Effect of some cytokine combinations on growth and metastasis of experimental melanoma.

Abstract

e21081 Background: The purpose of the study was development and experimental validation of new methods of melanoma immunotherapy involving cytokines. Methods: The study included 30 С57Bl/6 mice with transplantable B16 melanoma. Dynamics of tumor growth, melanoma metastases to the lungs and spleen, morphology of melanoma, spleen and thymus and lymphocyte subsets in the blood and spleen after injected combinations of immunomodulators based on recombinant cytokines – IL-2 (Roncoleukin), IFN-γ (Ingaron) and TNF-α with thymosin (Refnot) – were studied. Results: Roncoleukin+Ingaron was the most effective combination that inhibited tumor growth during the therapy and after it by 30-38% and had a marked antimetastatic effect, up to complete absence of metastases in all animals. Morphological study demonstrated that thymus was the most active in this group of mice (a well-developed cortex with densely packed thymocytes); apparently, it was the cause for the increased levels of T-cells in the blood and Th (CD3e+CD4+) in the spleen of tumor-bearing mice compared to controls. The spleen of the mice showed a well-developed white pulp with large follicles, and Th level was the maximal – 47.9±1.5%, while in other groups it ranged from 15 to 35%. Morphological study of tumors revealed extensive necrosis (up to 2/3 of the tumor area), leukocyte infiltration, bleeds, blood clots in the vessel lumen and degenerative changes in tumor cells in all combinations of immunomodulators. Melanoma structure in the control group was typical, and most mice developed small and large metastases, sometimes multiple ones with extensive lung lesions; spleen metastases were observed in some mice. Conclusions: The study demonstrated the benefits of a search for optimal combinations of cytokine-based immune drugs to influence effectively an experimental transplantable tumor.