IMMUNOTHERAPY WITH LOW-DOSE INTERLEUKIN-2 AND INTERFERON-GAMMA IN A MURINE TUMOR-MODEL

The aim of this study was to evaluate the therapeutic efficacy of loca lly administered low-dose interleukin-2 (IL-2) alone or together with interferon-gamma (IFN-gamma) in a herpes simplex virus type 2-transfor med murine (H238) fibrosarcoma model. In vitro incubation showed that IL-2, but not IFN-gamma, had a significant inhibitory effect on DNA sy nthesis in H238 cells, In vivo experiments were performed with BALB/c mice to determine the optimal time of treatment with each cytokine aft er subcutaneous (sc) tumor implantation, The greatest antitumor effect with IL-2 (1 x 10(5) total international units, sc) was noted when tr eatment was administered during the first week after tumor injection, whereas with IFN-gamma (500 total units, intraperitoneally) treatment during the second week proved best, Combination of the two agents prod uced complete tumor regression in 44.4% of mice; regression with singl e-modality treatment was 0-11%, The presence of H238 tumor induced spl enomegaly and enhanced the oxidative burst capacity of phagocytes, Per ipheral blood leukocyte counts were low in tumor-bearing groups, regar dless of treatment, IL-2 and IFN-gamma were nondetectable in the plasm a of tumor-bearing or control mice; however, total TGF-beta(1) was 248 % higher with IL-2 treatment compared with tumor-bearing nontreated co ntrols. These results show that IL-2 and IFN-gamma can significantly i nhibit the growth of highly aggressive H238 tumors and support further investigations with these agents.