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优化实体瘤 CAR-T 细胞治疗:临床视角

英文原题:Optimizing CAR T cell therapy for solid tumours: a clinical perspective.

查看英文原题

Optimizing CAR T cell therapy for solid tumours: a clinical perspective.

PubMed 2025/10/02(内容时间) Nat Rev Clin Oncol Q1 · IF 94.6(JCR 2025)

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中文摘要

嵌合抗原受体(CAR)T细胞疗法正在革新血液系统恶性肿瘤的治疗,但用于实体瘤仍面临特殊障碍。本综述讨论优化CAR-T 疗法的重要进展,并提供应对这些挑战的临床实践见解。文章介绍的关键策略包括:选择靶抗原以增强疗效并尽量减少靶向肿瘤外正常组织毒性;尽早单采、快速制造并前线应用,以维持T细胞适能并确保及时治疗;通过淋巴细胞清除促进CAR-T 细胞扩增;采用局部区域递送以最大化局部药物浓度并减少全身毒性;以及重复输注以延长治疗作用。此外,我们讨论准确评估CAR-T 疗效所需的先进应答评价框架,并强调需要稳健的毒性管理方法以减轻严重不良事件。本综述系统梳理这些多层面挑战,为优化CAR-T 治疗实体瘤、提高疗效和安全性提供全面指南。

展开英文摘要原文

Chimeric antigen receptor (CAR) T cell therapy is revolutionizing the management of haematological malignancies but faces particular hurdles in the treatment of solid tumours. In this Review, we discuss important advances in refining CAR T cell therapy to provide practical clinical insights to address these challenges.

We describe key strategies, including target antigen selection to enhance efficacy while minimizing on-target, off-tumour toxicities; early apheresis, rapid manufacturing and frontline application to preserve T cell fitness and ensure timely treatment; lymphodepletion to augment CAR T cell expansion; locoregional delivery to maximize local therapeutic concentrations and reduce systemic toxicity; and repeat infusions to prolong therapeutic effects.

Furthermore, we discuss advanced response evaluation frameworks that will be essential for accurate assessment of the efficacy of CAR T cell therapies, and we highlight the need for robust toxicity management approaches to mitigate severe adverse events. By systematically addressing these multifaceted challenges, this Review provides a comprehensive guide for the optimization of CAR T cell therapy for solid tumours to enhance both efficacy and safety.

论文信息

作者
Li J、Liu C、Zhang P、Shen L、Qi C
第一作者单位
Beijing Key Laboratory of Cell and Gene Therapy for Solid Tumors, Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education/Beijing), Department of Gastrointestinal Oncology, Peking University Cancer Hospital & Institute, Beijing, China.China
通讯作者单位
Beijing Key Laboratory of Cell and Gene Therapy for Solid Tumors, State Key Laboratory of Holistic Integrative Management of Gastrointestinal Cancers, Department of Early Drug Development Centre, Peking University Cancer Hospital & Institute, Beijing, China. changsongqi@bjmu.edu.cn.China
文献类型
综述
期刊
Nature reviews. Clinical oncology2025 Dec
原文标识
PubMed 41039013 · DOI 10.1038/s41571-025-01075-1