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用于治疗风湿性疾病的嵌合抗原受体T细胞疗法:未来前景如何?

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

作者信息

Avouac Jérôme, Scherlinger Marc

机构信息

Service de Rhumatologie, Hôpital Cochin, AP-HP, CUP, Université Paris Descartes, 27 rue du Faubourg Saint-Jacques, 75014, Paris, France.

INSERM U1016 and UMR8104, Institut Cochin, 75014, Paris, France.

出版信息

BioDrugs. 2025 Jan;39(1):5-19. doi: 10.1007/s40259-024-00692-z. Epub 2024 Dec 29.

Abstract

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.

摘要

嵌合抗原受体(CAR)T细胞疗法最初在治疗血液系统恶性肿瘤方面取得成功,如今正成为包括风湿性疾病在内的自身免疫性疾病的一种潜在治疗方法。经工程改造以靶向并消除自身反应性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一种新方法,在这些疾病中B细胞在疾病病理过程中起关键作用。早期病例报告显示出了有前景的结果,患者实现了显著的疾病缓解、血清学标志物正常化,并能够停用传统免疫抑制疗法,这支持了多项临床试验的开展。然而,CAR T细胞疗法在慢性炎症性风湿性疾病中的应用带来了独特的挑战,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与该疗法相关的高昂成本。尽管存在这些挑战,CAR T细胞在难治性自身免疫性疾病中实现长期缓解甚至治愈的潜力巨大。正在进行的研究旨在优化CAR T细胞构建体并改善安全性,为在风湿性疾病中更广泛的应用铺平道路。如果这些挑战能够得到解决,CAR T细胞疗法可能会彻底改变慢性炎症性风湿性疾病的治疗格局,为患有严重难治性疾病的患者带来新希望。

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