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Cytokines have a remarkable ability to potently activate immune cells, making them attractive for cancer immunotherapy. But their lack of specificity has defeated most efforts to make them into drugs. That’s because cytokine receptors are widely distributed across many cell types, leading to side effects, often severe. Interleukin (IL)-2, for example, is a powerful survival and expansion factor for effector T cells, but it also binds to receptors on natural killer (NK) cells, regulatory T cells and vascular endothelial cells. Side effects of recombinant IL-2 (Proleukin (aldesleukin), first approved in 1992) can include massive inflammation and fatal vascular leak syndrome.