Background Personalized tumor vaccines based on synthetic peptide neoantigens or those encoded in RNA-vector are successfully studied in phase 1 and 2 clinical trials in melanoma and glioblastoma patients.
Objectives In our study we compare immunogenicity of two personalized tumor vaccine platforms, one based on DNA-vector encoding tumor neoantigens and the other multiantigenic vaccine made of primary tumor tissue with included molecular immunoadjuvants.
Materials and Methods As a neo-antigenic tumor vaccine (Ad-B16) the recombinant adenovirus vector, encoding B16F10 melanoma mutant antigen, was used. A multi-antigenic tumor vaccine (MTV-B16) was made out of the B16F10 tumor tissue. PRR-agonistic molecular immunoadjuvants were included in the multiantigenic B16 tumor tissue-derived vaccine in order to activate antigen-presenting dendritic cells and reprogram myeloid suppressors. The number of antigen-reactive IFNγ-secretory T effector and T effector memory cells was analyzed by ELISPOT. Serum antibodies specific to intracellular antigens of B16F10 melanoma cells were analyzed using ELISA, while FACS was applied to detect B16F10 surface antigens.
Results MTV-B16 vaccine show stronger immunogenicity than Ad-B16 as to generation of tumor-specific IFNγ-secretory T cells in the spleen of mice. After immunization with MTV-B16, up to 6500 IFNγ CD4 and 3500 IFNγ CD8 T-effector cells (per 1 mln T cells) were discovered versus 600 IFNγ CD4 and 650 IFNγ CD8 T-effector cells generated by Ad-B16. Both vaccines induced serum antibodies specifically recognizing B16F10 melanoma’s intracellular and cell surface antigens.
Conclusions A personalized multi-antigen tumor vaccine MTV-B16, made out of tumor tissue and completed with molecular adjuvants, induces siginificantly stronger tumor-specific Th1-type CD4 and CD8 T cell responses than those generated by the neoantigen Ad-B16 vaccine on the adenovirus vector platform.
Funding This study was supported by the Russian Science Foundation (project №20-15-00391).
Disclosure Information E. Ushakova: None. A. Fedorova: None. E. Lebedeva: None. A. Pichugin: None. R. Ataullakhanov: None.
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