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. 2021 Oct 28;13(21):5418. doi: 10.3390/cancers13215418

Figure 3.

Figure 3

Potential design of CAR generation according to NK cell intracellular motifs and functions. From left to right: First generation CARs (1G) have an intracellular tyrosine-based activation motif, such as a CD3 ζ chain, DAP10 or DAP12. Second generation CARs (2G) include a co-stimulatory domain (CD28, 4-1BB or 2B4) in tandem with CD3ζ or DAP10 or DAP12. Third generation CARs (3G) contain two co-stimulatory elements (CD28, 4-1BB or 2B4) in tandem with CD3ζ or DAP10 or DAP12. Fourth generation CARs (4G or TRUCKs) are additionally modified with an inducible or constitutive expression cassette for a transgenic protein. NKG2D ectodomain with DAP10 and CD3ζ cytoplasmic signalling endodomain.