Figure 1.

(A) The basic structure of a CAR: extracellular domain, transmembrane domain, and intracellular domain. (B) The development of the five generations of CARs. The first generation only contained the CD3ζ chain functional energy domain9; the second generation contained CD3ζ+ a costimulatory molecular domain (CD28, 4-1BB, etc.); the third generation contained CD3ζ and two costimulatory molecular domains; the fourth generation included suicide gene editing, immune factor modification, and other integrated and refined regulatory tools; the fifth generation included simultaneous activation of TCR, costimulatory domain, and cytokine triple signaling.