School of Life Sciences, Jiangsu University, 301 Xuefu Road, Zhenjiang, 212013, Jiangsu, China.
Department of Gastroenterology, The Affiliated Suqian First People's Hospital of Nanjing Medical University, Suqian, Jiangsu, China.
Hum Cell. 2022 Mar;35(2):441-447. doi: 10.1007/s13577-022-00670-z. Epub 2022 Jan 15.
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.
表达嵌合抗原受体 (CAR) 的工程化 T 细胞对血液系统恶性肿瘤具有显著的治疗效果。然而，CAR-T 细胞在实体瘤上的效果较差，主要是由于 CAR-T 细胞的持久性较弱，这可能是由 T 细胞死亡引起的。CAR-T 细胞的显著激活诱导的细胞死亡 (AICD) 是由反复的抗原刺激引发的。T 细胞的 AICD 的特征是死亡受体的上调和 T 细胞的低持久性。了解 AICD 的机制对于提高 CAR-T 细胞对实体瘤的抗肿瘤作用至关重要。许多方法已应用于 CAR-T 细胞修饰，以增强其抗凋亡能力。在这篇综述中，我们总结了 CAR-T 细胞中 AICD 的分子机制以及在 CAR-T 细胞治疗中抗 AICD 的进展。
