EVALUATION OF IMMUNOGENICITY OF SYNTHETIC NEOANTIGEN PEPTIDES FOR THE MELANOMA VACCINE MODEL

Abstract

Introduction. Immunotherapy based on the usage of mutant tumor neoantigens to activate the antitumor immune response is one of the most promising approaches to cancer treatment.Purpose. Evaluation of individual immunogenicity of synthetic neoantigen peptides for the B16-F10 melanoma vaccine model.Materials and methods. We studied 32 synthetic neoantigen peptides with a length of 25–27 amino acids, which were previously selected as potentially immunogenic by bioinformatic analysis of B16-F10 melanoma sequencing data and healthy tissues of C57Bl/6J mice. Groups of C57Bl/6J mice were immunized four times at weekly intervals with each individual peptide in combination with the adjuvant Poly(I:C), one of the groups was immunized only with Poly(I:C), and the control group was not immunized with anything. The immunogenicity of peptides was assessed by the production of interferon γ in splenocytes using the ELISpot method and by the level of serum cytokines Th1/Th2 using the ELISA method in immunized mice and in animals in the control group.Results. Of the 32 peptides studied, 25 caused an increase in the number of interferon-γ-producing spleen cells in previously immunized mice, but 8 of these peptides caused a non-specific increase in the production of interferon γ by splenocytes in non-immunized animals. It was found that out of 32 peptides, only 11 caused an increase in the level of serum cytokines interferon γ and interleukin 4, which are responsible for the development of the immune response along the Th1 and Th2 pathways. But only 7 peptides affected an increase in the number of interferon-γ-producing splenocytes and an enhance of cytokines interferon γ and interleukin 4 levels.Conclusion. Thus, the immunogenicity of 32 synthetic neoantigen peptides was evaluated, and 7 peptides were shown to activate the cellular immune response.