Figure 3.

Generations of chimeric antigen receptor T-cell (CAR-T cell) construct designs. (A) First-generation chimeric antigen receptors (CARs) were composed of a single-chain variable fragment (scFv) specific for a cancer marker, hinge and transmembrane domains, and the cytoplasmic CD3ζ signaling domain. (B) Second-generation CARs included the coupling of a co-stimulatory signaling domain. (C) Third-generation CARs incorporated a second co-stimulatory signaling domain. (D) Fourth-generation CARs were based on the structure of the second-generation CARs, plus an inducible gene expression cassette encoding a transgenic cytokine. (E) Fifth-generation CARs contain an IL-2 receptor β-chain domain and a binding site for STAT3.