Figure 2. CAR-T construct designs.

(A) First-generation CARs contained an scFv and an additional signaling domain CD3ζ.

(B) The second generation included a secondary costimulator, CD28, or tumor necrosis factor ligand superfamily member 9 (4-1BB).

(C) Third-generation CARs were composed of two secondary costimulatory domains.

(D) Fourth-generation TRUCKs were modeled after second-generation CARs and contained gene expression cassette-inducing cytokines.

(E) The fifth generation of CARs consisted of an IL-2 receptor β-chain domain and a binding location for Janus kinase-signal transducer and activator of transcription pathway (JAK-STAT3/5) [16].

CAR-T, chimeric antigen receptor T; scFv, single-chain variable fragment; CD3ζ, cluster of differentiation 3ζ; CD28, cluster of differentiation 28; TRUCK, T cells redirected for universal cytokine-mediated killing; IL, interleukin