Combined Application of Anticancer Vaccines of IEPOR Series and Doxorubicin in Rats with Transplanted Walker Carcinosarcoma

Anticancer xenogeneic vaccine – is an agent, containing antigens of embryonic origin that underwent biotransformation under the action of cytotoxic proteins of В. subtilis B-7025. Anticancer efficacy of the vaccine is implemented by breaking immune system tolerance to own tumor antigens due to the antigenic similarity between tumor and embryonic proteins. The experiments were conducted in Wistar female rats (age 2.5 months and weight 200-220 g, bred at the animal house of R. E. Kavetsky Institute of Experimental Pathology, Oncology and Radiobiology). The care and use of the experimental animals have been performed in accordance with generally accepted international rules for conducting experiments in experimental animals. As an experimental tumor model, we have used Walker carcinosarcoma. In preclinical and clinical trials, success has been demonstrated in the use of a combination of anticancer vaccines with chemotherapy to achieve a synergistic effect, even if the dose and schedule of administration of the agents needed to be optimized. It has been shown that some drugs (doxorubicin, cyclophosphamide, docetaxel) induce immunological death of tumor cells, increase the expression of tumor-associated antigens, HLA-peptide complexes, thus sensitizing the tumor in vaccine-induced T-cell killing. It was determined that simultaneous administration of anticancer vaccines (regardless of the antigenic composition) and Doxorubicin resulted in a significant increase of survival and average lifespan of the experimental animals. The treated animals at the end of the experiment presented with increased cytotoxicity of lymphocytes and macrophages (both direct and antibody-dependent), suggesting a reduced level of immunosuppression in experimental animals. In the group of rats, receiving Dox, the serum had no effect on the activity of lymphocytes. These data suggest that during the development of tumor the serum accumulates humoral factors, capable of blocking lymphocyte activity. Yet, as a result of additional activation (due to anticancer vaccines), the conditions are provided when the inhibitory activity of humoral factors is eliminated. The combined application of chemo- and biotherapy based on anticancer vaccines of IEPOR series is an efficient and rather perspective method of inhibition of malignant tumor process. The optimal scheme of the combined therapy was developed that involved the administration of anticancer vaccines together with the application of chemotherapeutic agents. The augmentation of antitumor effect can be explained by the reduction of immunosuppressive activity of blood serum towards the effector cells of antitumor immunity, resulting from the additional signal to the immune system - use of anticancer vaccines.