Synthetic receptors for logic gated T cell recognition and function

Adoptive cell therapy with T cells engineered with customized receptors that redirect antigen specificity to cancer cells has emerged as an effective therapeutic approach for many malignancies. Toxicity due to on target or off target effects, antigen heterogeneity on cancer cells, and acquired T cell dysfunction have been identified as barriers that can hinder successful therapy. This review will discuss recent advances in T cell engineering that have enabled the application of logic gates in T cells that can mimic the integration of natural signaling pathways and act in a cell intrinsic or extrinsic fashion to precisely target tumor cells and regulate effector functions, potentially overcoming these barriers to effective therapy.