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CAR-T 细胞治疗风湿性疾病:未来将走向何方?

英文原题:CAR T-Cell Therapy for Rheumatic Diseases: What Does the Future Hold?

查看英文原题

CAR T-Cell Therapy for Rheumatic Diseases: What Does the Future Hold?

PubMed 2024/12/29(内容时间) BioDrugs Q1 · IF 8.5(JCR 2025)

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中文摘要

嵌合抗原受体(CAR)T细胞疗法最初成功用于治疗血液系统恶性肿瘤,目前正成为治疗自身免疫性疾病(包括风湿性疾病)的潜在方法。经工程化改造、可靶向并清除自身反应性B细胞的CAR-T 细胞,为管理系统性红斑狼疮(SLE)、系统性硬化症(SSc)和炎性肌病等疾病提供了新思路;在这些疾病中,B细胞在发病机制中发挥关键作用。早期病例报告显示出良好结果:患者病情显著缓解、血清学指标恢复正常,并能够停用传统免疫抑制疗法,这推动了多项临床试验启动。

然而,在慢性炎症性风湿病中应用CAR-T 细胞疗法面临独特挑战,包括患者异质性、细胞因子释放综合征等不良反应风险以及治疗费用高昂。尽管存在这些挑战,CAR-T 细胞为难治性自身免疫病带来长期缓解乃至治愈的潜力十分显著。目前研究旨在优化CAR-T 细胞构建并改善安全性,为其更广泛用于风湿病铺平道路。若能克服这些挑战,CAR-T 细胞疗法有望改变慢性炎症性风湿病的治疗格局,为重症、难治患者带来新的希望。

展开英文摘要原文

Chimeric antigen receptor (CAR) T-cell therapy, initially successful in treating hematological malignancies, is emerging as a potential treatment for autoimmune diseases, including rheumatic conditions. CAR T cells, engineered to target and eliminate autoreactive B cells, offer a novel approach to managing diseases like systemic lupus erythematosus (SLE), systemic sclerosis (SSc), and inflammatory myopathies, where B cells play a pivotal role in disease pathology.

Early case reports have demonstrated promising results, with patients achieving significant disease remission, normalization of serological markers, and the ability to discontinue traditional immunosuppressive therapies, which supported the initiation of several clinical trials.

However, the application of CAR T-cell therapy in chronic inflammatory rheumatic disorders poses unique challenges, including patient heterogeneity, the risk of adverse effects such as cytokine release syndrome, and the high costs associated with the therapy. Despite these challenges, the potential for CAR T cells to provide long-term remission or even a cure in refractory autoimmune diseases is significant.

Ongoing research aims to optimize CAR T-cell constructs and improve safety profiles, paving the way for broader application in rheumatic diseases. If these challenges can be addressed, CAR T-cell therapy could revolutionize the treatment landscape for chronic inflammatory rheumatic disorders, offering new hope for patients with severe, treatment-resistant conditions.

论文信息

作者
Avouac J、Scherlinger M、Club for Innovative Immunotherapies in Immune-Mediated Inflammatory Diseases (C3I)
单位
Service de Rhumatologie, Hôpital Cochin, AP-HP, CUP, Université Paris Descartes, 27 rue du Faubourg Saint-Jacques, 75014, Paris, France. jerome.avouac@aphp.fr.France
文献类型
综述
期刊
BioDrugs : clinical immunotherapeutics, biopharmaceuticals and gene therapy2025 Jan
原文标识
PubMed 39738985 · DOI 10.1007/s40259-024-00692-z