Cancer immunotherapy using local interleukin 2 administration

Peri-tumoural administration of human recombinant interleukin-2 (RIL-2) into C57BL/10ScSnPh (B10) mice carrying subcutaneous transplants of syngeneic methylcholanthrene (MC)-induced sarcomas substantially inhibited tumour growth. Experiments were designed to compare the tumour-inhibitory effect of highly purified RIL-2 with that of unpurified human and rat lymphoid interleukin-2 (IL-2) preparations. It was found that the effect of RIL-2 was significantly lower than that of the lymphoid IL-2 preparations. These findings indicate that other lymphokines may participate in the positive results of local IL-2 immunotherapy using unpurified lymphoid IL-2 preparations. However, the admixture of human recombinant interleukin-1 (RIL-1) did not potentiate the immunotherapeutic effects of RIL-2. Sensitivity of MC-induced sarcomas to local RIL-2 immunotherapy was a general phenomenon. The growth of approximately eighty percent (5/6) of the MC-induced sarcomas could be inhibited with local RIL-2 administration. Moreover, direct correlation between the sensitivity of tumours to the tumour-inhibitory effect of RIL-2 in vivo and their susceptibility to the cytolytic effect of RIL-2-activated syngeneic killer spleen (LAK) cells in vitro was observed. This correlation indicates that LAK cells represent the effector cell mechanism responsible for the anti-tumour efficacy of local RIL-2 immunotherapy and that in vitro testing of sensitivity to the LAK cell-mediated cytolysis may be used to detect tumours responding to the local RIL-2 immunotherapy in vivo.