Sophisticated bioengineering approaches are under development to enhance the potency, specificity, and safety of T cell therapies. Suicide switches, AND gating, and adaptor CAR platforms are being developed to mitigate CAR-mediated toxicity. Ectopic expression of c-Jun or genetic deletion of NR4a factors endows CAR T cells with exhaustion resistance, potentially improving efficacy in solid tumors and enhancing persistence. CAR T cells can also be engineered to secrete specific factors to augment expansion or persistence (e.g., IL-7, IL-12, IL-15, or IL-21), diminish the need for a lymphodepleting regimen, resist the suppressive tumor microenvironment (e.g., secretion of IL-18, expression of a truncated transforming growth factor β [TGF-β] receptor), or act as tumor-specific drug delivery vehicles (e.g., local secretion of anti-PD-1).