Activation-induced cell death in CAR-T cell therapy

Engineered T cells expressing chimeric antigen receptors (CARs) with tumor specificity have shown remarkable therapeutic effects on hematologic malignancies. However, CAR-T cells are less effective on solid tumors mainly due to the weak persistence of CAR-T cells, which might be caused by T cell death. Significant activation-induced cell death (AICD) of CAR-T cells was triggered by repeated antigen stimulation. AICD of T cell is characterized by the upregulation of death receptors and low persistence of T cells. Understanding the mechanism of AICD is crucial to improve the anti-tumor effect of CAR-T cells against solid tumors. Many approaches have been applied in CAR-T cell modification to enhance their anti-apoptosis ability. In this review, we summarized the molecular mechanisms of AICD in CAR-T cells and the progresses of anti-AICD in CAR-T cells therapy.