster virus (strain Oka) ORF22 293 302 DIHAVYPQAR

292 Varicella-zoster virus (strain Oka) ORF22 1298 1306 YPQARQVVA

293 Varicella-zoster virus (strain Oka) ORF22 29S 307 YPQARQWAA

294 Varicella-zoster virus (strain Oka) ORF22 1308 1316 CETTAVTAL

295 Varicella-zoster virus (strain Oka) ORF22 1310 3 9 TTAVTALDTV

296 Varicella-zoster virus (strain Oka) ORF22 131 1 1320 TAVTALDTVF

297 Varicella-zoster virus (strain Oka) ORF22 1312 321 AVTALDTVFR

298 Varicella-zoster virus (strain Oka) ORF22 1313 1321 VTALDTVFR

299 Varicella-zoster virus (strain Oka) ORF22 1331 340 NiPPPLALLR

300 Varicella-zoster virus (strain Oka) ORF22 1336 1344 LALLRGLTW

301 Varicella-zoster virus (strain Oka) ORF22 1342 1350 LTWFDDFSI 302 Varicella-zoster virus (strain Oka) ORF22 1346 1354 DDFSITAPV

303 Varicella-zoster virus (strain Oka) ORF22 348 357 FSITAPVFTV

304 Varicella-zoster virus (strain Oka) ORF22 1350 1358 ITAPVFTV

305 Varicella-zoster virus (strain Oka) ORF22 355 364 FTVMFPGVSI

306 Varicella-zoster virus (strain Oka) ORF22 1356 1364 TV FPGVSI

307 Varicella-zoster virus (strain Oka) ORF22 1359 1367 FPGVSIEGL

308 Varicella-zoster virus (strain Oka) ORF22 1359 368 FPGVSIEGLL

309 Varicella-zoster virus (strain Oka) ORF22 1368 1376 LLL RIRAV

310 Varicella-zoster virus (strain Oka) ORF22 36S 1377 LLLMRIRAW

311 Varicella-zoster virus (strain Oka) ORF22 1369 1377 LL RIRAVV

312 Varicella-zoster virus (strain Oka) ORF22 369 1378 LL RIRAWL

313 Varicella-zoster virus (strain Oka) ORF22 1370 1378 L RIRAVVL

314 Varicella-zoster virus (strain Oka) ORF22 370 379 LMRIRAWLL

315 Varicella-zoster virus (strain Oka) ORF22 1372 1380 RIRAVVLLS

316 Varicella-zoster virus (strain Oka) ORF22 382 391 DTSINGIPNY

317 Varicella-zoster virus (strain Oka) ORF22 1383 1391 TSINGIPNY

318 Varicella-zoster virus (strain Oka) ORF22 1383 392 TSINGIPNYR

319 Varicella-zoster virus (strain Oka) ORF22 1384 1392 SINGIPNYR

320 Varicella-zoster virus (strain Oka) ORF22 1388 1396 IPNYRD IL

321 Varicella-zoster virus (strain Oka) ORF22 1393 02 DMILRTSGDL

322 Varicella-zoster virus (strain Oka) ORF22 1397 1405 RTSGDLLQI

323 Varicella-zoster virus (strain Oka) ORF22 402 141 1 LLQIPALAGY

324 Varicella-zoster virus (strain Oka) ORF22 1403 141 1 LQIPALAGY

325 Varicella-zoster virus (strain Oka) ORF22 403 1412 LQiPALAGYV

326 Varicella-zoster virus (strain Oka) ORF22 405 41 ^■PALAGYVDF

327 Varicella-zoster virus (strain Oka) ORF22 1407 1415 ALAGYVDFY

328 Varicella-zoster virus (strain Oka) ORF22 407 416 ALAGYVDFYT

329 Varicella-zoster virus (strain Oka) ORF22 1409 1417 AGYVDFYTR

330 Varicella-zoster virus (strain Oka) ORF22 141 1 1419 YVDFYTRSY

331 Varicella-zoster virus (strain Oka) ORF22 1414 1422 FYTRSYDQF

332 Varicella-zoster virus (strain Oka) ORF22 4 423 FYTRSYDQFI

333 Varicella-zoster virus (strain Oka) ORF22 1424 1432 TESVTLSEL

334 Varicella-zoster virus (strain Oka) ORF22 1425 1433 ESVTLSELR

335 Varicella-zoster virus (strain Oka) ORF22 1446 1454 EANKALEEV

336 Varicella-zoster virus (strain Oka) ORF22 1449 1457 KALEEVTHV

337 Varicella-zoster virus (strain Oka) ORF22 1452 1460 EEVTHVRAH

338 Varicella-zoster virus (strain Oka) ORF22 1456 1464 HVRAHETAK

339 Varicella-zoster virus (strain Oka) ORF22 1456 465 HVRAHETAKL

340 Varicella-zoster virus (strain Oka) ORF22 1465 1473 LALKEGVFI

341 Varicella-zoster virus (strain Oka) ORF22 1473 1481 ITLPSEGLL

342 Varicella-zoster virus (strain Oka) ORF22 1477 1485 SEGLLIRAI

343 Varicella-zoster virus (strain Oka) ORF22 1480 1488 LLIRAIEYF

344 Varicella-zoster virus (strain Oka) ORF22 1483 1491 RAIEYFTTF

345 Varicella-zoster virus (strain Oka) ORF22 486 95 EYFTTFDHKR

346 Varicella-zoster virus (strain Oka) ORF22 1487 1495 YFTTFDHKR

347 Varicella-zoster virus (strain Oka) ORF22 1495 1503 RFIGTAYER

348 Varicella-zoster virus (strain Oka) ORF22 1500 1508 AYERVLQT

349 Varicella-zoster virus (strain Oka) ORF22 1503 151 1 RVLQT VDR

350 Varicella-zoster virus (strain Oka) ORF22 1506 1514 QT VDRDLK

351 Varicella-zoster virus (strain Oka) ORF22 1514 523 KEANAELAQF

352 Varicella-zoster virus (strain Oka) ORF22 1515 1523 EANAELAQF 353 Varicella-zoster virus (strain Oka) ORF22 1518 1526 AELAQFR V

354 Varicella-zoster virus (strain Oka) ORF22 5 8 527 AELAQFRMVC

355 Varicella-zoster virus (strain Oka) ORF22 1524 533 RMVCQATKNR

356 Varicella-zoster virus (strain Oka) ORF22 1525 1533 VCQATKNR

357 Varicella-zoster virus (strain Oka) ORF22 1533 1541 RAIQILQNI

358 Varicella-zoster virus (strain Oka) ORF22 1548 1556 TEQQEDVDF

359 Varicella-zoster virus (strain Oka) ORF22 1551 1559 QEDVDFTNL

360 Varicella-zoster virus (strain Oka) ORF22 1556 1564 FTNLKTLLK

361 Varicella-zoster virus (strain Oka) ORF22 560 569 KTLLKLTPPP

362 Varicella-zoster virus (strain Oka) ORF22 561 1570 TLLKLTPPPK

363 Varicella-zoster virus (strain Oka) ORF22 1562 1570 LLKLTPPPK

364 Varicella-zoster virus (strain Oka) ORF22 1566 1574 TPPPKTIAL

365 Varicella-zoster virus (strain Oka) ORF22 573 582 ALAIDRSTSV

366 Varicella-zoster virus (strain Oka) ORF22 1574 1582 LAIDRSTSV

367 Varicella-zoster virus (strain Oka) ORF22 1584 1592 DIVTQFALL

368 Varicella-zoster virus (strain Oka) ORF22 1604 1612 DIQAVDWMY

369 Varicella-zoster virus (strain Oka) ORF22 1629 1637 GTGPLHTYK

370 Varicella-zoster virus (strain Oka) ORF22 1634 1642 HTYKDRVDK

371 Varicella-zoster virus (strain Oka) ORF22 1638 647 DRVDKLYALR

372 Varicella-zoster virus (strain Oka) ORF22 1639 1647 RVDKLYALR

373 Varicella-zoster virus (strain Oka) ORF22 1642 1650 KLYALRTKL

374 Varicella-zoster virus (strain Oka) ORF22 643 1652 LYALRTKLDL

375 Varicella-zoster virus (strain Oka) ORF22 1647 1655 RTKLDLLRR

376 Varicella-zoster virus (strain Oka) ORF22 647 1656 RTKLDLLRRR

377 Varicella-zoster virus (strain Oka) ORF22 1652 1660 LLRRRIETG

378 Varicella-zoster virus (strain Oka) ORF22 1656 1664 RIETGEVTW

379 Varicella-zoster virus (strain Oka) ORF22 1660 1668 GEVTWDDAW

380 Varicella-zoster virus (strain Oka) ORF22 662 1671 VT DDAWTTF

381 Varicella-zoster virus (strain Oka) ORF22 1663 1671 TWDDAWTTF

382 Varicella-zoster virus (strain Oka) ORF22 1665 1673 DDAWTTFKR

383 Varicella-zoster virus (strain Oka) ORF22 1678 1686 LASGDTYA

384 Varicella-zoster virus (strain Oka) ORF22 1684 1692 TYATSVDSI

385 Varicella-zoster virus (strain Oka) ORF22 1685 1693 YATSVDSIK

386 Varicella-zoster virus (strain Oka) ORF22 1695 704 LQASASWDM

387 Varicella-zoster virus (strain Oka) ORF22 1704 1712 LCSEPEFF

388 Varicella-zoster virus (strain Oka) ORF22 1704 713 MLCSEPEFFL

389 Varicella-zoster virus (strain Oka) ORF22 1706 1714 CSEPEFFLL

390 Varicella-zoster virus (strain Oka) ORF22 1707 17 6 SEPEFFLLPV

391 Varicella-zoster virus (strain Oka) ORF22 1721 1729 RLQKKQQER

392 Varicella-zoster virus (strain Oka) ORF22 1730 739 KTALDVVLQK

393 Varicella-zoster virus (strain Oka) ORF22 1731 1739 TALDVVLQK

394 Varicella-zoster virus (strain Oka) ORF22 1741 1749 RQFEETASR

395 Varicella-zoster virus (strain Oka) ORF22 44 1 753 EETASRLRAL

396 Varicella-zoster virus (strain Oka) ORF22 1745 1753 ETASRLRAL

397 Varicella-zoster virus (strain Oka) ORF22 745 54 E1ASRLRALI

398 Varicella-zoster virus (strain Oka) ORF22 747 56 ASRLRALIER

399 Varicella-zoster virus (strain Oka) ORF22 1760 1768 ESDHDVLR

400 Varicella-zoster virus (strain Oka) ORF22 1768 1776 LLHDFDQF

401 Varicella-zoster virus (strain Oka) ORF22 1773 782 FDQFTHLPIW

402 Varicella-zoster virus (strain Oka) ORF22 1779 1787 LPIWIKTQY

403 Varicella-zoster virus (strain Oka) ORF22 1779 788 LPIWIKTQYM 404 Varicella-zoster virus (strain Oka) ORF22 781 790 IWIKTQYMTF

405 Varicella-zoster virus (strain Oka) ORF22 782 791 WIKTQYMTFR

406 Varicella-zoster virus (strain Oka) ORF22 1786 1794 QY TFRNLL

407 Varicella-zoster virus (strain Oka) ORF22 786 795 QYMTFRNLLM

408 Varicella-zoster virus (strain Oka) ORF22 1787 796 YMTFRNLLMV

409 Varicella-zoster virus (strain Oka) ORF22 1788 1796 TFRNLL V

410 Varicella-zoster virus (strain Oka) ORF22 1788 797 MTFRNLLMVR

411 Varicella-zoster virus (strain Oka) ORF22 1789 1797 TFRNLL VR

412 Varicella-zoster virus (strain Oka) ORF22 792 S01 NLL VRLGLY

413 Varicella-zoster virus (strain Oka) ORF22 1793 1801 LL VRLGLY

414 Varicella-zoster virus (strain Oka) ORF22 793 S02 LL VRLGLYA

415 Varicella-zoster virus (strain Oka) ORF22 795 S04 MVRLGLYASY

416 Varicella-zoster virus (strain Oka) ORF22 1799 1807 GLYASYAEI

417 Varicella-zoster virus (strain Oka) ORF22 1800 1808 LYASYAEIF

418 Varicella-zoster virus (strain Oka) ORF22 802 81 ASYAEiFPPA

419 Varicella-zoster virus (strain Oka) ORF22 805 814 AEiFPPASPhi

420 Varicella-zoster virus (strain Oka) ORF22 1808 1816 FPPASPNGV

421 Varicella-zoster virus (strain Oka) ORF22 1808 817 FPPASPNGVF

422 Varicella-zoster virus (strain Oka) ORF22 1809 1817 PPASPNGVF

423 Varicella-zoster virus (strain Oka) ORF22 1812 1820 SPNGVFAPI

424 Varicella-zoster virus (strain Oka) ORF22 817 1826 FAPIPAMSGV

425 Varicella-zoster virus (strain Oka) ORF22 1818 1826 APIPA SGV

426 Varicella-zoster virus (strain Oka) ORF22 1820 1828 IPA SGVCL

427 Varicella-zoster virus (strain Oka) ORF22 833 1842 RC!RARVAAF

428 Varicella-zoster virus (strain Oka) ORF22 1834 1842 CIRARVAAF

429 Varicella-zoster virus (strain Oka) ORF22 834 843 CIRARVAAFM

430 Varicella-zoster virus (strain Oka) ORF22 1844 1852 GEASVVQTF

431 Varicella-zoster virus (strain Oka) ORF22 1845 1853 EASVVQTFR

432 Varicella-zoster virus (strain Oka) ORF22 847 856 SVVQTFREAR

433 Varicella-zoster virus (strain Oka) ORF22 1848 1856 VVQTFREAR

434 Varicella-zoster virus (strain Oka) ORF22 853 862 REARSSIDAL

435 Varicella-zoster virus (strain Oka) ORF22 856 865 RSSIDALFGK

436 Varicella-zoster virus (strain Oka) ORF22 1857 1865 SSIDALFGK

437 Varicella-zoster virus (strain Oka) ORF22 1861 1869 ALFGKNLTF

438 Varicella-zoster virus (strain Oka) ORF22 861 870 ALFGKNLTFY

439 Varicella-zoster virus (strain Oka) ORF22 867 876 LTFYLDTDGV

440 Varicella-zoster virus (strain Oka) ORF22 1869 878 FYLDTDGVPL

441 Varicella-zoster virus (strain Oka) ORF22 1870 1878 YLDTDGVPL

442 Varicella-zoster virus (strain Oka) ORF22 1872 1880 DTDGVPLRY

443 Varicella-zoster virus (strain Oka) ORF22 1872 881 DTDGVPLRYR

444 Varicella-zoster virus (strain Oka) ORF22 1877 1885 PLRYRVCYK

445 Varicella-zoster virus (strain Oka) ORF22 1879 1887 RYRVCYKSV

446 Varicella-zoster virus (strain Oka) ORF22 881 1890 RVCYKSVGVK

447 Varicella-zoster virus (strain Oka) ORF22 1882 1890 VCYKSVGVK

448 Varicella-zoster virus (strain Oka) ORF22 1904 1912 RPALPDEGI

449 Varicella-zoster virus (strain Oka) ORF22 904 913 RPALPDEGIV

450 Varicella-zoster virus (strain Oka) ORF22 1913 1921 VEETTLSAL

451 Varicella-zoster virus (strain Oka) ORF22 1915 1923 ETTLSALRV

452 Varicella-zoster virus (strain Oka) ORF22 1922 931 RVANEVNELR

453 Varicella-zoster virus (strain Oka) ORF22 1923 1931 VANEVNELR

454 Varicella-zoster virus (strain Oka) ORF22 1925 934 NEVNELRIEY 455 Varicella-zoster virus (strain Oka) ORF22 1926 1934 EVNELRIEY

456 Varicella-zoster virus (strain Oka) ORF22 1933 942 EYESAIKSGF

457 Varicella-zoster virus (strain Oka) ORF22 1934 1942 YESAIKSGF

458 Varicella-zoster virus (strain Oka) ORF22 1937 1945 AIKSGFSAF

459 Varicella-zoster virus (strain Oka) ORF22 1940 1948 SGFSAFSTF

460 Varicella-zoster virus (strain Oka) ORF22 1941 950 GFSAFSTFVR

461 Varicella-zoster virus (strain Oka) ORF22 1942 1950 FSAFSTFVR

462 Varicella-zoster virus (strain Oka) ORF22 1943 952 SAFSTFVRHR

463 Varicella-zoster virus (strain Oka) ORF22 1944 1952 AFSTFVRHR

464 Varicella-zoster virus (strain Oka) ORF22 1948 1956 FVRHRHAEW

465 Varicella-zoster virus (strain Oka) ORF22 1950 1958 RHRHAEWGK

466 Varicella-zoster virus (strain Oka) ORF22 1955 1963 EWGKTNARR

467 Varicella-zoster virus (strain Oka) ORF22 1958 1966 KTNARRAIA

468 Varicella-zoster virus (strain Oka) ORF22 1965 1973 IAEIYAGLI

469 Varicella-zoster virus (strain Oka) ORF22 1966 1974 AEIYAGLIT

470 Varicella-zoster virus (strain Oka) ORF22 968 977 IYAGLITTTL

471 Varicella-zoster virus (strain Oka) ORF22 1974 983 TTTLTRQYGV

472 Varicella-zoster virus (strain Oka) ORF22 1975 1983 TTLTRQYGV

473 Varicella-zoster virus (strain Oka) ORF22 1976 985 TLTRQYGVHW

474 Varicella-zoster virus (strain Oka) ORF22 1977 1985 LTRQYGVHW

475 Varicella-zoster virus (strain Oka) ORF22 1979 1987 RQYGVHWDK

476 Varicella-zoster virus (strain Oka) ORF22 981 1990 YGVHWDKLIY

477 Varicella-zoster virus (strain Oka) ORF22 983 1992 VHWDKLIYSF

478 Varicella-zoster virus (strain Oka) ORF22 1984 1992 HWDKLIYSF

479 Varicella-zoster virus (strain Oka) ORF22 1989 1997 IYSFEKHHL

480 Varicella-zoster virus (strain Oka) ORF22 998 2007 TSV GNGLTK

481 Varicella-zoster virus (strain Oka) ORF22 1999 2007 SV GNGLTK

482 Varicella-zoster virus (strain Oka) ORF22 2007 2015 KPIQRRGDV

483 Varicella-zoster virus (strain Oka) ORF22 2020 2028 LTLSDIVTI

484 Varicella-zoster virus (strain Oka) ORF22 2021 2029 TLSDIVTIL

485 Varicella-zoster virus (strain Oka) ORF22 2021 2030 TLSD!VT!LV

486 Varicella-zoster virus (strain Oka) ORF22 2022 2030 LSDIVTILV

487 Varicella-zoster virus (strain Oka) ORF22 2042 2051 RLDLIKQHEY

488 Varicella-zoster virus (strain Oka) ORF22 2045 2054 LIKQHEYMAR

489 Varicella-zoster virus (strain Oka) ORF22 2047 2056 KQHEYMARTL

490 Varicella-zoster virus (strain Oka) ORF22 2049 2057 HEY ARTLR

491 Varicella-zoster virus (strain Oka) ORF22 2051 2059 Y ARTLRPV

492 Varicella-zoster virus (strain Oka) ORF22 2052 2060 ARTLRPVI

493 Varicella-zoster virus (strain Oka) ORF22 2054 2062 RTLRPVIEA

494 Varicella-zoster virus (strain Oka) ORF22 2055 2064 TLRPVIEAAF

495 Varicella-zoster virus (strain Oka) ORF22 2060 2068 IEAAFRGRL

496 Varicella-zoster virus (strain Oka) ORF22 2060 2069 IEAAFRGRLL

497 Varicella-zoster virus (strain Oka) ORF22 2063 2071 AFRGRLLVR

498 Varicella-zoster virus (strain Oka) ORF22 2064 2073 FRGRLLVRSL

499 Varicella-zoster virus (strain Oka) ORF22 2078 2087 KGNARAFFNA

500 Varicella-zoster virus (strain Oka) ORF22 2080 2088 NARAFFNAA

501 Varicella-zoster virus (strain Oka) ORF22 2082 2091 RAFFNAAPSK

502 Varicella-zoster virus (strain Oka) ORF22 2083 2091 AFFNAAPSK

503 Varicella-zoster virus (strain Oka) ORF22 2088 2096 APSKHKLPL

504 Varicella-zoster virus (strain Oka) ORF22 2104 2113 PTGGRIFAFR

505 Varicella-zoster virus (strain Oka) ORF22 2105 2113 TGGRIFAFR 506 Varicella-zoster virus (strain Oka) ORF22 2109 2117 IFAFR ADW

507 Varicella-zoster virus (strain Oka) ORF22 2110 2118 FAFR ADWK

508 Varicella-zoster virus (strain Oka) ORF22 2113 2121 R ADWKLVK

509 Varicella-zoster virus (strain Oka) ORF22 2122 2130 PQKITDPF

510 Varicella-zoster virus (strain Oka) ORF22 2122 2131 MPQKITDPFA

511 Varicella-zoster virus (strain Oka) ORF22 2125 2133 KITDPFAPW

512 Varicella-zoster virus (strain Oka) ORF22 2134 2142 QLSPPPGVK

513 Varicella-zoster virus (strain Oka) ORF22 2142 2150 KANVDAVTR

514 Varicella-zoster virus (strain Oka) ORF22 2151 2160 IMATDRLATI

515 Varicella-zoster virus (strain Oka) ORF22 2152 2160 ATDRLATI

516 Varicella-zoster virus (strain Oka) ORF22 2156 2165 RLAT!TVLGR

517 Varicella-zoster virus (strain Oka) ORF22 2158 2166 ATITVLGR

518 Varicella-zoster virus (strain Oka) ORF22 2165 2 74 R CLPPISLV

519 Varicella-zoster virus (strain Oka) ORF22 2168 2176 LPPISLVS

520 Varicella-zoster virus (strain Oka) ORF22 2168 2177 LPPISLVSMW

521 Varicella-zoster virus (strain Oka) ORF22 2169 2177 PPISLVS W

522 Varicella-zoster virus (strain Oka) ORF22 2171 2180 ISLVSMWNTL

523 Varicella-zoster virus (strain Oka) ORF22 2176 2185 M TLQPEEF

524 Varicella-zoster virus (strain Oka) ORF22 2179 2187 TLQPEEFAY

525 Varicella-zoster virus (strain Oka) ORF22 2185 2193 FAYRTQDDV

526 Varicella-zoster virus (strain Oka) ORF22 2189 2197 TQDDVDIIV

527 Varicella-zoster virus (strain Oka) ORF22 2202 2210 DLSSTLNAR

528 Varicella-zoster virus (strain Oka) ORF22 2203 221 1 LSSTLNARF

529 Varicella-zoster virus (strain Oka) ORF22 2213 2222 TAPSNTTLEW

530 Varicella-zoster virus (strain Oka) ORF22 2214 2222 APSNTTLEW

531 Varicella-zoster virus (strain Oka) ORF22 2218 2226 TTLEWNTDR

532 Varicella-zoster virus (strain Oka) ORF22 22 8 2227 TTLEWNTDRK

533 Varicella-zoster virus (strain Oka) ORF22 2233 2241 YIQTGATTV

534 Varicella-zoster virus (strain Oka) ORF22 2233 2242 YIQTGATTVF

535 Varicella-zoster virus (strain Oka) ORF22 2234 2242 IQTGATTVF

536 Varicella-zoster virus (strain Oka) ORF22 2239 2247 TTVFTVTGA

537 Varicella-zoster virus (strain Oka) ORF22 2239 2248 TTVFTVTGAA

538 Varicella-zoster virus (strain Oka) ORF22 2240 2248 TVFTVTGAA

539 Varicella-zoster virus (strain Oka) ORF22 2258 2267 FDIATTAILF

540 Varicella-zoster virus (strain Oka) ORF22 2259 2267 DIATTAILF

541 Varicella-zoster virus (strain Oka) ORF22 2262 2271 TTA!LFGAPL

542 Varicella-zoster virus (strain Oka) ORF22 2264 2272 AILFGAPLV

543 Varicella-zoster virus (strain Oka) ORF22 2265 2273 ILFGAPLVI

544 Varicella-zoster virus (strain Oka) ORF22 2267 2275 FGAPLVIA

545 Varicella-zoster virus (strain Oka) ORF22 2269 2277 APLVIA EL

546 Varicella-zoster virus (strain Oka) ORF22 2271 2280 LVIAMELTSV

547 Varicella-zoster virus (strain Oka) ORF22 2272 2280 VIA ELTSV

548 Varicella-zoster virus (strain Oka) ORF22 2273 2281 IA ELTSVF

549 Varicella-zoster virus (strain Oka) ORF22 2300 2308 ATDSGISSA

550 Varicella-zoster virus (strain Oka) ORF22 2305 2313 ISSAVSPDI

551 Varicella-zoster virus (strain Oka) ORF22 2307 23 6 SAVSPDIVSW

552 Varicella-zoster virus (strain Oka) ORF22 2308 2316 AVSPDIVSW

553 Varicella-zoster virus (strain Oka) ORF22 23 9 2328 RLLHMDPHPI

554 Varicella-zoster virus (strain Oka) ORF22 2320 2328 LLH DPHPI

555 Varicella-zoster virus (strain Oka) ORF22 2326 2334 HPIENACLI

556 Varicella-zoster virus (strain Oka) ORF22 2326 2335 HPIENACLIV 557 Varicella-zoster virus (strain Oka) ORF22 2328 2337 IENACLIVQL

558 Varicella-zoster virus (strain Oka) ORF22 2334 2343 IVQLEKLSAL

559 Varicella-zoster virus (strain Oka) ORF22 2335 2343 VQLEKLSAL

560 Varicella-zoster virus (strain Oka) ORF22 2339 2347 KLSALIANK

561 Varicella-zoster virus (strain Oka) ORF22 2358 2367 LLDEHMNPSY

562 Varicella-zoster virus (strain Oka) ORF22 2360 2369 DEHMNPSYVL

563 Varicella-zoster virus (strain Oka) ORF22 2361 2370 EHMNPSYVLW

564 Varicella-zoster virus (strain Oka) ORF22 2362 2370 H NPSYVLW

565 Varicella-zoster virus (strain Oka) ORF22 2363 2372 MNPSYVLWER

566 Varicella-zoster virus (strain Oka) ORF22 2364 2372 NPSYVLWER

567 Varicella-zoster virus (strain Oka) ORF22 2372 2381 RKDS!PAPDY

568 Varicella-zoster virus (strain Oka) ORF22 2374 2382 DSIPAPDYV

569 Varicella-zoster virus (strain Oka) ORF22 2376 2384 IPAPDYVVF

570 Varicella-zoster virus (strain Oka) ORF22 2376 2385 IPAPDYWFW

571 Varicella-zoster virus (strain Oka) ORF22 2386 2395 GPESLIDLPY

572 Varicella-zoster virus (strain Oka) ORF22 2387 2395 PESLIDLPY

573 Varicella-zoster virus (strain Oka) ORF22 2394 2403 PYiDSDEDSF

574 Varicella-zoster virus (strain Oka) ORF22 2403 241 1 FPSCPDDPF

575 Varicella-zoster virus (strain Oka) ORF22 2403 24 2 FPSCPDDPFY

576 Varicella-zoster virus (strain Oka) ORF22 2404 2412 PSCPDDPFY

577 Varicella-zoster virus (strain Oka) ORF22 2406 24 5 CPDDPFYSQI

578 Varicella-zoster virus (strain Oka) ORF22 241 1 2419 FYSQIIAGY

579 Varicella-zoster virus (strain Oka) ORF22 2430 2439 TDFYPTEPLF

580 Varicella-zoster virus (strain Oka) ORF22 2431 2439 DFYPTEPLF

581 Varicella-zoster virus (strain Oka) ORF22 2438 2447 LFKSPVQWR

582 Varicella-zoster virus (strain Oka) ORF22 2445 2453 VVRSSKCKK

583 Varicella-zoster virus (strain Oka) ORF22 2448 2456 SSKCKK PV

584 Varicella-zoster virus (strain Oka) ORF22 2454 2462 PVQPVQPA

585 Varicella-zoster virus (strain Oka) ORF22 2454 2463 MPVQPVQPAQ

586 Varicella-zoster virus (strain Oka) ORF22 2466 2474 QPAQPAQPV

587 Varicella-zoster virus (strain Oka) ORF22 2472 2480 QPVQPAQPI

588 Varicella-zoster virus (strain Oka) ORF22 2478 2486 QPIEPGTQI

589 Varicella-zoster virus (strain Oka) ORF22 2478 2487 QPiEPGTQIV

590 Varicella-zoster virus (strain Oka) ORF22 2483 2492 GTQIVVQNFK

591 Varicella-zoster virus (strain Oka) ORF22 2484 2492 TQIVVQNFK

592 Varicella-zoster virus (strain Oka) ORF22 2484 2493 TQIWQNFKK

593 Varicella-zoster virus (strain Oka) ORF22 2493 2501 KPQSVKTTL

594 Varicella-zoster virus (strain Oka) ORF22 2496 2504 SVKTTLSQK

595 Varicella-zoster virus (strain Oka) ORF22 2500 2509 TLSQKD!PLY

596 Varicella-zoster virus (strain Oka) ORF22 2501 2509 LSQKDIPLY

597 Varicella-zoster virus (strain Oka) ORF22 25 0 25 9 VETESETAVL

598 Varicella-zoster virus (strain Oka) ORF22 2512 2520 TESETAVLI

599 Varicella-zoster virus (strain Oka) ORF22 2520 2528 IPKQLTTSI

600 Varicella-zoster virus (strain Oka) ORF22 2525 2534 TTSIKTTVCK

601 Varicella-zoster virus (strain Oka) ORF22 2526 2534 TSIKTTVCK

602 Varicella-zoster virus (strain Oka) ORF22 2537 2546 TPPNNQLSDW

603 Varicella-zoster virus (strain Oka) ORF22 2538 2546 PPNNQLSDW

604 Varicella-zoster virus (strain Oka) ORF22 2551 2560 QGNQTLNQAF

605 Varicella-zoster virus (strain Oka) ORF22 2554 2562 QTLNQAFNK

606 Varicella-zoster virus (strain Oka) ORF22 2562 2570 KPILEITSI

607 Varicella-zoster virus (strain Oka) ORF22 2569 2578 SIPTDDSiSY 608 Varicella-zoster virus (strain Oka) ORF22 2570 2578 IPTDDSISY

609 Varicella-zoster virus (strain Oka) ORF22 2573 2581 DDSISYRTW

610 Varicella-zoster virus (strain Oka) ORF22 2575 2584 SISYRTWiEK

611 Varicella-zoster virus (strain Oka) ORF22 2576 2584 ISYRTWIEK

612 Varicella-zoster virus (strain Oka) ORF22 2597 2605 R YNSKTVF

613 Varicella-zoster virus (strain Oka) ORF22 2597 2606 RMYNSKTVFH

614 Varicella-zoster virus (strain Oka) ORF22 2600 2608 NSKTVFHPV

615 Varicella-zoster virus (strain Oka) ORF22 2606 2615 HPVNNQLPSW

616 Varicella-zoster virus (strain Oka) ORF22 2612 2620 LPSWVDTAA

617 Varicella-zoster virus (strain Oka) ORF22 2622 2631 APQTDLLTNY

618 Varicella-zoster virus (strain Oka) ORF22 2624 2632 QTDLLTNYK

619 Varicella-zoster virus (strain Oka) ORF22 2632 2640 KTRQPSPNF

620 Varicella-zoster virus (strain Oka) ORF22 2634 2642 RQPSPNFPR

621 Varicella-zoster virus (strain Oka) ORF22 2639 2647 NFPRDVHTW

622 Varicella-zoster virus (strain Oka) ORF22 2640 2649 FPRDVHTWGV

623 Varicella-zoster virus (strain Oka) ORF22 2646 2654 TWGVSSNPF

624 Varicella-zoster virus (strain Oka) ORF22 2650 2659 SSNPFNSPNR

625 Varicella-zoster virus (strain Oka) ORF22 2675 2683 SESENSIVL

626 Varicella-zoster virus (strain Oka) ORF22 2677 2685 SENSIVLSL

627 Varicella-zoster virus (strain Oka) ORF22 2677 2686 SE SIVLSLD

628 Varicella-zoster virus (strain Oka) ORF22 2687 2695 EHRSCRVPR

629 Varicella-zoster virus (strain Oka) ORF22 2689 2698 RSCRVPRHVR

630 Varicella-zoster virus (strain Oka) ORF22 2696 2704 HVRVVNADV

631 Varicella-zoster virus (strain Oka) ORF22 2701 27 0 NADVVTGRRY

632 Varicella-zoster virus (strain Oka) ORF22 2703 2712 DVVTGRRYVR

633 Varicella-zoster virus (strain Oka) ORF22 2704 2712 VVTGRRYVR

634 Varicella-zoster virus (strain Oka) ORF22 2728 2737 R iDNVRYTR

635 Varicella-zoster virus (strain Oka) ORF22 2729 2737 IDNVRYTR

636 Varicella-zoster virus (strain Oka) ORF22 2729 2738 MIDNVRYTRK

637 Varicella-zoster virus (strain Oka) ORF22 2739 2747 LL DHTEDI

638 Varicella-zoster virus (strain Oka) ORF22 2744 2753 TEDiFQGLGY

639 Varicella-zoster virus (strain Oka) ORF22 2745 2753 EDIFQGLGY

640 Varicella-zoster virus (strain Oka) ORF22 2746 2754 DIFQGLGYV

641 Varicella-zoster virus (strain Oka) ORF22 2746 2755 DiFGGLGYVK

642 Varicella-zoster virus (strain Oka) ORF22 2753 2762 YVKLLLDGTY

Claims

CLAIMS What is claimed is:

1. A method of treating cancer comprising:

a) providing a subject having or suspected of having a cancer; and b) administering a vector to the subject, wherein the vector directs expression of one or more peptide antigens on a target cell of the subject, wherein a memory or recall immune response is elicited against the one or more peptide antigens.

2. A method of treating cancer comprising:

a) providing a subject having or suspected of having a cancer; and b) administering a composition to the subject, wherein the composition comprises one or more peptide antigens,

wherein a memory or recall immune response is elicited against the one or more peptide antigens.

3. The method of claim 1 or 2, wherein from 1 day to 100 years prior to (b), the subject was vaccinated against a pathogen.

4. The method of claim 3, wherein prior to (b), the subject was vaccinated against chickenpox, measles, mumps, rubella, polio, or shingles/varicella zoster; a commercially available vaccine against another pathogen; one or more peptides listed in Table 1; or one or more peptides derived from a pathogen.

5. The method of any one of claims 1 to 4, wherein the administering elicits a recall immune response directed against the target cell presenting said peptide antigens, against the one or more peptide antigens, against chickenpox, measles, mumps, rubella, polio, or shingles/varicella zoster or against one or more peptide antigens derived from chickenpox, measles, mumps, rubella, polio, or shingles/varicella zoster.

6. The method of any one of claims 1 to 5, wherein the subject is further administered one or more anti-cancer therapies prior to, concurrently with, or after the administering of (b).

7. The method of claim 6, wherein the anti-cancer therapy comprises surgical resection, administering radiation therapy, chemotherapy or an immunotherapy which can be administered separately or in combination.

8. The method of claim 7, wherein the radiation therapy comprises external beam radiation, proton therapy, or internal radiation therapy.

9. The method of claim 7, wherein the immunotherapy comprises (i) chimeric antigen receptor (CAR)-T immunotherapy and optionally (ii) wherein the CAR-T immunotherapy comprises administering CAR T-cells configured to specifically bind to and kill the target cell.

10. The method of any one of claims 1 to 9, wherein the one or more peptide antigens bind to MHC class I or MHC class II and recall CD8 T-cell or CD4 T-cell responses.

11. The method of claim 7, wherein the immunotherapy comprises administering an antibody or antibody fragment that specifically binds to a tumor marker.

12. The method of claim 7 or 11, wherein the immunotherapy comprises administering an antibody or antibody fragment that specifically binds to CD20, CD30, CD33, CD47 (SIRP-1 alpha soluble receptor), CD52, CD138, CD274, CD279, PD-L1, CTLA-4, programmed cell death 1 (PD-1), CD33, EGFR, ERBB2 (CD340), ERBB3, VEGF, VEGFR, GM-2, gp-100, EPCAM, CD19, CD3, CEA, gpA33, mucins, TAG-72, CAIX, PSMA, folate-binding protein, GD2, GD3, Integrin _V_3, Integrin 5 1, IGF1R, EPHA3, TRAILRl, TRAILR2, RANKL, FAP, Tenascin, and/or administering cytokines, modified cytokines, chemokines, or toll-like receptors agonists, wherein the cytokines may optionally be selected from 11-2, 11-12, and IL- 15.

13. The method of claim 7, 11 or 12, wherein the immunotherapy comprises

administering cytokines, modified cytokines, chemokines, or toll-like receptors agonists, alone or in combination with other anti-cancer therapies, and wherein the cytokines may optionally be selected from 11-2, 11-12, and IL-15.

14. The method of claim 7, wherein the immunotherapy comprises administering an antibody or T cell that binds an immune checkpoint protein.

15. The method of any one of claims 3 to 14, wherein the peptide antigen is derived from the pathogen.

16. The method of any one of claims 3 to 15, wherein the pathogen is a human pathogen or non-human pathogen, or wherein the peptide antigen is conserved between human and another species, or wherein the peptide antigen cross-reacts between human and another species.

17. The method of any one of claims 3 to 16, wherein the pathogen is selected from a virus, bacteria, parasite or protozoa.

18. The method of any one of claims 3 to 17, wherein the pathogen is a virus selected from the order Flaviviridae, Retroviridae, Orthomyxoviridae, Arenaviridae, and

Mononegavirales.

19. The method of any one of claims 3 to 18, wherein the pathogen is a virus selected from the family Togaviridae, Reoviridae, picornaviridae, herpesviridae and Bunyaviridae.

20. The method of any one of claims 3 to 19, wherein the pathogen is a virus from the family Reoviridae.

21. The method of any one of claims 1 to 20, wherein the target cell is a cancer cell or neoplastic cell.

22. The method of any one of claims 1 to 21, wherein the target cell is a metastatic cancerous cell.

23. The method of claim 21 or 22, wherein the cancer cell or neoplastic cell is selected from a carcinoma, sarcoma, neuroblastoma, cervical cancer cell, hepatocellular cancer cell, bladder cancer cell, mesothelioma, glioblastoma, myeloma, lymphoma, neoplastic

lymphocyte, adenoma, adenocarcinoma, glioma, glioblastoma, retinoblastoma, astrocytoma, oligodendrocytoma, meningioma, melanoma, lymphosarcoma, liposarcoma, osteosarcoma, chondrosarcoma, leiomyosarcoma, rhabdomyosarcoma or fibrosarcoma.

24. The method of claim 23, wherein the cancer cell or neoplastic cell is a carcinoma or sarcoma.

25. The method of any one of claims 1 to 24, wherein the target cell is a cell that is or has been infected with a virus, bacteria, parasite or protozoa.

26. The method of any one of claims 1 to 25, wherein the one or more peptide antigens are selected from a peptide listed in Table 1, or a subsequence, homologue, variant or derivative thereof.

27. The method of any one of claims 1 to 26, wherein the subject is a mammal,

28. The method of any one of claims 1 to 26, wherein the subject is a non-human mammal.

29. The method of any one of claims 1 to 26, wherein the subject is a human.

30. The method of any one of claims 2 or 29, wherein prior to b), the subject was infected with the pathogen.

31. The method of any one of claims 1 to 30, wherein the cancer is a neoplasia derived from lung, thyroid, head or neck, nasopharynx, throat, nose, sinus, brain, spine, breast, adrenal gland, pituitary gland, thyroid, lymph, mouth, esophagus, stomach, duodenum, ileum, jejunum intestine, colon, rectum, uterus, urethra, ovary, cervix, endometrium, bladder, testicle, penis, prostate, kidney, pancreas, liver, bone, bone marrow, lymph, blood, muscle, or skin.

32. The method of any one of claims 1 to 30, wherein the cancer is selected from carcinoma, sarcoma, neuroblastoma, hepatocellular cancer, mesothelioma, glioblastoma, myeloma, lymphoma, myeloma, leukemia, adenoma, adenocarcinoma, glioma, glioblastoma, retinoblastoma, astrocytoma, oligodendrocytoma, meningioma, melanoma, cervical cancer, breast cancer, liver cancer, pancreatic cancer, brain cancer, lung cancer, skin cancer, ovarian cancer, and testicular cancer.

33. The method of any one of claims 1 to 30, wherein the cancer is an infection-induced cancer selected from hepatocellular carcinoma, cervical cancer, head and neck squamous cell carcinoma, adult T-cell leukemia/lymphoma, Burkitt lymphoma, Merkel cell carcinoma, Kaposi sarcoma, bladder cancer and gastric cancer.

34. The method of any one of claims 1 to 30, wherein the cancer comprises a low mutational burden.

35. The method of claim 34, wherein the cancer of low mutational burden comprises one or more of pilocytic astrocytoma, ALL, medulloblastoma, kidney chromophobe, thyroid, CLL, neuroblastoma, glioblastoma, and pancreatic cancer.

36. The method of claim 1, wherein the vector selectively directs expression of the one or more peptide antigens on the target cell.

37. The method of claim 1 or 36, wherein the vector directs expression of the one or more peptide antigens on the cell surface of the target cell.

38. The method of any one of claims 1 to 37, wherein the one or more peptide antigens are expressed or presented on the cell surface of the target cell.

39. The method of claim 2, wherein the vector comprises a nucleic acid encoding the one or more peptide antigens.

40. The method of claim 2 or 39, wherein the vector comprises a promoter operatively linked to the nucleic acid encoding the one or more peptides, and/or the vector is a replicating or non-replicating vector.

41. The method of claim 40, wherein the promoter is inducible by a factor.

42. The method of claim 41, wherein the factor is derived from the pathogen.

43. The method of claim 41, wherein the factor is a mutated human protein.

44. The method of claim 41, wherein the factor is one or more viral proteins.

45. The method of any one of claims 41 to 44, wherein the factor is a viral transcription factor.

46. The method of any one of claims 1 to 46, wherein the administering of (b) comprises administering nano-carriers, micro-carriers, microparticles, nanoparticles, liposomes, exosomes or recombinant virus to the subject, wherein the recombinant virus is a replicating or non-replicating virus.

47. The method of claim 46, wherein the microparticles, nanoparticles, liposomes, exosomes or recombinant virus comprise the vector.

48. The method of claim 46 or 47, wherein the administering of (b) comprises selectively delivering the nano-carriers, micro-carriers, microparticles, nanoparticles, liposomes, exosomes or recombinant virus to the target cell.

49. The method of claim 1, wherein the administering of (b) comprises administering a nucleic acid to the subject, wherein the nucleic acid comprises the vector.

50. The method of claim 1, wherein the vector is a plasmid.

51. The method of claim 1, wherein the vector is a linear nucleic acid molecule.

52. The method of claim 1, wherein the vector comprises a CRISPR element.

53. The method of claim 1, wherein the vector is configured to express (CRISPR- associated protein-9 nuclease) CAS9.

54. The method of claims 1, wherein the vector is integrated into the target cell by a method comprising CRISPR and (CRISPR-associated protein-9 nuclease) CAS9.

55. The method of any one of claims 1 to 54, wherein the administering comprises direct intra-tumoral injection, peri -tumoral, intravesical (bladder), or stereotactic (glioblastoma) administration, and wherein the intravesical administration is optionally intravesical administration comprising use of a urethral catheter.

56. The method of any one of claims 1 to 54, wherein the administering comprises intravenous injection, intraperitoneal injection, subcutaneous injection, intramuscular injection, bolus injection or slow perfusion.

57. The method of any one of claims 1 to 56, further comprising, concomitant with, or after b):

c) initiating, eliciting, promoting, or enhancing an immune response in the subject.

58. The method of claim 57, wherein the immune response is directed against the target cell and/or target antigen.

59. The method of claim 57 or 58, wherein the eliciting of (c) comprises initiating, eliciting, promoting or enhancing a recall response in the subject to the one or more peptide antigens.

60. The method of any one of claims 57 to 59, wherein the eliciting of (c) comprises administering a vaccine to the subject alone or in combination with immunostimulants.

61. The method of claim 60, wherein the vaccine is selected from a vaccine for chickenpox, measles, mumps, rubella, and polio.

62. The method of any one of claims 57 to 61, wherein the eliciting of (c) comprises administering a pharmaceutical composition to the subject, wherein the pharmaceutical composition comprises at least one of the one or more of the peptide antigens.

63. The method of claim 62, wherein the pharmaceutical composition comprises an adjuvant, or formulation with liposome, nano- or micro-particles or any other pharmaceutically acceptable compositions for administration.

64. The method of any one of claims 57 to 63, wherein the eliciting of (c) comprises administering an agent that modulates an immune response in the subject.

65. The method of claim 64, wherein the agent increases, enhances, promotes or elicits an innate immune response.

66. The method of claim 64 or 65, wherein the agent comprises a checkpoint blocker.

67. The method of any one of claims 64 or 66, wherein the agent increases, enhances, promotes or elicits a recall immune response.

68. The method of any one of claims 64 to 67, wherein the agent comprises an antibody.

69. The method of claim 68, wherein the antibody specifically binds to the one or more peptide antigens.

70. The method of any one of claims 64 to 69, wherein the agent comprises a nucleic acid, synthetic chemical, or small molecule.

71. The method of any one of claims 1 to 70, further comprising administering a checkpoint blocker.

72. The method of any one of claims 1 to 70, further comprising administering an agent to improve or abet antigen presentation through phagocytosis, endoplasmic reticulum based protein processing, peptide:MHC loading, and MHC surface expression.

73. The method of any one of claims 1 to 72, further comprising administering TAP to the target cell, wherein the TAP promotes peptide:MHC loading and expression.

74. The method of claim 2, wherein the composition comprises an adjuvant.

75. The method of claim 2, wherein the composition comprises exosomes.

76. The method of claim 2, wherein the composition comprises a nano-carrier, micro- carrier, microparticle, nanoparticle, or liposome.

77. The method of claim 76, wherein the microparticle, nanoparticle, or liposome configured to selectively deliver the one or more peptides to the target cell.

78. A pharmaceutical composition comprising one or more of a peptide listed in Table 1.

79. The composition of claim 78, further comprising an adjuvant.

80. A pharmaceutical composition comprising a vector configured to direct expression of one or more peptide antigens on a target cell of a subject, wherein the one or more peptide antigens is selected from a peptide listed in Table 1.

81. A diagnostic tool for measuring immune response to a vaccine or recall immunity to a target cell comprising measuring an immune response to one or more peptides listed Table 1.

82. The diagnostic tool of claim 81, wherein the measurement of recall immunity is prior to administration of a peptide listed in Table 1.

83. The diagnostic tool of claim 81, wherein the measurement of recall immunity is prior to administration of a vector configured to expresses at least one peptide listed in Table 1.

84. The method of claim 1 or 2 wherein the subject is vaccinated prior to, concurrently with, or after the administering of (b).

85. The method of claim 84, wherein the vaccination is a booster vaccination.

86. The method of claim 85, wherein the booster vaccination comprises at least one peptide listed in Table 1.

87. The method of claim 85, wherein the booster vaccination is a booster vaccination against chickenpox, measles, mumps, rubella, or polio.

88. The method of any one of claims 6 to 13, wherein the anti-cancer therapy comprises administering combinations of one or more small molecules, immune checkpoint inhibitors optionally selected from IDO/TDO inhibitors, and epigenetic regulators such as HDAC inhibitors.

89. The method of any one of claims 6 to 13, wherein the anti-cancer therapy comprises administering, alone or in combination, one or more cancer vaccines optionally based on cancer-associated tumor antigens, or neo-antigens.

90. The method of claim 2, wherein one or more of the one or more peptide antigens are linked to a targeting antibody, antibody fragment or nanobody that is internalized by the target cell.

91. The method of any one of claims 1 to 77, wherein pre-existing T cell memory is measured prior to the administering of (b).

92. The method of any one of claims 1 to 78, and 91, wherein a few days to weeks prior to the administering of (b), the method comprises boosting immune memory in the subject by administering a vaccine or antigen that stimulates a recall immune response against the one or more peptide antigens.

93. The method of any one of claims 1 to 78 and 91 or 92, wherein recall and targeting of a pre-existing immune response (CD8/CD4) from childhood vaccines leads to tumor cell killing and optionally a subsequent 'abscopal' effect with systemic, cancer-specific immune responses.

94. The method of any one of claims 2 to 78, and 91 to 93, wherein the one or more peptide antigens comprise full antigens or complete proteins derived from the pathogens.