Enhancing regulatory T cell function for adoptive CAR Treg therapy to treat autoimmune disease

Autoimmune diseases remain a major clinical challenge, with limited therapies that offer durable remission without broad immunosuppression. Chimeric antigen receptor (CAR) regulatory T cell (Treg) therapy offers a promising novel approach by redirecting the natural suppressive capacity of Tregs in an antigen-specific, controlled manner. However, the clinical translation of CAR Tregs is limited by challenges in maintaining regulatory T cell identity, function, and persistence over time. To address these limitations, we have engineered a panel of CAR constructs targeting myelin antigens, with the goal of developing a CNS-specific CAR Treg therapy for multiple sclerosis and related autoimmune diseases. Our objectives are to improve the efficacy, stability, and persistence of CAR Treg candidates in syngeneic mouse models of CNS autoimmunity by enhancing CAR Treg manufacturingand integrating Treg-associated signaling domains and regulatory proteins to reinforce their suppressive capacity and lineage stability. Our work will establish an innovative next-generation CAR Treg platform designed to achieve durable autoimmune suppression and enable translation to clinical applications