Xenogeneic cell-based vaccine therapy for stage III melanoma: safety, immune-mediated responses and survival benefits

Селедцова, Г. В.; Shishkov, Alexey A.; Kaschenko, E. A.; Гончаров, А. Г.; Газатова, Н. Д.; Селедцов, В. И.

doi:10.1684/ejd.2016.2733

Cited by 8 publications

(3 citation statements)

References 11 publications

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“…Similar efforts are being made to increase the affinity of the MHC/peptide complex to T cell receptors [ 80 ]. The latest approach to increase antigen presentation is the use of xenogenic antigens [ 81 ]. This approach was very successful in the development of the USDA-approved DNA vaccine against canine melanoma.…”

Section: Optimization Of Dna Vaccinesmentioning

confidence: 99%

DNA Vaccines—How Far From Clinical Use?

Hobernik

Bros

2018

IJMS

388

332

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Two decades ago successful transfection of antigen presenting cells (APC) in vivo was demonstrated which resulted in the induction of primary adaptive immune responses. Due to the good biocompatibility of plasmid DNA, their cost-efficient production and long shelf life, many researchers aimed to develop DNA vaccine-based immunotherapeutic strategies for treatment of infections and cancer, but also autoimmune diseases and allergies. This review aims to summarize our current knowledge on the course of action of DNA vaccines, and which factors are responsible for the poor immunogenicity in human so far. Important optimization steps that improve DNA transfection efficiency comprise the introduction of DNA-complexing nano-carriers aimed to prevent extracellular DNA degradation, enabling APC targeting, and enhanced endo/lysosomal escape of DNA. Attachment of virus-derived nuclear localization sequences facilitates nuclear entry of DNA. Improvements in DNA vaccine design include the use of APC-specific promotors for transcriptional targeting, the arrangement of multiple antigen sequences, the co-delivery of molecular adjuvants to prevent tolerance induction, and strategies to circumvent potential inhibitory effects of the vector backbone. Successful clinical use of DNA vaccines may require combined employment of all of these parameters, and combination treatment with additional drugs.

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Section: Optimization Of Dna Vaccinesmentioning

confidence: 99%

DNA Vaccines—How Far From Clinical Use?

Hobernik

Bros

2018

IJMS

388

332

View full text Add to dashboard Cite

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“…Moreover, antigens with a prolonged half-life have been shown to induce stronger CTL responses, and thereby increased immunogenicity [ 80 ]. To improve the presentation of (tumor) antigens, epitope-specific changes have been shown to increase MHC affinity [ 81 ], including the use of xenogeneic antigens [ 82 ]. Loading of pDNA-encoded antigens onto MHCII was also demonstrated to be improved by inclusion of the coding sequence of the invariant chain [ 83 ].…”

Section: Nucleic Acid-based Strategies To Induce Adaptive Anti-tummentioning

confidence: 99%

Nucleic Acid-Based Approaches for Tumor Therapy

Hager

Fittler

Wagner

et al. 2020

Cells

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Within the last decade, the introduction of checkpoint inhibitors proposed to boost the patients’ anti-tumor immune response has proven the efficacy of immunotherapeutic approaches for tumor therapy. Furthermore, especially in the context of the development of biocompatible, cell type targeting nano-carriers, nucleic acid-based drugs aimed to initiate and to enhance anti-tumor responses have come of age. This review intends to provide a comprehensive overview of the current state of the therapeutic use of nucleic acids for cancer treatment on various levels, comprising (i) mRNA and DNA-based vaccines to be expressed by antigen presenting cells evoking sustained anti-tumor T cell responses, (ii) molecular adjuvants, (iii) strategies to inhibit/reprogram tumor-induced regulatory immune cells e.g., by RNA interference (RNAi), (iv) genetically tailored T cells and natural killer cells to directly recognize tumor antigens, and (v) killing of tumor cells, and reprograming of constituents of the tumor microenvironment by gene transfer and RNAi. Aside from further improvements of individual nucleic acid-based drugs, the major perspective for successful cancer therapy will be combination treatments employing conventional regimens as well as immunotherapeutics like checkpoint inhibitors and nucleic acid-based drugs, each acting on several levels to adequately counter-act tumor immune evasion.

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“…Allogeneic tumor cell vaccines are typically prepared from two or three established human tumour cell lines [3]. Finally, to our knowledge, xenogeneic cellbased vaccines could constitute the most effective approach to stimulate antitumor immune responses in clinical cancer settings [11,12]. This opinion is substantiated by observations that xenogeneic proteins are highly immunogenic and effective in breaking immune tolerance to human analogs.…”

Section: Introductionmentioning

confidence: 99%

Efficiency of the Formation of Antitumor Immune Responses in the System of Preventive Vaccination of Mice With Testicular Antigens

et al. 2021

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Аppearance of a malignant tumor is associated with impaired mechanisms of proliferation, differentiation, apoptosis ability. However, these changes are not enough for immune system to recognize and destroy mutated cells. Weak immunogenicity of tumor-associated antigens (TAA) and the insufficiency of co-stimulating molecules on the surface of tumor cells is a reason for this phenomenon Since biochemical processes of tumor cells and healthy tissue cells are identical, therefore creation of effective chemotherapeutic drugs is limited not by selectivity of their action. So antitumor vaccination is the most effective specific method for both preventing recurrence of a disease and a therapeutic treatment tool in oncology. Xenogeneic proteins are highly immunogenic and effective in breaking immune tolerance to human analogs. In our work, we used sheep testicular AG as a source xenogenic TAAs. Sheep testicles contain a large set of TAAs. Experimental mice were immunized with type liposomal testicular vaccine from sheep, one month after vaccination, to induce tumor growth, cells of carcinoma LLC were implanted in mouse. The life expectancy of the experimental group of mice was 2 times higher compared to the syngenetic control and 20% of them did not develop the tumor at all. In the spleen of mice who did not have tumors after pre-vaccination sheep liposomal testicular AG, T-regulatory cells and T-memory cells were measured. We found a credible decrease in both naive Treg (CD4+CD25+), activated (CD4+CD25+FoxP3+) and both T-memory (CD4+CD44+) and central memory (CD4+CD44+CD62L+) in spleen pre-vaccination mice with compared to the contral intact spleen. Content of IFNg and IL-10 in supernatants of mouse slenocytes derived from vaccinated mice with no tumors was investigated and showed a reliable decrease in the amount of IL-10, but not IFNg. We believe that immunization with xenogenic tumor AGs can lead to the formation of a protective antitumor response.

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Xenogeneic cell-based vaccine therapy for stage III melanoma: safety, immune-mediated responses and survival benefits

Cited by 8 publications

References 11 publications

DNA Vaccines—How Far From Clinical Use?

DNA Vaccines—How Far From Clinical Use?

Nucleic Acid-Based Approaches for Tumor Therapy

Efficiency of the Formation of Antitumor Immune Responses in the System of Preventive Vaccination of Mice With Testicular Antigens

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