Immunotherapy of murine and human tumors in mice with lymphokines and interleukin-2-propagated lymphocytes

The therapeutic efficacy of crude interleukin-2 (IL-2) preparations and of IL-2-propagated lymphocytes (cultured T cells; CTC) was assessed, with and without chemotherapy, in conventional mice and in athymic nude mice implanted with murine or human neoplasms. Treatment of conventional mice implanted with lung and mammary carcinomas by repeated administration of lowdose cyclophosphamide (CY), IL-2, and tumor-sensitized CTC resulted in delayed tumor onset, retarded tumor growth rate, prolonged survival, and a higher cure rate as compared with mice receiving only CY. In some experiments, nonsensitized CTC (but not fresh lymphocytes) were therapeutically effective almost to the same extent as tumor-sensitized CTC. In most instances, the combination of chemo-therapy and IL-2 was significantly more curative than chemotherapy alone, and the addition of indomethacin improved the outcome of both chemotherapy and chemoimmunotherapy. Multiple administrations of IL-2 into athymic mice, before or after implantation of human tumors, delayed or completely inhibited tumor growth. IL-2 injections into normal, untreated, as well as X-irradiated or CY-treated mice, resulted in enhanced natural cytotoxicity and cytotoxic responsiveness in vitro to syngeneic tumors, greater proliferative response to phytohemagglutinin, and a tendency toward depressed proliferative responses to concanavalin A and to allogeneic leukocytes. It is concluded that the appropriate application of lymphokines and IL-2-propagated lymphocytes can be effective in the immunotherapy of experimental tumors and in immunorestoration of immunosuppressed mice. However, since crude lymphokine preparations have been employed in these studies, further analysis with purified lymphokines is required to confirm these observations.