Modular structure of prototypical CAR. CAR shown dimerized on the cell surface demonstrating the key extracellular (A-B) and intracellular (C-E) domains. CARs may express 1, 2, or 3 signaling motifs within an endodomain to achieve a CAR-dependent fully-competent T-cell activation signal. The modular structure of the CAR's domains, for example, the scFv (V_L linked to V_H) region (A) and the flexible hinge and spacer, for example, from IgG4 hinge, C_H2, and C_H3 regions (B), allow investigators to change specificity through swapping of exodomains and achieve altered function by varying transmembrane and intracellular signaling moieties (C-E).