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嵌合抗原受体 (CAR) T 细胞疗法:工程化免疫细胞治疗肝脏疾病

英文原题:Chimeric antigen receptor (CAR) T-cell therapy: Engineering immune cells to treat liver diseases.

查看英文原题

Chimeric antigen receptor (CAR) T-cell therapy: Engineering immune cells to treat liver diseases.

PubMed 2025/06/20(内容时间) J Hepatol Q1 · IF 40.1(JCR 2025)

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中文摘要

内源性T细胞通过人类白细胞抗原(HLA)/肽复合物识别抗原。然而,HLA多态性对开发广泛适用的过继性T细胞疗法构成了重大挑战。工程化T细胞可以通过一种合成的嵌合抗原受体(CAR)绕过这一障碍,该受体具有与细胞内信号基序融合的抗体衍生识别结构域,能够独立于HLA靶向表面抗原。CAR-T 细胞疗法已改变了血液学中B细胞恶性肿瘤的治疗,近期研究还证明了其针对实体瘤的治疗潜力。在本综述中,我们概述了CAR技术的基本原理和关键成就,重点关注其在肝脏病毒感染、自身免疫性肝病和肝胆肿瘤中的应用。我们还重点介绍了针对衰老细胞和肝纤维化的新兴衰老细胞清除疗法,以及旨在在移植中诱导肝脏特异性免疫耐受的调节性CAR-T 细胞。最后,我们讨论了正在进行的和未来的研究,旨在提高基于CAR的疗法作为“活体药物”的特异性、疗效和安全性,以实现对肝脏疾病的靶向、持久和个性化治疗。

展开英文摘要原文

Endogenous T cells recognise antigens through human leukocyte antigen (HLA)/peptide complexes.

However, HLA polymorphism poses a major challenge to the development of broadly applicable adoptive T-cell therapies. Engineered T cells can circumvent this barrier by targeting surface antigens independently from HLA through a synthetic chimeric antigen receptor (CAR) with an antibody-derived recognition domain fused to intracellular signalling motifs.

CAR T-cell therapies have transformed the treatment of B-cell malignancies in haematology, and recent studies demonstrate therapeutic potential against solid tumours. In this review, we provide an overview of the fundamental principles and key achievements of CAR technology, with a focus on its applications in hepatic viral infections, autoimmune liver diseases, and hepatobiliary tumours.

We also highlight emerging senolytic therapies targeting senescent cells and hepatic fibrosis, as well as regulatory CAR T cells designed to induce liver-specific immune tolerance in transplantation.

Finally, we discuss ongoing and future research aimed at improving the specificity, efficacy, and safety of CAR-based therapies as "living drugs" for targeted, durable, and personalised treatment of liver diseases.

论文信息

作者
Jaeckel E、Friedman SL、Hudecek M、Protzer U
第一作者单位
University of Toronto, Center for Liver Transplantation, Center for Islet Transplantation, Multi-Organ Transplant Center, Toronto, Canada.Canada
通讯作者单位
Institute of Virology, School of Medicine and Health, Technical University of Munich / Helmholtz Munich, Germany; German Center for Infection Research (DZIF), Munich partner site, Munich, Germany. Electronic address: protzer@tum.de.Germany
文献类型
综述
期刊
Journal of hepatology2025 Nov
原文标识
PubMed 40545042 · DOI 10.1016/j.jhep.2025.06.007