Fig. 4
From: A review on the advances and challenges of immunotherapy for head and neck cancer
Five generations of CAR-T cells. First-generation CAR-T cells include the CD3ζ alone as the intracellular domain, whereas the second-generation CARs consist of additional costimulatory intracellular domains, such as CD28 or 4-1BB (CD137). Third-generation CARs consist of two costimulatory intracellular domains, such as CD28 and 4-1BB. The fourth- and fifth-generation CAR-T cells are based on the second-generation ones. The fourth-generation CARs can induce the expression of cytokines, such as IL-12, whereas the fifth-generation CAR-T cells include an intracellular domain of cytokine receptors, such as IL-2Rβ