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. 2022 Aug 25;24(4):358. doi: 10.3892/ol.2022.13478

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Copyright: © Chen et al.

This is an open access article distributed under the terms of the Creative Commons Attribution-NonCommercial-NoDerivs License, which permits use and distribution in any medium, provided the original work is properly cited, the use is non-commercial and no modifications or adaptations are made.

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Figure 3. — Evolution of the development of CAR-T cell products: First-generation CAR-T cells only contain CD3ζ-derived signaling modules. Second-generation CAR-T cells contain a CD3ζ-derived signaling module and a co-stimulatory domain. Third-generation CAR-T cells contain a CD3ζ-derived signaling module and two co-stimulatory domains, including 4-1BB, CD28, OX40 or ICOS. Fourth-generation CAR-T cells contain a CD3ζ-derived signaling module, co-stimulatory domain and a cytokine (such as IL-12) producing module. Fifth-generation CAR-T cells consist of Zip CAR and zip FV with leucine adapters. The horizontal membrane in the middle is the cell membrane, which is a lipid bilayer. CAR-T, chimeric antigen receptor T-cell; VL, variable region of light chain; VH, variable region of heavy chain; FV, fragment variable; OX40, tumor necrosis factor receptor superfamily member 4; ICOS, inducible costimulatory molecule.