Cytokine-Based Combined Modality Approaches to the Treatment of Murine Renal Cancer

Abstract

Biological response modifiers (BRM) are being developed as a potential fourth modality for cancer treatment to supplement the three currently accepted modalities, chemotherapy, radiotherapy, and surgery (1). There are several possible approaches to the use of immunoactive cytokines as part of combined modalities for cancer treatment. First, cytokines can be used in combination with one or more of the traditional modalities for cancer treatment. The rationale for such an approach is that either the mechanisms for the antitumor effects of the cytokines versus those of the other modality will differ leading to enhanced antitumor effects, or that the effects of one will enhance the activity of the other. In either case the efficacy of the combination should be greater than either modality alone. Second, different combinations of cytokines should be complementary based on their interaction as part of the cytokine cascade that regulates immune responses. We are studying different preclinical models that fall into both types of combined modality approaches. It has been reported that interleukin 1 (IL-1) can protect mice from the acute toxicity of some chemotherapeutic drugs (2–4) and that this ability to dose escalate chemotherapy translates into enhanced antitumor efficacy (4), although some late toxicity becomes evident (4). In addition, we are studying the hematoimmunological effects of various T cell-stimulating cytokines (5–7) under the hypothesis that the enhancement of the appropriate T cell functions will lead to increased antitumor efficacy.