Application and progress of CAR therapy on malignances: from CAR-T to CAR-NK
DOI:
https://doi.org/10.61173/ve5wzw54Keywords:
CAR-T, CAR-NK, therapy, malignancesAbstract
For some malignances that are highly aggressive and metastatic are usually considered incurable. However, with the advent of immunotherapy, this therapy could be possibly effective after other three major therapies: surgery, radiation, chemotherapy. As an emerging immunotherapy, chimeric antigen receptor (CAR) T cells have been applied to treat hematologic malignances and some patients achieved long-term remission and temporary cure. However, CAR-T cells also bring side effects such as cytokine release syndrome (CRS), neurotoxicity, etc. Moreover, CAR-T cells did not perform well in solid tumors, for the reason that CAR-T cells are difficult to break through external barrier of solid tumors, at the same time maintain cytotoxicity and persistence inside. Therefore, we introduce CAR-NK cells therapy on the basis of CAR-T cells. At present all CAR-NK cell therapies are in clinical trials, its effectiveness has been initially observed. Compared with CAR-T cells, patients with hematologic malignances received CAR-NK cell therapies showed few side effects such as CRS and neurotoxicity.
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[131] Niu Z, Chen G, Chang W, Sun P, Luo Z, Zhang H, et al. Chimeric antigen receptor-modified macrophages trigger systemic anti-tumour immunity. J Pathol. 2021;253(3):247–257. Figure 1: Basic structure of CAR-T. The basic structure of CAR-T consists of four parts, extracellular antigen binding domain, hinge region, transmembrane domain, and intracellular signaling domain. The function of the extracellular antigen-binding domain is to recognize and bind specific antigens, the function of the hinge region is to expose the antigen-binding domain to the cell surface, the function of the transmembrane region is to dock the CAR to the immune cells, and the intracellular signaling domain is mainly responsible for transducing signals to activate the immune cells to attack the target cells. Four generations of CAR-T cells have been developed, and each generation of CAR-T cells differs in the structure of the intracellular signaling domain. The first generation CAR-T cell intracellular signaling domain includes a CD3ζ, the second generation CAR-T cell includes a CD3ζ and a co-stimulatory domain, the third generation CAR-T cell includes a CD3ζ and multiple co-stimulatory domains, and the fourth generation CAR-T cell adds other structures on top of this that can assist the CAR-T cell in releasing cytokines to fight against TME, etc. CAR-T. CAR-NK, CAR-Macrophage have similar structures. Dean&Francis
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