Chimeric antigen receptor T cell structure, its manufacturing, and related toxicities; A comprehensive review

Abstract

Cancer is the leading cause of death globally after cardiovascular diseases. Conventional therapeutic strategies have had minimal success rate. Recently, immunotherapy, particularly chimeric antigen receptor T cells (CAR T cells), has emerged as the most effective against cancer. A patient’s T lymphocytes have artificial chimeric antigen receptors genetically engineered on their surfaces to target specific antigens present on the surfaces of the cancer cell. A typical chimeric antigen receptor includes four domains, each of which serves a distinct purpose; the antigen recognition domain at the exterior of the cell is responsible for antigen recognition, the hinge region and transmembrane domain provides stability whereas, the intracellular domain in the endodomain of the receptor plays a crucial role in transmitting signals to activate the effector function of CAR T cells. Since CARs discovery, many properties have been added to CAR T cells to improve their effectiveness against the cancer. CAR T cell manufacturing processes involve; Isolation of lymphocytes, T cell selection and expansion, Gene transfer, formulation, quality assurance, and T cell infusion. Each of these CAR T cell engineering steps requires rigorous experimental processes done by a skillful team of researchers. A mistake during the manufacturing process may result in life-threatening consequences. Despite CAR T effectiveness, it imposes severe and unwanted side effect such as Cytokine Release Syndrome (CRS) and Immune effector Cell-Associated Neurotoxicity Syndrome (ICANS). As a result, CAR T-cell therapy must be accompanied by prompt treatment of the imminent side effects that may arise.

Keywords

• Chimeric antigen receptor
• CAR T-cell
• Cancer
• Cytokine release syndrome
• Lymphocytes
• and Immune effector cell-associated neurotoxicity syndrome