IMMUNOTHERAPY WITH LOW-DOSE INTERLEUKIN-2 AND A POLYSACCHAROPEPTIDE DERIVED FROM CORIOLUS-VERSICOLOR

The purpose of the present study was to evaluate the therapeutic effic acy of locally administered low-dose interleukin-2 (IL-2) and a polysa ccharopeptide (PSP) derived from Cariolous versicolor in a herpes viru s Type 2-transformed murine tumor (H238) model and to determine possib le mechanisms of action. BALB/c mice were inoculated subcutaneously (s .c.) with H238 tumor cells and randomized into groups. a) no tumor and no treatment control, b) tumor and Mo treatment control, c) tumor + I L-2 at 0 to 4 days, d) tumor + PSP at 0 to 10 days, e) tumor + IL-2 at 0 to 4 days + PSP at 0 to 10 days, and f) tumor + IL-2 at 15 to 19 da ys + PSP at 15 to 25 days. The IL-2 was administered s.c. at 2 x 10(4) i.u./mouse/injection; PSP was given s.c. at 2 mg/mouse/injection. No obvious toxicity was noted during the treatments. IL-2 and to a lesser extent, PSP significantly slowed (p<0.05) tumor progression when give n alone immediately after tumor cell injection. The combination of the two modalities did not significantly enhance the antitumor effect of lL-2 alone. However, mice receiving both agents had IL-2 in the plasma , their tumors expressed low levels of transforming growth factor-beta , and their splenocyte response to mitogenic stimulation was significa ntly higher than in untreated controls. Changes in blood leukocyte pop ulations and splenic oxidative burst capacity were associated with tum or presence, but not with the type of treatment. In vitro assays showe d that both IL-2 and PSP can suppress the uptake of H-3-thymidine by t umor cells and that the effect is move pronounced whent the agents are used in combination. These results indicate that IL-2 and PSP can slo w progression of H238 tumors and that the mechanisms of action may be related to their direct cytotoxic effects, as well to their immunomodu latory properties.