TCR mimic CAR-T

Chimeric antigen receptors (CAR) that mimic T cell receptors (TCR) on eliciting peptide-major histocompatibility complex (pMHC) specific T cell responses hold great promise in the development of immunotherapies against solid tumors, infections, and autoimmune diseases. However, broad applications of TCR-mimic (TCRm) CARs are hindered to date largely due to lack of a facile approach for the effective isolation of TCRm CARs. We establish a highly efficient platform technology for de novo discovery of functional TCRm CARs from human naïve repertories with high potency, selectivity, sensitivity, and persistence. Beyond oncology and TCRm CAR, this development should have applications for the discovery of diverse immunotherapy modalities targeting MHC restricted antigen peptides for the treatment of infectious and autoimmune diseases.