Interferons and Interleukin-2: Molecular Basis of Activity and Therapeutic Results

Metastatic renal cell carcinoma (RCC) is a tumor refractory to standard cytotoxic chemotherapy regimens. The rationale for the use of cytokines in this cancer is based upon compelling evidence that RCC is sensitive to immunological manipulation. Cytokine-based therapy with either interleukin-2 (IL-2) or interferon-α (IFN-α) can result in objective tumor responses in up to 15% of patients, and in selected patients, these responses may be durable. Subsequently these cytokines have impacted positively on both quality and quantity of life for thousands of RCC patients – and it seems probable that their full clinical potential has yet to be reached. The development of “targeted” therapies for clear cell RCC with the potential for greater antitumor activity and less toxicity has brought into question the role of cytokines in this patient population. However, no noncytokine therapy to date has proven curative in patients with metastatic RCC. A series of recently completed and ongoing clinical trials will partially define the future role of IFNs and IL-2 in sequence and in combination with newer “targeted” agents. As the knowledge of the role that IFN and IL-2 contribute to both innate and acquired immunity continues to expand, it seems probable that the structure and/or application of these cytokines will be further modulated for therapeutic advantage in RCC.