Immunotherapy of metastatic renal cell carcinoma

Abstract

Renal cell carcinoma (RCC) evokes an immune response, which occasionally has resulted in spontaneous and dramatic remissions. In an attempt to reproduce or accentuate this response, various immunotherapeutic strategies have been studied. The most consistent antitumor activity has been reported with interferon-alpha (IFN-alpha) and interleukin-2 (IL-2). In recent years, randomized trials have suggested that high-dose, intravenous bolus IL-2 is superior in terms of response rate and possibly in terms of response quality to regimens that involve either low-dose IL-2 and IFN-alpha, intermediate- or low-dose IL-2 alone, or low-dose IFN-alpha alone. More significantly, investigations associated with those trials suggested that the potential exists for identifying predictors of response (or resistance) and limiting IL-2 therapy to those patients who hare most likely to benefit. Although the role of low-dose, single-agent cytokines is limited, combinations of cytokines with targeted therapy may have merit. Several studies, including 2 completed, large, phase 3 trials of interferon plus bevacizumab versus interferon alone, have demonstrated superior efficacy with the combination regimen compared with cytokine monotherapy and suggested the potential of an additive effect that requires further exploration. For patients who are unlikely to benefit from IL-2 or who are unable to receive it, the emergence "targeted immunotherapy" offers hope for improved clinical outcome. Improvements in patient selection, novel agents, and combination therapy will be required to optimize the benefits of immunotherapy in metastatic RCC as the list of effective therapies grows.