[Immunotherapy of malignant lymphoma with interleukin-2 and sizofiran--a basic study on EL-4 lymphoma-transplanted mice].

The anti-tumor effects of recombinant human interleukin-2 (rIL-2) and sizofiran (SPG) were evaluated individually and in combination in C57BL/6 mice intraperitoneally inoculated with EL-4 lymphoma. The anti-tumor effects were evaluated by analysis of the intraperitoneal cell population in Giemsa-stained specimens, surface marker analysis of peritoneal exudative cells with flow cytometry, cytotoxic assay of cells against autologous tumor and Yac-1 lymphoma and a negative selection method, to identify the anti-tumor effector cells showing cytotoxic activity. The administration of SPG and/or rIL-2 reduced the lymphoma cells and proliferating lymphocytes, resulting in a decreased tumor/lymphocyte ratio in the order:control mice > SPG-treated mice > rIL-2-treated mice > rIL-2 plus SPG-treated mice. On day 5 after tumor inoculation, elevations in the number of L3T4+, Lyt2+, asialo GM1+ or Mac-1+ were demonstrated in the order:control mice < SPG-treated mice < rIL-2-treated mice < rIL -2 plus SPG-treated mice. The cytotoxic activity of peritoneal exudative cells against autologous tumor and the NK (natural killer) activity were increased in the same order. The anti-tumor effector cells which showed cytotoxic activity against autologous tumor cells were cytotoxic T lymphocytes, NK cells and cytotoxic macrophages. In the mice treated with SPG and rIL-2 plus SPG, especially, cytotoxic macrophages were shown to be the main anti-tumor effector cells. On day 10 after the inoculation, both a marked reduction in Lyt2+ lymphocytes and an elevation of L3T4+ lymphocytes were observed in all groups of mice. NK cells and cytotoxic macrophages were thought to be the main effector cells against autologous tumor, but their cytotoxic activities were lower than those examined on day 5. It was demonstrated that the administration of SPG and/or rIL-2 to the EL-4 lymphoma-bearing mice activated immune response cells in the peritoneal cavity such as T lymphocytes, NK cells or macrophages, which caused a reduction in lymphoma cells. The combination rIL-2 and SPG therapy was shown to activate the anti-tumor immune response at the tumor site more effectively than when either agent was administered alone.