We have studied the anti-
tumor effects of human recombinant
IL-2, alone or in association with LAK cells, in mice transplanted subcutaneously (s.c.) with the following syngeneic
tumors: highly metastatic Friend
leukemia cells (FLC), nonmetastatic FLC,
lymphoma RBL-5 cells and HeJ16
fibrosarcoma cells. In these
tumor models, peri-tumoral
injections of
IL-2 were more effective in inhibiting
tumor growth than a systemic treatment. Although s.c.
IL-2 treatment resulted in marked inhibition of
tumor growth in mice injected s.c. with highly metastatic FLC, it was not effective in inhibiting growth of FLC in the liver and spleen.
IL-2 therapy was more effective at increasing survival time in mice transplanted with non-metastatic FLC or with RBL-5 cells. In mice transplanted with HeJ16
fibrosarcomas, s.c.
IL-2 treatment resulted in highly significant anti-
tumor effect and survival of 70% of
tumor-injected mice. No general correlation was found between in vitro sensitivity or resistance to the cytolytic activity of LAK cells and the anti-
tumor effects observed in vivo.
Subcutaneous injection of
IL-1 beta in mice transplanted with highly metastatic FLC resulted in a marked increase in survival time and inhibition of metastatic
tumor growth in liver and spleen. Combined treatment of
IL-1 beta and
IL-2 produced a synergistic anti-
tumor effect: 60% of mice injected with highly metastatic FLC survived. Combined IL-1/IL-2 treatments exerted no anti-
tumor activity either in DBA/2 mice injected with antibody to
Thy 1.2 antigen or in nude mice, indicating that T cells play important roles during IL-1/IL-2
therapy. In vitro treatment of FLC with
IL-1 beta resulted in a slight inhibition of cell multiplication, whereas even high doses of
IL-2 did not affect FLC multiplication. Our results indicate that local combined treatments with
IL-1 and
IL-2 can induce potent, host-dependent (T cell-mediated) anti-
tumor effects against highly malignant
tumors.