Xenogenic testicular antigens for induction of antitumor response

The issues of effective treatment of malignancies are, mainly, related to the problems of tumor cell recognizing, which have only minor differences from healthy cells. A search for treatment approaches based on stimulation of tumor cell recognition by the host immune cells is one of the main tasks of oncoimmunology. The differentiation-related testicular antigens (TAG) in healthy adults are expressed only in testicular cells, being, however, specific markers of tumors of various origins. They play an important role in maintenance of high growth rates and invasive activity of tumor cells. DNA, mRNA and peptide vaccines are currently being developed to induce specific antitumor reactions and generate tumor-specific TAGs in vivo. Xenogeneic variant of TAG, if applied as a vaccine, may enhance immunogenicity of the cell material and is aimed at forming an effector link of immunity, being oriented on TAGs present on the host tumor cells. In our study, a xenogeneic variant of TAG was used to induce antitumor reactions and to enhance immunogenicity. Purpose of the present work was to evaluate the effectiveness of induction of antitumor response in mice having been preliminary immunized with sheep TAGs. In this study, a xenogeneic variant of TAG was used to enhance immunogenicity and induce antitumor response. The survival rate of mice was evaluated using the Kaplan–Meier method. Production of IFNg and IL-10 was assayed by ELISA technique. Phenotyping of CD4⁺CD25⁺FoxP3⁺ and CD4⁺CD44⁺CD62L⁺ cells was performed by multicolor flow cytometry, as well as counting the number of lymphocytes containing intracellular Perforin. Survival rate of mice with preceding TAG vaccination proved to be significantly higher than the parameters obtained with syngeneic TAG vaccination, whereas in some animals a tumor did not grow at all. There was a significant increase in the number of cells carrying Perforins (both CD3⁺ and CD8⁺) during xenogenic vaccination and an increased level of IFNg in serum of LLC tumorbearing mice, while the number of CD4⁺CD25⁺FoxP3⁺T regulatory cells, on the contrary, decreased. Using of xenogenic TAG for immunization has shown that induced immune reactions are directed not only at injected antigens, but also, in a cross-sectional manner, at tumor cells present in a body if they carry any TAGs on their surface. Preliminary immunization with xenogenic TAGs leads to increased life expectancy of mice carrying LLC carcinoma, being accompanied by induction of protective antitumor response directed, in a crosssectional manner, against the own tumor-associated antigens.

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