Centre Léon Bérard and Centre de Recherche en Cancérologie de Lyon, Lyon, France.
Cellectis, Paris, France.
Nat Rev Drug Discov. 2020 Mar;19(3):185-199. doi: 10.1038/s41573-019-0051-2. Epub 2020 Jan 3.
Autologous chimeric antigen receptor (CAR) T cells have changed the therapeutic landscape in haematological malignancies. Nevertheless, the use of allogeneic CAR T cells from donors has many potential advantages over autologous approaches, such as the immediate availability of cryopreserved batches for patient treatment, possible standardization of the CAR-T cell product, time for multiple cell modifications, redosing or combination of CAR T cells directed against different targets, and decreased cost using an industrialized process. However, allogeneic CAR T cells may cause life-threatening graft-versus-host disease and may be rapidly eliminated by the host immune system. The development of next-generation allogeneic CAR T cells to address these issues is an active area of research. In this Review, we analyse the different sources of T cells for optimal allogeneic CAR-T cell therapy and describe the different technological approaches, mainly based on gene editing, to produce allogeneic CAR T cells with limited potential for graft-versus-host disease. These improved allogeneic CAR-T cell products will pave the way for further breakthroughs in the treatment of cancer.
自体嵌合抗原受体 (CAR) T 细胞改变了血液系统恶性肿瘤的治疗格局。然而,与自体方法相比,同种异体 CAR T 细胞来自供体具有许多潜在优势,例如可立即获得用于患者治疗的冷冻保存批次,CAR-T 细胞产品可能标准化,有时间进行多次细胞修饰、再给药或针对不同靶点的 CAR T 细胞联合治疗,并且采用工业化流程可降低成本。然而,同种异体 CAR T 细胞可能会导致危及生命的移植物抗宿主病,并且可能会被宿主免疫系统迅速清除。开发解决这些问题的下一代同种异体 CAR T 细胞是一个活跃的研究领域。在这篇综述中,我们分析了用于优化同种异体 CAR-T 细胞治疗的不同 T 细胞来源,并描述了不同的技术方法,主要基于基因编辑,以产生具有有限移植物抗宿主病潜力的同种异体 CAR T 细胞。这些改进的同种异体 CAR-T 细胞产品将为癌症治疗的进一步突破铺平道路。
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