Fig. 1

Schematic representation of a chimeric antigen receptor (CAR) T-cell. CAR T-cells are typically produced by transducing T-lymphocytes with a transgene encoding a synthetic antigen receptor. This transgene is integrated into the T-cell genome, transcribed and translated into a CAR protein. The core functional components of a CAR are binding and signaling domains separated into extracellular and intracellular compartments, respectively. The extracellular binding portion of the receptor is typically comprised of a single-chain variable fragment derived from the variable regions of an antibody that recognizes specific tumor antigens, together with a spacer that provides flexibility to the binding domain. The transmembrane domain connects the binding domain with intracellular signaling moieties. The TCR-derived CD3ζ chain drives T-cell activation and is fused in tandem with co-stimulatory endodomains that allow for robust and sustained function