Chimeric antigen receptor (car)-engineered t cells : structure, applications, challenges and strategies

specific type of immune therapy using chimeric antigen receptor (CAR )-engineered T cells has emerged as an exciting new approach for cancer immunotherapy and beyond. CARs consist of an antigen recognition domain, usually a single-chain variable fragment of an immunoglobulin, linked to T-cell activation (CD3ζ) and co-stimulation (commonly CD28 or 4-1BB) intracellular signaling domains. Upon antigen ligand interacting, CAR T cell becomes activated, proliferates, and eliminate target tumor cells expressing specific antigens. various tumor-associated antigens (TAAs) could act as target antigens for CAR-T cells. Despite tremendous successes to eliminate tumors shown in some clinical trials, However, CAR-T cell therapy involves Severe treatment-related toxicities including ; cytokine-release syndrome(CRS ) and Neurotoxicity , termed CAR-T-cell-related encephalopathy syndrome (CRES), and on-target, off-tumor toxicity, resulting from the recognition of normal cells by CAR-T cells which is related to poor control of the dose, location, and timing of T cell activity. Many strategies have been reported to improve the safety and efficacy of CAR modified-T cells, including ; suicide gene ( iCasp9 , HSV-TK ,Antibody-mediated depletion), inhibitory CAR, Synthetic Notch (synNotch) , Masked CAR, dual-antigen receptor, and the use of exogenous molecules as switches to control the CAR-T cell functions. In This review , we discusses the structure and evolution of CAR T cells, describe how antigenic targets are selected, the application of the CAR T cell therapy, its challenges, and recent potential strategies to enhance the safety of CAR modified T cells.

Keywords:

Gene and Cancer , Cell and Cancer , Cancer Genetics , Cancer Treatment and Management , Targeted Cancer Therapy