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CRISPR 基因组编辑与白血病免疫治疗的未来

英文原题:CRISPR Genome Editing and the Future of Leukaemia Immunotherapy.

PubMed 2026/05/06(内容时间) Health Sci Rep Q1 · IF 2.9(JCR 2025)

研究概要

虽然碱基编辑在精确性和功能保留方面表现优异,但当需要完全基因敲除时,CRISPR-Cas9 仍是首选。

中文摘要

背景与目的:白血病仍面临持续的治疗挑战,包括疾病复发以及标准治疗相关毒性。CRISPR 基因组编辑能够支持更具靶向性和安全性的疗法,正成为应对这些问题的有力工具。 方法:本文回顾 CRISPR 技术在白血病免疫治疗中的现有研究,重点关注四种常见白血病靶抗原:CD33、CD7、CD45 和 CD19。 结果:文章追溯 CRISPR 技术从传统 CRISPR-Cas9 到碱基编辑的发展,说明 CRISPR 平台如何被重新用于提高疗效和临床安全性。CD33 靶向研究显示,编辑策略可通过减少肿瘤外毒性使 AML 治疗更安全;CD7 研究显示,碱基编辑可在 T-ALL 免疫治疗中防止 T 细胞相互杀伤;CD45 研究表明靶向编辑有助于实现通用 CAR-T 细胞治疗;CD19 临床试验则支持针对儿童 B 急性淋巴细胞白血病(B-ALL)开发“现货型”疗法的可行性。 结论:碱基编辑在精准性和功能保留方面具有优势;若治疗目标是完全敲除基因,CRISPR-Cas9 仍是优选。随着肿瘤外毒性和相互杀伤问题得到解决,这些技术未来的临床影响有望扩大。

展开英文摘要原文

BACKGROUND AND AIMS: Leukaemia presents ongoing therapeutic challenges due to relapse and toxicity associated with standard treatments. By enabling more targeted and safer therapies, CRISPR genome editing is emerging as a powerful tool to address these issues. METHODS: We review current literature on CRISPR technologies in leukaemia immunotherapy, focussing on studies involving four key antigens commonly targeted in leukaemia: CD33, CD7, CD45 and CD19. RESULTS: We trace the evolution of CRISPR technologies from conventional CRISPR-Cas9 to base editing, highlighting how CRISPR platforms are being repurposed to enhance efficacy and clinical safety. Key studies targeting CD33 demonstrate how editing strategies can enable safer acute myeloid leukaemia (AML) therapies by reducing off-tumour toxicity; those addressing CD7 show how base editing prevents T-cell fratricide in T-cell acute lymphoblastic leukaemia (T-ALL) immunotherapy; studies focusing on CD45 illustrate how targeted editing facilitates universal CAR T-cell therapy; and clinical trials on CD19 support the feasibility of "off-the-shelf" treatments against paediatric B-cell acute lymphoblastic leukaemia (B-ALL). CONCLUSION: While base editing excels in precision and functional preservation, CRISPR-Cas9 remains preferred when complete gene knockout is desired. As off-tumour toxicity and fratricide are addressed, the future clinical impact of these technologies is poised to expand.

论文信息

作者
Rai D、Terranova U
单位
Faculty of Medicine and Health Science University of Buckingham Buckingham UK.United Kingdom
期刊
Health science reports2026 May
原文标识
PubMed 42110387 · DOI 10.1002/hsr2.72497