fig4

Figure 4. The structural evolution across the five generations of chimeric antigen receptors (CARs) is defined by progressive enhancements to the intracellular signaling domain, which transitions from a solitary CD3ζ chain in the first generation to incorporate one or more costimulatory domains and finally to the fifth generation CAR, which contains the cytokine receptor signaling motifs, as detailed in the section “Structure and design of CAR-NK cell. Created in BioRender. Tong, C. (2025) https://BioRender.com/oem97rz. CD: Cluster of differentiation; CAR-NK: chimeric antigen receptor-natural killer; IL: interleukin; JAK: Janus kinase; STAT: signal transducer and activator of transcription.