Su Jingchao, Zeng Yifei, Song Zhuojin, Liu Yinglu, Ou Kaixin, Wu Yuhan, Huang Minhong, Li Yuhua, Tu Sanfang
Department of Hematology, Zhujiang Hospital, Southern Medical University, Guangzhou, 510280, Guangdong, China.
Guangdong Engineering Research Center of Precision Immune Cell Therapy Technology, Guangzhou, 510280, Guangdong, China.
J Hematol Oncol. 2025 Oct 24;18(1):90. doi: 10.1186/s13045-025-01745-8.
Chimeric Antigen Receptor T (CAR-T) cell therapy has revolutionized cancer immunotherapy, particularly in hematological malignancies. However, the clinical application of autologous CAR-T cells faces significant high cost and manufacturing challenges. Universal allogeneic CAR-T cells, derived from healthy donors, represent a promising solution to these obstacles. These "off-the-shelf" therapies aim to reduce the complexity and cost of CAR-T production. Despite exciting advancements in genome-editing technologies and promising clinical trial data, significant challenges remain, including graft-versus-host disease (GVHD), Host-versus-graft reaction (HVGR), off-target effects, genotoxicity, and manufacturing scalability. To address these concerns, genome-editing technologies such as ZFNs, TALENs, Meganucleases, CRISPR systems, base editing, and prime editing are being employed. This review summarizes the progress of universal allogeneic CAR-T cell therapies, addresses the critical challenges, and discusses the future directions for their clinical implementation.
嵌合抗原受体T（CAR-T）细胞疗法彻底改变了癌症免疫疗法，尤其是在血液系统恶性肿瘤方面。然而，自体CAR-T细胞的临床应用面临着成本高昂和制造方面的重大挑战。源自健康供体的通用型同种异体CAR-T细胞是解决这些障碍的一个有前景的方案。这些“现货供应”疗法旨在降低CAR-T生产的复杂性和成本。尽管基因组编辑技术取得了令人兴奋的进展，临床试验数据也很有前景，但仍存在重大挑战，包括移植物抗宿主病（GVHD）、宿主抗移植物反应（HVGR）、脱靶效应、基因毒性和制造可扩展性。为了解决这些问题，人们正在采用锌指核酸酶（ZFNs）、转录激活因子样效应物核酸酶（TALENs）、巨核酸酶、CRISPR系统、碱基编辑和引导编辑等基因组编辑技术。本综述总结了通用型同种异体CAR-T细胞疗法的进展，阐述了关键挑战，并讨论了其临床应用的未来方向。
