Figure 1.

Structure–function of US Food and Drug Administration (FDA)-approved CD19 chimeric antigen receptors (CARs).

Second-generation CARs incorporate an extracellular antigen-binding moiety (scFv) linked to hinge (H) and transmembrane (TM) domains, a costimulatory and a T-cell-activating element. Each structural domain contributes to the overall CAR functionality. Current FDA-approved CAR T cells comprise an anti-CD19 single-chain variable fragment (scFv) fused to CD28 H/TM (blue), intracellular CD28 (blue) and CD3ζ signalling domains [‘1928ζ’ (axicabtagene ciloleucel, Yescarta)] or an anti-CD19 scFv linked to CD8 H/TM (magenta), 4-1BB costimulatory (turquoise) and CD3ζ domains [‘19BBζ’ CAR T cells (tisagenlecleucel, Kymriah)].