Understanding of the human immune system has fueled development of numerous drugs, categorized as biologics, designed to mimic or inhibit natural immune responses. Recently, immunoengineering has emerged as a distinct discipline aimed at creating increasingly sophisticated therapeutics that can tailor immune responses for increased potency and/or diminished toxicity. On page 1037 of this issue, Sockolosky et al. (1) test the hypothesis that an engineered interleukin-2 (IL-2)–IL-2 receptor-β (IL-2Rβ) pair can expand effector T cells for cancer immunotherapy while avoiding the toxicities associated with administration of natural IL-2.