Advances in CAR design.

Abstract Chimeric antigen receptor (CAR) T cells have revolutionized the management of B cell malignancies. These synthetic molecules are composed of peptide fragments from several distinct immune cell proteins and link highly-specific antigen recognition with potent T cell activation. Despite impressive results in many, less than half of patients treated will achieve durable remission after CAR therapy. Recent studies have identified the central role that each structural component of the CAR molecule plays in regulating T cell function. Significant effort has been dedicated to exploring strategies to improve the design of CARs themselves or integrate their activity with other regulatory circuits to enable more precise function. In this review, we will summarize recent pre-clinical and clinical studies that have evaluated novel CAR design formats.