ADVANCED METHODS OF EXPERIMENTAL CANCER IMMUNOTHERAPY BASED ON THE DELAYED-TYPE HYPERSENSITIVITY

Abstract

Introduction. Among the variety forms of inflammation, many of which contribute to the growth of tumors, classical inflammation reaction - delayed type hypersensitivity is able to eliminate. Artificially induced intratumoral it can be used successfully in immunotherapy. As the level of antitumor immunity correlates with the intensity of the reaction, we used the results of our preliminary research, which helped to increase the level of delayed type hypersensitivity several times. 0ur earlier experiments indicated a paradoxical mechanism of bi-directional control of delayed type hypersensitivity reactions at various stages by antigens class IIMHC I-A-molecules, expressed on the surface of antigen-presenting cells. This fact must be strictly taken into account when designing schemes of immunotherapy. The purpose of the research is development of effective methods for experimental immunotherapy on the basis of delayed type hypersensitivity with the use of means and methods of its regulation. Materials and methods. The above-described phenomenon was used in the development of 2 methods experimental immunotherapy of carcinoma Lewis in mice BDF1. Delayed type hypersensitivity to laboratory antigen ovalbumin induced intratumoral and stimulated point based bi-directional development of reaction or aspirin in the induction stage (indirectly increasing the expression of I-A-anti-gens), or (overpowering her) nicotinamide in the effector phase of the reaction. Results. It is shown that delayed type hypersensitivity to ovalbumin induced intratumoral and stimulated by aspirin or nicotinamide, provides inhibition of tumor growth at 81.5 % and 86.5 % compared with the control, respectively. Conclusion. It is demonstrated 2 ways of experimental immunotherapy of tumors based on delayed type hypersensitivity, with strict regard to bi-directional control reaction by I-a-antigens. According to the literature in a number of agents capable of altering the expression of I-A-molecules, in addition to aspirin and nicotinamide are a well known, widely used in the clinic drugs. The irregularity of bi-directional development of delayed type hypersensitivity during their appointment subsequently leads not only to the weak therapeutic effect, but may cause increased tumor growth. Probably this is the reason for the observed unpredictability in immunotherapy. Obviously, to develop appropriate treatment regimens need careful, targeted intervention in the specific protective immune response in accordance with its molecular mechanism of regulation. In summary, the results presented here can be the basis for the testing of these methodological approaches in the clinic.