Fig. 3

The types of CAR T cell. CAR is a hybrid receptor for antigen that is part of the antibody and part of the TCR and has two domains: extracellular antigen binding portion and an intracellular signaling domain. The extracellular domain includes the single-chain variable fragment (scFv), hinge with transmembrane domain (TM), and intracellular T cell activation domain of CD3ζ included three immunoreceptor tyrosine-based activation motifs (ITAMs). In the first-generation CAR T cell, we see a single structure of CD3ζ that acts as a signal transmitter from the endogenous T cell receptor that does not have enough power to activate the T cell and kill the target cell. CARs without costimulatory have no special function, so in the second generation costimulatory such as CD28 or 4-1BB were added to the cytoplasmic domain. This improves the proliferation and response process and increases the life of the CART cells. In the third generation, use a large number of signaling domains to produce potent cytokines with greater lethality. They equipped the fourth generation with nuclear factor activated T(NFAT) cells that stimulate cytokines such as interleukin 12. The fifth generation CARS contains IL-2Rβ, which activates the Janus kinases (JAKs) and signal transducer and transcription activator (STAT) signaling pathways. Function of costimulatory: CD28-mediated co-stimulation is important for regulating lymphocyte proliferation and survival. OX40 stimulates the production of interleukin 2. 4-1BB (CD137) plays an important role in maintaining T cell response signals and plays a major role in T cell survival and memory of CD8 + T cells