Ligand-Induced Degradation of a CAR Permits Reversible Remote Control of CAR T Cell Activity In Vitro and In Vivo

The authors created a chimeric antigen-receptor (CAR) that was capable of on-demand downregulation by fusing the CAR to a previously developed ligand-induced degradation domain. Addition of a small molecule ligand triggered exposure of a cryptic degron within the ligand-induced degradation domain (LID), resulting in proteasomal degradation of the CAR-LID fusion protein and loss of CAR on the surface of T cells.