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. 2023 Jul 3;16:515–532. doi: 10.2147/OTT.S341179

Figure 1.

Figure 1

Generations of chimeric antigen receptors. Chimeric antigen receptors consist of a targeting moiety (most commonly an scFv as illustrated here), a spacer/hinge, transmembrane domain and a signaling endodomain. Antigen recognition is direct provided that a target cell (here designated as antigen-presenting cell) expresses the target antigen on the cell surface. In first generation (1G) CARs, the endodomain contains an ITAM (immunoreceptor tyrosine-based activation motif)-containing activating module. Most commonly CD3 zeta is used for this purpose since each monomer contains 3 ITAMs. Second generation (2G) CARs contain a co-stimulatory domain placed upstream of CD3 zeta and most commonly derived from CD28 or 4–1BB. Third generation (3G) CARs contain two complementary co-stimulatory units while armored CARs produce a cytokine such as IL-12 or IL-18.