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自身免疫性疾病中的嵌合抗原受体T细胞疗法:一个充满前景的前沿领域。

CAR T-cell therapy in autoimmune diseases: a promising frontier on the horizon.

作者信息

Wu Dehong, Xu-Monette Zijun Y, Zhou Jia, Yang Kepeng, Wang Xinchang, Fan Yongsheng, Young Ken H

机构信息

Division of Hematopathology, Department of Pathology, Duke University Medical Center, Durham, NC, United States.

Department of Rheumatology, The Second Affiliated Hospital of Zhejiang Chinese Medical University, Hangzhou, Zhejiang, China.

出版信息

Front Immunol. 2025 Aug 12;16:1613878. doi: 10.3389/fimmu.2025.1613878. eCollection 2025.

DOI:10.3389/fimmu.2025.1613878
PMID:40873568
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC12378106/
Abstract

Although current treatments for autoimmune diseases can effectively control symptoms, they rarely lead to cures and often require lifelong use, accompanied by considerable adverse effects. This emphasizes the urgent need for more targeted therapies that offer long-term efficacy and curative potential. Chimeric antigen receptor (CAR) T-cell therapy presents a promising option by specifically targeting and eliminating autoreactive B cells, with the potential to reset the patient's immune system and promote long-term immune balance. Originally developed for treating hematologic malignancies, where it has achieved remarkable success, recent studies have demonstrated substantial promise of CAR T-cell therapy, such as systemic lupus erythematosus (SLE) and myasthenia gravis. This article provides an overview of the current progress in CAR T-cell therapy for autoimmune diseases, focusing on five key approaches: CD19-targeted CAR T cells, CAR T cells targeting long-lived plasma cells, CAR T cells targeting specific autoantibodies, organ-specific CAR regulatory T cells (Treg cells), and mRNA-engineered CAR T cells. Additionally, this article discusses strategies for optimizing CAR T-cell therapy, including "off-the-shelf" allogeneic CAR T-cell therapy, combined CAR T-cell therapy, establishing timely consensus guidelines for their application in autoimmune diseases, and risk stratification strategies aimed at enhancing the personalization of treatments and minimizing adverse effects. While current research results are promising, further large-scale clinical trials and long-term follow-up are essential to thoroughly evaluate the safety and efficacy of CAR T-cell therapy in autoimmune diseases.

摘要

尽管目前针对自身免疫性疾病的治疗方法可以有效控制症状,但它们很少能治愈疾病,而且通常需要终身使用,同时伴有相当大的副作用。这凸显了迫切需要更具针对性的疗法,以提供长期疗效和治愈潜力。嵌合抗原受体(CAR)T细胞疗法通过特异性靶向和消除自身反应性B细胞,为重置患者免疫系统和促进长期免疫平衡提供了一个有前景的选择。CAR T细胞疗法最初是为治疗血液系统恶性肿瘤而开发的,并在该领域取得了显著成功,最近的研究表明其在系统性红斑狼疮(SLE)和重症肌无力等自身免疫性疾病中也具有巨大潜力。本文概述了CAR T细胞疗法在自身免疫性疾病治疗方面的当前进展,重点介绍了五种关键方法:靶向CD19的CAR T细胞、靶向长寿浆细胞的CAR T细胞、靶向特定自身抗体的CAR T细胞、器官特异性CAR调节性T细胞(Treg细胞)以及mRNA工程化CAR T细胞。此外,本文还讨论了优化CAR T细胞疗法的策略,包括“现成可用”的同种异体CAR T细胞疗法、联合CAR T细胞疗法、为其在自身免疫性疾病中的应用建立及时的共识指南,以及旨在增强治疗个性化和最小化副作用的风险分层策略。虽然目前的研究结果很有前景,但进一步的大规模临床试验和长期随访对于全面评估CAR T细胞疗法在自身免疫性疾病中的安全性和疗效至关重要。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/454b/12378106/7231eb1bac68/fimmu-16-1613878-g005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/454b/12378106/04c0d369d9fc/fimmu-16-1613878-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/454b/12378106/03d641886b41/fimmu-16-1613878-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/454b/12378106/e382e58d1048/fimmu-16-1613878-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/454b/12378106/db2e91c552c8/fimmu-16-1613878-g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/454b/12378106/7231eb1bac68/fimmu-16-1613878-g005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/454b/12378106/04c0d369d9fc/fimmu-16-1613878-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/454b/12378106/03d641886b41/fimmu-16-1613878-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/454b/12378106/e382e58d1048/fimmu-16-1613878-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/454b/12378106/db2e91c552c8/fimmu-16-1613878-g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/454b/12378106/7231eb1bac68/fimmu-16-1613878-g005.jpg

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Current progress in CRISPR-Cas systems for autoimmune diseases.CRISPR-Cas 系统在自身免疫性疾病中的研究进展。
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