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'Off-the-shelf' allogeneic CAR T cells: development and challenges.
Nature Reviews Drug Discovery ( IF 122.7 ) Pub Date : 2020-01-03 , DOI: 10.1038/s41573-019-0051-2
S Depil 1 , P Duchateau 2 , S A Grupp 3 , G Mufti 4 , L Poirot 2
Affiliation  

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.

中文翻译:

“现成的”同种异体CAR T细胞:发展和挑战。

自体嵌合抗原受体(CAR)T细胞已经改变了血液系统恶性肿瘤的治疗前景。然而,与自体方法相比,使用来自供体的同种异体CAR T细胞具有许多潜在的优势,例如可立即使用冷冻保存的批次进行患者治疗,CAR-T细胞产品的可能标准化,多次细胞修饰的时间,重做或组合靶向不同目标的CAR T细胞数量减少,并通过工业化流程降低了成本。但是,同种异体CAR T细胞可能会导致威胁生命的移植物抗宿主病,并可能被宿主免疫系统迅速消除。解决这些问题的下一代同种异体CAR T细胞的开发是一个活跃的研究领域。在这篇评论中,我们分析了不同的T细胞来源,以进行最佳的同种异体CAR-T细胞治疗,并描述了主要基于基因编辑的不同技术方法,以生产出同种异体CAR T细胞的潜在可能性有限。这些改良的同种异体CAR-T细胞产品将为癌症治疗的进一步突破铺平道路。
更新日期:2020-01-04
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