Effect of local tumor irradiation and interleukin-2 therapy in different murine tumors.

Abstract

The combined effect of local tumor irradiation and systemic immunotherapy was investigated in different murine tumors. Pulmonary metastases were induced in C57BL/6 mice by intravenous injection of MCA 205 sarcoma or B16 melanoma, and in BALB/c mice by injection of Renca renal adenocarcinoma. Local tumor irradiation was delivered to the left lung only at various doses of 300-800 cGy, followed by systemic administration of interleukin-2 (IL-2). All three tumor models responded to radiation in a dose-dependent fashion. MCA 205 and Renca tumor models were sensitive to IL-2, whereas the B16 tumor model responded poorly to IL-2 therapy. Local tumor irradiation enhanced the effects of immunotherapy in the two tumor models (MCA 205 and Renca) that responded to IL-2. These studies confirm that local tumor irradiation can greatly enhance the effectiveness of immunotherapy in a variety of tumor models, provided that the tumor is IL-2 responsive. There is further need to characterize the mechanism of the radiation-immunotherapy interaction and to initiate clinical trials to identify the variety of malignancies that may respond to this form of therapy.