Combination Treatment with Irritant and Recombinant Interleukin 2 in the Peritoneal Cavity for Evoking Effective Anti‐tumor Activity: Generation of Lymphokine‐activated Killer Cells and Tumor‐specific Killer Cells

Meth A sarcoma, growing in the subcutaneous tissue of syngeneic BALB/c mice, regressed completely after an intraperitoneal (ip) injection of protease peptone (PP) (on day 6) followed by 2 ip administrations (on days 7 and 8) of human recombinant interleukin‐2 (IL‐2, 25 μg/day), whereas one such treatment alone had little effect on the tumor growth. While this combination treatment was effective in anti‐asialo GM1 antibody‐treated mice, no such effect was noted in T cell‐depleted ATXFL (thymectomized, irradiated and fetal liver cell‐reconstituted) mice. These results show that T cells are mainly responsible for this antitumor effect. Treatment with a combination of PP and IL‐2, but not with either PP or IL‐2 alone, resulted in a marked increase in the T cell population in the peritoneal cavity after the treatment. At an early stage after the combination treatment, both peritoneal exudate cells (PEC) and spleen cells exhibited killing activity with a promiscuous specificity. However, at a later stage, 7 days after the treatment, Meth A‐specific killer activity was observed in both PEC and the spleen. Meth A rechallenge was rejected by the mice in which the tumor had regressed, but the antigenically different Meth 1 was accepted by them. A similar result was obtained in Winn's neutralization test. These results suggest that this combination treatment, which is effective in the generation of lymphokine‐activated killer cells in the peritoneal cavity, finally resulted in the induction of tumor‐specific killer cells in the periphery. These results clearly show the anti‐tumor efficacy of combination treatment with PP and rIL‐2.