[go: up one dir, main page]
More Web Proxy on the site http://driver.im/
Next Issue
Volume 4, September
Previous Issue
Volume 4, March
You seem to have javascript disabled. Please note that many of the page functionalities won't work as expected without javascript enabled.
 
 
Search for Articles:
Title / Keyword
Author / Affiliation / Email
Journal
Article Type
 
 
Advanced Search
 
Section
Special Issue
Volume
Issue
Number
Page
 
5.2
3.9
Journals
Biomedicines
Volume 4
Issue 2
share announcement

Biomedicines, Volume 4, Issue 2 (June 2016) – 5 articles

  • Issues are regarded as officially published after their release is announced to the table of contents alert mailing list.
  • You may sign up for e-mail alerts to receive table of contents of newly released issues.
  • PDF is the official format for papers published in both, html and pdf forms. To view the papers in pdf format, click on the "PDF Full-text" link, and use the free Adobe Reader to open them.
Order results
Result details
Section
Show export options expand_more Show export options expand_less
Select all
Export citation of selected articles as:
617 KiB  
Review
Plant Toxin-Based Immunotoxins for Cancer Therapy: A Short Overview
by Letizia Polito, Alice Djemil and Massimo Bortolotti
Biomedicines 2016, 4(2), 12; https://doi.org/10.3390/biomedicines4020012 - 1 Jun 2016
Cited by 64 | Viewed by 9333
Abstract
Immunotoxins are chimeric proteins obtained by linking a toxin to either an intact antibody or an antibody fragment. Conjugation can be obtained by chemical or genetic engineering, where the latter yields recombinant conjugates. An essential requirement is that the target molecule recognized by [...] Read more.
Immunotoxins are chimeric proteins obtained by linking a toxin to either an intact antibody or an antibody fragment. Conjugation can be obtained by chemical or genetic engineering, where the latter yields recombinant conjugates. An essential requirement is that the target molecule recognized by the antibody is confined to the cell population to be deleted, or at least that it is not present on stem cells or other cell types essential for the organism’s survival. Hundreds of different studies have demonstrated the potential for applying immunotoxins to many models in pre-clinical studies and in clinical trials. Immunotoxins can be theoretically used to eliminate any unwanted cell responsible for a pathological condition. The best results have been obtained in cancer therapy, especially in hematological malignancies. Among plant toxins, the most frequently employed to generate immunotoxins are ribosome-inactivating proteins, the most common being ricin. This review summarizes the various approaches and results obtained in the last four decades by researchers in the field of plant toxin-based immunotoxins for cancer therapy. Full article
(This article belongs to the Special Issue Development, Manufacture and Clinical Application of Drug Conjugates in Cancer Therapy)
►▼ Show Figures

Graphical abstract

Graphical abstract
Full article ">Figure 1
<p>Plant toxin-based immunotoxins (type 1 RIPs or type 2 RIP A chains) can cause cell death by triggering multiple death pathways. Once the toxin reaches the cytosol, endoplasmic reticulum or nucleus, it can cause apoptosis activation, necroptosis, oxidative stress, the inhibition of protein synthesis and probably autophagy. Also, the antibody can activate cell death through apoptosis or through complement-dependent cytotoxicity (CDC) and antibody-dependent cellular cytotoxicity (ADCC), in the event that whole antibody molecules are used.</p> Full article ">
564 KiB  
Review
Recent Innovations in Peptide Based Targeted Drug Delivery to Cancer Cells
by Yosi Gilad, Michael Firer and Gary Gellerman
Biomedicines 2016, 4(2), 11; https://doi.org/10.3390/biomedicines4020011 - 26 May 2016
Cited by 81 | Viewed by 11295
Abstract
Targeted delivery of chemotherapeutics and diagnostic agents conjugated to carrier ligands has made significant progress in recent years, both in regards to the structural design of the conjugates and their biological effectiveness. The goal of targeting specific cell surface receptors through structural compatibility [...] Read more.
Targeted delivery of chemotherapeutics and diagnostic agents conjugated to carrier ligands has made significant progress in recent years, both in regards to the structural design of the conjugates and their biological effectiveness. The goal of targeting specific cell surface receptors through structural compatibility has encouraged the use of peptides as highly specific carriers as short peptides are usually non-antigenic, are structurally simple and synthetically diverse. Recent years have seen many developments in the field of peptide based drug conjugates (PDCs), particularly for cancer therapy, as their use aims to bypass off-target side-effects, reducing the morbidity common to conventional chemotherapy. However, no PDCs have as yet obtained regulatory approval. In this review, we describe the evolution of the peptide-based strategy for targeted delivery of chemotherapeutics and discuss recent innovations in the arena that should lead in the near future to their clinical application. Full article
(This article belongs to the Special Issue Development, Manufacture and Clinical Application of Drug Conjugates in Cancer Therapy)
►▼ Show Figures

Graphical abstract

Graphical abstract
Full article ">Figure 1
<p>Schematic representation of PDC (peptide based drug conjugate).</p> Full article ">Figure 2
<p>Schematic representation of peptide optimization methodologies.</p> Full article ">
1351 KiB  
Review
Cancer Vaccines in Ovarian Cancer: How Can We Improve?
by Silvia Martin Lluesma, Anita Wolfer, Alexandre Harari and Lana E. Kandalaft
Biomedicines 2016, 4(2), 10; https://doi.org/10.3390/biomedicines4020010 - 3 May 2016
Cited by 49 | Viewed by 9752
Abstract
Epithelial ovarian cancer (EOC) is one important cause of gynecologic cancer-related death. Currently, the mainstay of ovarian cancer treatment consists of cytoreductive surgery and platinum-based chemotherapy (introduced 30 years ago) but, as the disease is usually diagnosed at an advanced stage, its prognosis [...] Read more.
Epithelial ovarian cancer (EOC) is one important cause of gynecologic cancer-related death. Currently, the mainstay of ovarian cancer treatment consists of cytoreductive surgery and platinum-based chemotherapy (introduced 30 years ago) but, as the disease is usually diagnosed at an advanced stage, its prognosis remains very poor. Clearly, there is a critical need for new treatment options, and immunotherapy is one attractive alternative. Prophylactic vaccines for prevention of infectious diseases have led to major achievements, yet therapeutic cancer vaccines have shown consistently low efficacy in the past. However, as they are associated with minimal side effects or invasive procedures, efforts directed to improve their efficacy are being deployed, with Dendritic Cell (DC) vaccination strategies standing as one of the more promising options. On the other hand, recent advances in our understanding of immunological mechanisms have led to the development of successful strategies for the treatment of different cancers, such as immune checkpoint blockade strategies. Combining these strategies with DC vaccination approaches and introducing novel combinatorial designs must also be considered and evaluated. In this review, we will analyze past vaccination methods used in ovarian cancer, and we will provide different suggestions aiming to improve their efficacy in future trials. Full article
(This article belongs to the Special Issue Dendritic Cells and Cancer Immunotherapy)
►▼ Show Figures

Graphical abstract

Graphical abstract
Full article ">Figure 1
<p>Summary of required considerations to implement a successful vaccination strategy in ovarian cancer.</p> Full article ">
995 KiB  
Review
Genetic Modification of T Cells
by Richard A. Morgan and Benjamin Boyerinas
Biomedicines 2016, 4(2), 9; https://doi.org/10.3390/biomedicines4020009 - 20 Apr 2016
Cited by 37 | Viewed by 10924
Abstract
Gene transfer technology and its application to human gene therapy greatly expanded in the last decade. One area of investigation that appears particularly promising is the transfer of new genetic material into T cells for the potential treatment of cancer. Herein, we describe [...] Read more.
Gene transfer technology and its application to human gene therapy greatly expanded in the last decade. One area of investigation that appears particularly promising is the transfer of new genetic material into T cells for the potential treatment of cancer. Herein, we describe several core technologies that now yield high-efficiency gene transfer into primary human T cells. These gene transfer techniques include viral-based gene transfer methods based on modified Retroviridae and non-viral methods such as DNA-based transposons and direct transfer of mRNA by electroporation. Where specific examples are cited, we emphasize the transfer of chimeric antigen receptors (CARs) to T cells, which permits engineered T cells to recognize potential tumor antigens. Full article
(This article belongs to the Section Immunology and Immunotherapy)
►▼ Show Figures

Graphical abstract

Graphical abstract
Full article ">Figure 1
<p>Gamma retroviral vectors. (<b>A</b>) Genomic structure of MLV-derived γ-retroviral vectors. Essential genes <span class="html-italic">gag</span>, <span class="html-italic">pol</span>, and <span class="html-italic">env</span> are removed from the viral backbone and provided in <span class="html-italic">trans</span> for viral production. Transgene encoding CAR is introduced in place of the viral genes<span class="html-italic">.</span> A packaging cell line is transfected with the vector carrying the CAR transgene, packaging and <span class="html-italic">env</span> helper plasmids. If desired, selective antibiotic pressure is utilized to select for plasmid integration and generate stable virus-producing lines for large-scale production. (<b>B</b>) Retroviral particles are collected from the cell culture supernatant and used to transduce stimulated T cells (OKT3/CD28 blasts). After genomic integration, the CAR is stably expressed on the surface of T cells. att, integration signal; E, enhancer; P, promoter; pA, polyadenylation signal; PBS, tRNA primer-binding site; SD, Splice donor; Ψ, encapsidation signal; PPT, polypurine tract.</p> Full article ">Figure 2
<p>Modes of insertional mutagenesis. (<b>A</b>) Promoter insertion—expression of a cellular gene is upregulated when an insertion is upstream and in frame with the cellular ORF (open reading frame). Read-through from either the endogenous promoter or the viral LTR can induce aberrant gene expression. (<b>B</b>) Promoter activation—activity of a cellular promoter is influenced by enhancer elements in the viral LTR. This effect is not dependent on orientation or frame agreement and can function at a distance of several kilobases; (<b>C</b>) intronic insertions can lead to the production of truncated cellular transcripts. Adapted from Suerth <span class="html-italic">et al.</span> [<a href="#B1-biomedicines-04-00009" class="html-bibr">1</a>].</p> Full article ">Figure 3
<p>Lentiviral vectors. Lentivirus based vectors are similar to their retroviral counterparts. A split packaging system is utilized with a packaging cell line to produce viral particles. An accessory plasmid provided in <span class="html-italic">trans</span> unique to lentivirus is <span class="html-italic">rev</span>, which enhances nuclear export of gag-pol transcripts. Another component unique to lentiviral vectors is the central polypurine tract (cPPT), which facilitates nuclear import of the preintegration complex. EP, eukaryotic promoter; RRE, rev response element; cPPT, central polypurine tract; PBS, tRNA primer-binding site; Ψ, encapsidation signal.</p> Full article ">Figure 4
<p>Transposons. Transposons are dual component systems composed of one plasmid carrying the CAR (transposon) and the other carrying the transposase. The transposase acts on the terminal inverted repeats flanking the CAR, which leads to excision and subsequent integration at a TA dinucleotide sequence in the target cell genome. DNA plasmids carrying the CAR (transposon) and transposase are electroporated into PBMCs. Following transposition and stable genomic integration, the CAR protein is expressed on the surface of the T cell. TIR, terminal inverted repeats; P, promoter. Adapted from Cai &amp; Mikkelsen [<a href="#B54-biomedicines-04-00009" class="html-bibr">54</a>].</p> Full article ">
1001 KiB  
Review
Prospects for Foamy Viral Vector Anti-HIV Gene Therapy
by Arun K. Nalla and Grant D. Trobridge
Biomedicines 2016, 4(2), 8; https://doi.org/10.3390/biomedicines4020008 - 29 Mar 2016
Cited by 4 | Viewed by 7449
Abstract
Stem cell gene therapy approaches for Human Immunodeficiency Virus (HIV) infection have been explored in clinical trials and several anti-HIV genes delivered by retroviral vectors were shown to block HIV replication. However, gammaretroviral and lentiviral based retroviral vectors have limitations for delivery of [...] Read more.
Stem cell gene therapy approaches for Human Immunodeficiency Virus (HIV) infection have been explored in clinical trials and several anti-HIV genes delivered by retroviral vectors were shown to block HIV replication. However, gammaretroviral and lentiviral based retroviral vectors have limitations for delivery of anti-HIV genes into hematopoietic stem cells (HSC). Foamy virus vectors have several advantages including efficient delivery of transgenes into HSC in large animal models, and a potentially safer integration profile. This review focuses on novel anti-HIV transgenes and the potential of foamy virus vectors for HSC gene therapy of HIV. Full article
(This article belongs to the Special Issue Gene Therapy Strategies for HIV/AIDS)
►▼ Show Figures

Graphical abstract

Graphical abstract
Full article ">Figure 1
<p>HIV genome and gene therapy approaches targeting viral genes to block replication. Dotted arrows indicate the function of the viral genes and red lines indicate the gene-targeting approaches used to block HIV replication.</p> Full article ">Figure 2
<p>HIV-1 life cycle and host co-factors. HIV exploits several host co-factors for its infection and replication. For entry, HIV uses the host receptor CD4 with the coreceptors CCR5 or CXCR4. Nuclear import and integration of the viral genome is supported by several host co-factors including LEDGF, Importin and TNPO3. Host cell cycle regulators support viral transcription, while proteins like ALIX and Tsg101 aid in budding of HIV virions. In contrast, HIV infection is restricted by several host restriction factors like TRIM5α, SAMHD1, APOBEC3G, Tetherin and MX2. Altering these co-factors and restriction factors by various strategies like siRNA, gene editing, ribozymes, expression of dominant negative variants and host restriction factors can block HIV replication. Numbers represent the steps in HIV life cycle, 1: Entry; 2: Uncoating; 3: Reverse Transcription; 4: Nuclear import; 5: Integration; 6: Transcription; 7: Nuclear export; 8: Translation; 9: Assembly; 10: Budding; and 11: Release and maturation.</p> Full article ">
Show export options expand_more Show export options expand_less
Select all
Export citation of selected articles as:
 
Displaying articles 1-5
Previous Issue
Next Issue
Back to TopTop