Progress in research of switchable chimeric antigen receptor T cells / 药学学报

ABSTRACT

In recent years, chimeric antigen receptor T cells (CAR-T) have been viewed as a target for successful treatment of hematologic malignancies. However, targeting conventional CAR-T cell has a series of side effects, such as cytokine storm, on-target off-tumor effect and neurotoxicity during treatment, and these side effects threatened patients' life. The extracellular domain of conventional CAR-T is a fixed single-chain variable fragment (scFv) that only targets one specific antigen, and once the tumor antigen is mutated or disappears, the CAR-T cell will fail. In recent years, a number of different switchable CAR-T cells have emerged. The design of switchable CAR-T cells is divided into two aspects CAR-T cell and molecular switch respectively, and the activation of CAR-T is completely dependent on the switch. It is not only universal, but also decreases the side effect of conventional CAR-T through controlling the molecular switch. We summarized the existing sCAR-T to provide an idea for CAR-T design and optimization, and lay a foundation for entering sCAR-T into clinical practice.