Engineering human T cells with antigen receptors for immune regulation in autoimmune disease and transplantation

Engineered cell therapies have revolutionized the treatment of immune disorders; most notably, chimeric antigen receptors (CARs) have been used to generate antigen-specific T cells capable of targeting and eliminating tumors. Ongoing research extends similar principles to induce immune tolerance in autoimmune diseases and transplantation by leveraging the immunosuppressive properties of regulatory T cells (Tregs) and co-opting conventional T cells for tolerogenic applications. In this review, we highlight the diverse uses of engineered antigen receptors to generate human T cell-based therapies, spanning a variety of disease contexts and focusing primarily on CAR Tregs. We further summarize work that aims to improve therapeutic potency and safety, including approaches to enhance suppressive pathways and optimize antigen receptor design and regulation. Finally, as CAR Tregs and similar therapies move to the clinic, we discuss the practical implications of translation and methods that utilize off-the-shelf products and in vivo gene delivery.