Recombinant interleukin 2 (IL-2) is effective in treating advanced-stage metastatic cancer; however, for many patients its use is limited by severe systemic toxicity. In this issue, Shanafelt and colleagues have developed an IL-2 variant, called BAY50-479, that has significantly reduced toxicity while retaining potent therapeutic effects. Some evidence has suggested that IL-2's therapeutic effects are mediated by T-cell activation and its toxic effects by natural killer (NK) cell activation, by IL-2 binding to different forms of the IL-2 receptors residing on their surface. These findings have prompted the researchers to eliminate IL-2 residues that interact with the NK-cell receptor in order to reduce IL-2's toxic effects. The BAY50-479 variant that they produced exhibited a ∼3,000 fold selectivity for T cells over NK cells in vitro. They went on to test its in vivo effects and found that its ability to inhibit tumor metastasis in a mouse model was comparable to that of IL-2; however its toxicity in chimpanzees was greatly reduced (see p. 1197).