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风湿性疾病中的 CAR-T 细胞治疗:一篇综述

英文原题:CAR-T cell therapy in rheumatic diseases: a review article.

查看英文原题

CAR-T cell therapy in rheumatic diseases: a review article.

PubMed 2025/04/26(内容时间) Clin Rheumatol Q3 · IF 2.7(JCR 2025)

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中文摘要

CAR-T 细胞疗法最初为治疗血液系统恶性肿瘤而开发,是一种创新的免疫调节疗法,目前也被视为自身免疫病和风湿性疾病的潜在治疗方法。该方法通过基因工程使T细胞表达嵌合抗原受体(CAR),从而靶向致病免疫细胞相关特定抗原。本综述讨论CAR-T 治疗系统性红斑狼疮(SLE)、类风湿关节炎(RA)和系统性硬化症(SSc)等自身免疫病的可能性。在SLE研究中,CAR-T 可通过靶向疾病过程中的自身反应性B细胞维持缓解,是其重要作用之一。在难治性RA中,CAR-T 也显示出选择性杀伤驱动疾病的免疫细胞的潜在治疗作用。对于SSc,CAR-T 可能代表一种新疗法,因为其可靶向B细胞失调及驱动疾病病理的纤维化过程。新证据提示CAR-T 还可能用于干燥综合征和皮肌炎等疾病。CAR-T 疗法具有精准、持久及可能实现长期缓解的前景,但仍面临细胞因子释放综合征、免疫毒性和治疗可负担性等问题。开发CAR调节性T细胞(CAR-Treg)及先进基因编辑技术有望提高疗法特异性和安全性。

此外,还需开展临床试验及长期研究,以确立这一创新方法的疗效、安全性和经济可行性。本综述强调了CAR-T 疗法管理风湿性疾病、尤其难治性病例的变革潜力。CAR-T 可实现靶向免疫调节,并尽量减少全身免疫抑制,有望重塑治疗模式并改善自身免疫病结局。

展开英文摘要原文

CAR-T cell therapy, a pioneering immune-modulating treatment that was initially designed for hematologic malignancies, is now being considered a potential treatment for autoimmune and rheumatic diseases. This method involves genetically engineering T cells to express chimeric antigen receptors (CARs), allowing them to target specific antigens associated with pathogenic immune cells. The review covers the possibility of CAR-T therapy in the treatment of autoimmune diseases like systemic lupus erythematosus (SLE), rheumatoid arthritis (RA), systemic sclerosis (SSc). The therapy's ability to maintain remission by targeting autoreactive B cells in the course of disease has been an important aspect of studies involving SLE.

In refractory RA, CAR-T cells also demonstrate a potential therapeutic modality in selectively killing immune cells driving the disease process. For SSc, CAR-T therapy may represent a novel therapeutic approach because it targets the dysregulated activity of B cells as well as the fibrotic processes that drive the disease pathology.

Emerging evidence suggests potential applications in conditions such as Sj gren's syndrome and dermatomyositis. While CAR-T therapy promises accuracy, persistence, and the potential for long-term remission, many problems remain, including the risk of cytokine release syndrome, immune toxicity, and treatment affordability. The development of CAR-Tregs and advanced gene-editing techniques may increase the specificity and safety of therapy.

In addition, clinical trials and long-term studies should be conducted to establish the efficacy, safety, and economic feasibility of this innovative approach. This review underscores the transformative potential of CAR-T therapy in the management of rheumatic diseases, particularly in refractory cases. Offering targeted immunomodulation with a minimum of systemic immune suppression, CAR-T therapy could redefine therapeutic paradigms and offer hope for improved outcomes in autoimmune diseases.

论文信息

作者
Patil H、Bharadwaj RK、Dutta N、Subramanian R、Prasad S、Mamadapur M
第一作者单位
Department of Pharmacy Practice, JSS College of Pharmacy, Mysuru, India.India
通讯作者单位
Department of Clinical Immunology and Rheumatology, JSS Medical College, JSS Academy of Higher Education and Research, Mysuru, India. mahabaleshwarm@jssuni.edu.in.India
文献类型
综述
期刊
Clinical rheumatology2026 Feb
原文标识
PubMed 40285991 · DOI 10.1007/s10067-025-07451-7