Zha Chenyu, Song Jialu, Wan Ming, Lin Xiao, He Xiaolin, Wu Ming, Huang Rui
The Second School of Clinical Medicine, Southern Medical University, Guangzhou, Guangdong, China.
Department of Hematology, Zhujiang Hospital of Southern Medical University, Guangzhou, Guangdong, China.
Ther Adv Hematol. 2024 Jul 23;15:20406207241263489. doi: 10.1177/20406207241263489. eCollection 2024.
Chimeric antigen receptor T-cell (CAR-T) therapy, which has demonstrated notable efficacy against B-cell malignancies and is approved by the US Food and Drug Administration for clinical use in this context, represents a significant milestone in cancer immunotherapy. However, the efficacy of CAR-T therapy for the treatment of acute myeloid leukemia (AML) is poor. The challenges associated with the application of CAR-T therapy for the clinical treatment of AML include, but are not limited to, nonspecific distribution of AML therapeutic targets, difficulties in the production of CAR-T cells, AML blast cell heterogeneity, the immunosuppressive microenvironment in AML, and treatment-related adverse events. In this review, we summarize the recent findings regarding various therapeutic targets for AML (CD33, CD123, CLL1, CD7, etc.) and the results of the latest clinical studies on these targets. Thereafter, we also discuss the challenges related to CAR-T therapy for AML and some promising strategies for overcoming these challenges, including novel approaches such as gene editing and advances in CAR design.
嵌合抗原受体T细胞（CAR-T）疗法在治疗B细胞恶性肿瘤方面已显示出显著疗效，并已获得美国食品药品监督管理局批准在此背景下用于临床，这代表了癌症免疫治疗的一个重要里程碑。然而，CAR-T疗法治疗急性髓系白血病（AML）的疗效不佳。将CAR-T疗法应用于AML临床治疗所面临的挑战包括但不限于AML治疗靶点的非特异性分布、CAR-T细胞生产困难、AML原始细胞异质性、AML中的免疫抑制微环境以及与治疗相关的不良事件。在本综述中，我们总结了关于AML各种治疗靶点（CD33、CD123、CLL1、CD7等）的最新研究结果以及针对这些靶点的最新临床研究结果。此后，我们还讨论了AML的CAR-T疗法相关挑战以及克服这些挑战的一些有前景的策略，包括基因编辑等新方法以及CAR设计方面的进展。
