[cv]

The cytokine interleukin-2 (IL-2) plays important roles in regulating the immune response, including, most notably, the stimulation of T-cell expansion after activation by antigen. Since T cells have the capacity to recognize and destroy tumor cells, IL-2 has shown efficacy as an agent for tumor immunotherapy. However, its use in cancer treatment has been limited by severe systemic toxicity, which results predominantly from the stimulation of natural killer (NK) cells. Since most NK cells express only the beta chain and the common gamma chain of the IL-2 receptor (IL-2Rb and gc, respectively), while activated T cells express these as well as the alpha chain (IL-2Ra or CD25), we are attempting to increase the specificity of IL-2 stimulation for T cells by engineering IL-2 for high-affinity binding to IL-2Ra. Such mutants would exert the effects of wild-type IL-2 at sub-toxic concentrations and may therefore serve as more effective agents for the immunotherapy of cancer.