Department of Bio-Therapeutics, The First Medical Centre, The General Hospital of Chinese People's Liberation Army, Beijing 100853, China.
Department of Hematology, The Second Affiliated Hospital, College of Medicine, Zhejiang University, Hangzhou, Zhejiang 310009, China.
Chin Med J (Engl). 2023 Feb 5;136(3):269-279. doi: 10.1097/CM9.0000000000002476.
Remarkable improvement relative to traditional approaches in the treatment of hematological malignancies by chimeric antigen receptor (CAR) T-cell therapy has promoted sequential approvals of eight commercial CAR T products within last 5 years. Although CAR T cells' productization is now rapidly boosting their extensive clinical application in real-world patients, the limitation of their clinical efficacy and related toxicities inspire further optimization of CAR structure and substantial development of innovative trials in various scenarios. Herein, we first summarized the current status and major progress in CAR T therapy for hematological malignancies, then described crucial factors which possibly compromise the clinical efficacies of CAR T cells, such as CAR T cell exhaustion and loss of antigen, and finally, we discussed the potential optimization strategies to tackle the challenges in the field of CAR T therapy.
嵌合抗原受体(CAR)T 细胞疗法在血液系统恶性肿瘤治疗方面取得了显著优于传统方法的效果,这推动了在过去 5 年内先后批准了 8 种商业化的 CAR T 产品。虽然 CAR T 细胞的产品化正在迅速推动其在真实世界患者中的广泛临床应用,但它们的临床疗效的局限性及其相关毒性激发了对 CAR 结构的进一步优化和在各种情况下开展创新试验的大量研究。在此,我们首先总结了 CAR T 治疗血液系统恶性肿瘤的现状和主要进展,然后描述了可能影响 CAR T 细胞临床疗效的关键因素,如 CAR T 细胞耗竭和抗原丢失,最后,我们讨论了潜在的优化策略以应对 CAR T 治疗领域的挑战。