IMMUNOTHERAPY WITH LOW-DOSE INTERLEUKIN-2 AND ANTI-TRANSFORMING GROWTH-FACTOR-BETA ANTIBODY IN A MURINE TUMOR-MODEL

The purpose of the present study was to evaluate the therapeutic effic acy of low-dose interleukin-2 (IL-2) alone or together with antibody a gainst transforming growth factor-beta (TGF-beta) in a Herpes simplex virus Type 2-transformed (H238) fibrosarcoma model. BALB/c mice were i noculated subcutaneously (s.c.) with 5 x 10(5) H238 tumor cells in one or both hind thighs and treated with IL-2, anti-TGF-beta, or a combin ation of both agents. Nontreated tumor-bearing and normal animals serv ed as controls. In the appropriate treatment groups, each mouse was gi ven a total of 10(5) international units (i.u.) of IL-2 s.c. at one tu mor implantation site and/or 1 mug of anti-TGF-beta intraperitoneally (i.p.) over a period of 5 days beginning on the day of tumor cell impl antation. No toxicity was noted during treatment. The slowest tumor gr owth was observed in mice with single tumors when treated with IL-2 or anti-TGF-beta alone, whereas combination treatment resulted in growth similar to that of untreated controls. However, in animals with two t umors, the tumor injected with IL-2 grew more rapidly than the untreat ed one. Spleen cell responsiveness to mitogenic stimulation was genera lly depressed in tumor-bearing mice compared to normal controls, but s ome differences were noted with treatment. In contrast, tumor presence induced striking splenomegaly and enhanced the chemiluminescent oxida tive burst of phagocytic cells in the spleen. In the groups with a sin gle tumor, plasma TGF-beta levels were similar to those of nontumor-be aring controls, however the concentrations were decreased in the anima ls with two tumors. These results show that IL-2 or anti-TGF-beta can slow progression of H238 tumors under certain conditions. However, com bination of the two modalities proved to be of no benefit.