Figure 3.

Generations of chimeric antigen receptors. The first-generation CARs have only one cytoplasmic signal transduction domain (e.g., CD3ζ). The second-generation CARs contain an intracellular co-stimulation domain (e.g., 4-1BB or CD28). The third-generation CARs have two co-stimulatory domains (e.g., CD28 and 4-1BB). The fourth-generation CARs additionally contain a NFAT-responsive expression element for an inducible transgenic product (e.g., an IL12-inducer element, leading to IL12 gene transcription). The fifth-generation CARs have an additional set of intracellular domains of cytokine receptors (e.g., IL2Rβ chain fragment, resulting in JAK/STAT activation). The figure was partly created by using www.biorender.com, accessed on 27 May 2023.