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应对肿瘤异体细胞免疫治疗中的移植物抗宿主病

英文原题:Addressing graft-versus-host disease in allogeneic cell-based immunotherapy for cancer.

查看英文原题

Addressing graft-versus-host disease in allogeneic cell-based immunotherapy for cancer.

PubMed 2025/05/02(内容时间) Exp Hematol Oncol Q1 · IF 17.5(JCR 2025)

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中文摘要

异基因细胞免疫疗法,特别是CAR-T 细胞疗法,是癌症治疗领域的重要进展,可提供可规模化且产品一致性较高的自体疗法替代方案。

然而,移植物抗宿主病(GvHD)风险限制了其广泛应用。本综述全面概述异基因细胞免疫疗法中的GvHD,并评价当前减轻其影响的策略。关键策略包括T细胞受体(TCR)敲除(KO)和T细胞受体α恒定区(TRAC)位点CAR敲入等基因工程方法。由于同种异体反应性较低,自然杀伤(NK)细胞和自然杀伤T(NKT)细胞等其他免疫细胞类型也可作为潜在解决方案。

此外,利用诱导多能干细胞(iPSC)的干细胞技术,可实现工程化CAR-T 细胞的标准化和规模化生产。评估这些策略的临床试验(如UCART19和CTX110)显示,在维持抗肿瘤疗效的同时预防GvHD具有良好前景。本综述还讨论了异基因细胞产品的生产考量,以及将临床前发现转化为临床成功所面临的挑战。随着这些问题逐步得到解决,异基因细胞免疫疗法持续发展,有望带来更易获得、可规模化且疗效更佳的癌症治疗。

展开英文摘要原文

Allogeneic cell-based immunotherapies, particularly CAR-T cell therapy, represent a significant advancement in cancer treatment, offering scalable and consistent alternatives to autologous therapies.

However, their widespread use is limited by the risk of graft-versus-host disease (GvHD). This review provides a comprehensive overview of GvHD in the context of allogeneic cell-based cancer immunotherapy and evaluates current strategies to mitigate its effects.

Key strategies include genetic engineering approaches such as T cell receptor (TCR) knockout (KO) and T cell receptor alpha constant (TRAC) CAR knock-in. Alternative immune cell types like natural killer (NK) cells and natural killer T (NKT) cells offer potential solutions due to their lower alloreactivity.

Additionally, stem cell technology, utilizing induced pluripotent stem cells (iPSCs), enables standardized and scalable production of engineered CAR-T cells. Clinical trials evaluating these strategies, such as UCART19 and CTX110, demonstrate promising results in preventing GvHD while maintaining anti-tumor efficacy.

The review also addresses manufacturing considerations for allogeneic cell products and the challenges in translating preclinical findings into clinical success. By addressing these challenges, allogeneic cell-based immunotherapy continues to advance, paving the way for more accessible, scalable, and effective cancer treatments.

论文信息

作者
Lyu Z、Niu S、Fang Y、Chen Y、Li YR、Yang L
第一作者单位
Department of Microbiology, Immunology & Molecular Genetics, University of California, Los Angeles, CA, 90095, USA.United States
通讯作者单位
Department of Microbiology, Immunology & Molecular Genetics, University of California, Los Angeles, CA, 90095, USA. liliyang@ucla.edu.United States
文献类型
综述
期刊
Experimental hematology & oncology2025 May 2
原文标识
PubMed 40317083 · DOI 10.1186/s40164-025-00654-3