EVALUATION OF THE ANTITUMOR EFFICACY OF SYNTHETIC NEOANTIGEN PEPTIDES FOR THE MELANOMA VACCINE MODEL

Introduction. Personalized vaccine therapy that stimulates immune system to recognize mutant tumor neoantigens is one of the promising approaches of cancer treatment.

Objective. Evaluation of immunogenicity and antitumor efficacy of synthetic neoantigen peptides and poly(I:C) adjuvant against murine melanoma B16F10.

Materials and methods. 43 synthetic mutant neoantigen peptides selected earlier according to the bioinformatics analysis of the results of melanoma B16F10 sequencing were investigated. The study was performed in mice C57Bl / 6J with subcutaneously transplanted melanoma B16F10 after double vaccination by peptide groups with or without adjuvant poly(I:C). Immunogenicity of peptides was evaluated by ELISPOT that detected the number of interferon-gamma producing cells. Antitumor activity was evaluated on the base of tumor growth inhibition and the increase of the survival rate.

Results. The number of interferon-gamma producing cells increased after in vitro stimulation by the peptides of the model vaccine in the group of mice which had been vaccinated by these peptides with the adjuvant. The number of interferon-gamma producing cells in vitro did not change after addition of vaccine peptides or any other peptides in the groups of mice that had been vaccinated by the peptides without the adjuvant as compared to the control group. Double vaccination by the peptides with the adjuvant induced a potent antitumor effect in some cases, three of the eight groups of the peptides with the adjuvant induced significant inhibition of tumor growth and the increase of survival rate in mice.

Conclusion. Thereby, it was shown that vaccination of mice by peptides in combination with adjuvant poly(I:C) stimulated the cell immunity response, however, the increase of the number of interferon-gamma producing cells is not an indicator of the antitumor efficacy of neoantigen peptides.

1. Baryshnikova M.A., Kosobokova E.N., Kosorukov V.S. Neoantigens in tumor immunotherapy Rossiysky bioterapevtichesky zhurnal = Russian Journal of Biotherapy 2018;17(2):6–14. (In Russ.) DOI: 10.17650/1726-9784-2018-17-2-6-14.

2. Castle J.C., Kreiter S., Diekmann J. et al. Exploiting the mutanome for tumor vaccinatio n. Cancer Res 2012;72(5):1081–90. DOI: 10.1158/0008-5472.CAN-11-3722.

3. Ott P.A., Hu Z., Keskin D.B. et al. An immunogenic personal neoantigen vaccine for patients with melanoma. Nature 2017;547(7662):217–21. DOI: 10.1038/nature22991.

4. Kosorukov V.S., Baryshnikova M.A., Kosobokova E.N. et al. Identification of immunogenic mutant neoantigens in the genome of murine melanoma Rossiysky bioterapevtichesky zhurnal = Russian Journal of Biotherapy 2019;18(3):23–30. (In Russ.) DOI: 10.17650/1726-9784-2019-18-3-23-30.