Figure 1.

Structure of chimeric antigen receptors. (A) structure of antibody indicating hinge and CH2/CH3 domains incorporated into chimeric antigen receptor (CAR) spacer, and variable light and heavy chains incorporated into ScFv component of CAR. (B) prototypic first to third generation CAR structures incorporating the CH2-CH3-hinge spacer. (C) Example CARs used in clinical studies: The 14G2A anti-GD2 first generation was an early clinical study in solid cancer [11], whereas KTE-C19 and CTL019 are FDA approved agents targeting CD19. Note the different transmembrane regions derived from adjacent co-stimulatory domains. (D) CARs are thought to be expressed at the cell surface as dimers linked by disulphides within the spacers. Each region of a CAR presents an opportunity for engineering strategies.