The use of xenogenic testicular antigens for induction of antitumor reactions

Abstract

Testicular antigens (TAGs) are normally expressed only by cells of testicular and placental tissues. Human immune system is tolerant to TAG, but if the integrity of the testicular membranes is disrupted, these antigens, entering the bloodstream, induce autoimmune reactions for eliminating them from the body. In malignancy, TAGs begin to be expressed by tumor cells of the liver, breast, pancreas, intestine, and lung. Immunological recognition of these AGs leads to autoimmune reactions against these AGs, i.e. antitumor reactions in the body. We used xenogenic TAGs derived from ram testis to increase TAG immunogenicity. The use of ram TAGs is justified by the fact that TAGs are evolutionarily conserved molecules and there is a high degree of homology between human and animal TAGs.The purpose of the study was to evaluate the lifespan of tumor-bearing mice and parameters of cellular immunity in various options for immunizing mice with ram TAGs.Material and Methods. C57BL/6 mice were used. The efficacy of therapeutic or prophylactic vaccination with xenogenic TAGs was studied by changing lifespan of B16 and LLC tumor-bearing mice. Formation of immune responses was evaluated by proliferative ability of splenocytes to respond to vaccination and control AGs and by their production of IFN-gamma and IL-10.Results. In the LLC carcinoma model with a preventive vaccination option, the lifespan of mice with syngeneic vaccination did not differ from the tumor control; the lifespan of mice with xenogeneic vaccination increased by 60%. In therapeutic vaccination option, no significant differences in lifespan of vaccinated mice were found. A significant increase in the proliferative activity of splenocytes in response to tumor AGs was found in both LLC- and B16 tumor-bearing mice previously vaccinated with xenogenic TAGs. The increased IFN-gamma production by splenocytes was observed in B16 and LLC tumorbearing mice with xenogeneic vaccination. The IFN-gamma production by splenocytes in tumor-bearing mice with syngeneic vaccination was not increased. A significant decrease in IL-10 production was noted in mice with xenogeneic vaccination.