The intensity of antitumor immune responses to immunization with Multivac vaccines against 4T1 carcinoma in BALB/c mice and B16 melanoma in C57BL/6J mice does not depend on the host genotype and the tissue origin of the tumor

Abstract

Introduction. Previously, we reported on the new Multivac methodological platform for the development of personalized antitumor vaccines. The strength of immune response depends on the major histocompatibility complex genes and their products presented on the surface of antigen-presenting cells. The nature of antigens and their diversity in the vaccine composition can also strongly influence the intensity of the immune response during vaccination. Antitumor vaccines of the Multivac series, prepared from tumor tissue or malignant tumor cells, contain a large collection of tumor antigens. This suggests that such vaccines will induce intense immune responses and immune memory, regardless of the genotype of the individual and the tissue nature of the tumor.

Aim. In this work we compared the immunogenicity of the Multivac vaccines against two significantly different tumors (mammary gland carcinoma and melanoma) in two inbred mouse strains that differ significantly in their genetic basis and the genes of the major histocompatibility complex, on which the intensity of adaptive immune responses critically depends.

Material and methods. The multi-antigenic vaccines Multivac-1 were prepared from solid 4T1 mammary carcinoma tissue of BALB/c mice (H-2d genotype) or B16F10 melanoma tissue of C57BL/6J mice (H-2b genotype). Multivac-4 vaccines were based on lysates of malignant cells of 4T1-carcinoma or melanoma B16F10 grown under in vitro cell culture conditions. Multi-antigenic lysates of tumor tissue or malignant cells were supplemented with molecular immunoadjuvants from the class of PRR agonists. Systemic immune responses against 4T1 carcinoma and B16F10 melanoma antigens were determined according to the numbers of antitumor T cells in the spleen and the levels of tumor-specific antibodies in the blood serum of mice. Antigen-reactive CD4 and CD8 T memory cells, and T effector cells secreting interferon-γ were analyzed by ELISpot. Antibodies to intracellular antigens of 4T1-carcinoma and B16F10-melanoma were studied by ELISA.

Results. Both BALB/c and C57BL/6J mouse strains responded effectively to immunization with the Multivac-1 vaccine prepared from 4T1 and B16F10 tumor tissues respectively. More than 1000 CD4+ T effector cells, CD4+ T memory cells, CD8+ T memory cells (per 1 million corresponding T cells) were recorded in the spleens of immunized mice. Even more intense immune responses developed in the spleens of BALB/c and C57BL/6J mice immunized with the Multivac-4 vaccine. Vaccination with Multivac-4 caused an intense accumulation of antigen-reactive T cells memory in mice of both genotypes. Immunization of BALB/c against 4T1-carcinoma and C57BL/6J mice against B16F10-melanoma with vaccines of the Multivac series induced the accumulation in blood serum of a large amounts of antitumor antibodies binding antigens of 4T1 carcinoma and B16F10 melanoma cells.

Conclusion. Multivac vaccines based on multi-antigen lysates of tumor tissue or malignant cells of 4T1 carcinoma or B16F10 melanoma demonstrated equally high immunogenicity. The intensity of immune reactions in response to immunization with the Multivac vaccines did not depend on the genotype of the vaccine recipients. BALB/c and C57BL/6J mice exhibited equally high levels of T-cell and antibody responses to the tumor antigens used in the respective vaccines.

Keywords:antitumor therapeutic vaccine; T-cell reactions; antibodies to tumor antigens; the genotype of the vaccine recipient; tissue nature of the tumor

For citation: Ushakova E.I., Pichugin A.V., Fedorova A.A., Lebedeva E.S., Ataullakhanov R.I. The intensity of antitumor immune responses to immunization with Multivac vaccines against 4T1 carcinoma in BALB/c mice and B16 melanoma in C57BL/6J mice does not depend on the host genotype and the tissue nature of the tumor. Immunologiya. 2022; 43 (6): 691–701. DOI: https://doi.org/10.33029/0206-4952-2022-43-6-691-701 (in Russian).

Funding. This study was supported by a grant from the Russian Science Foundation (project No. 20-15-00391).

Conflict of interests. The authors declare no conflict of interests.

Authors’ contribution. Conducting experiments, statistical processing, editing the article – Ushakova E.I.; planning and conductiong experiments, data analysis – Pichugin A.V.; conducting experiments – Fedorova A.A.; vaccine design, data analysis, article editing – Lebedeva E.S.; concept, design of experiments, data analysis, article writing – Ataullakhanov R.I.

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