Figure 1. Chimeric antigen receptor and T-cell receptor structure.

A chimeric antigen receptor (CAR; left) has an extracellular antigen-binding domain made of antibody variable fragments, fused via a linker to an intracellular domain composed of the CD3ζ signaling domain of the T cell receptor (TCR) and a co-stimulatory domain. Transgenic TCRs (middle) are similar to endogenous TCRs (right) but have engineered antigen-binding domains specific for a tumor-associated target. TCRs require co-stimulation from separate receptors for full T cell activation. CARs bind to cell surface antigen, whereas TCRs recognize intracellular antigens that are presented on human leukocyte antigen molecules (HLA). Adapted from Nat. Rev. Drug Discov. 16, 301–304 (2017).⁵