《生命科学》 2026, 38(4): 645-650

CAR-T细胞治疗自身免疫性疾病进展

张晨星¹ , 殷 蕾¹ , 茅幼英^1,2,*

¹上海交通大学医学院附属上海儿童医学中心肾脏科，上海 200127 ²上海交通大学医学院附属松江医院 儿科，上海 201600

摘　要：

嵌合抗原受体T细胞（CAR-T）疗法已在肿瘤免疫治疗中取得了显著成果。随着CAR-T细胞疗法的不断发展，其研究领域逐渐扩展至自身免疫性疾病。本文综述了CAR-T细胞的结构及分类、CAR-T细胞治疗流程和不良反应及其在自身免疫性疾病治疗中的研究进展和目前面临的问题和挑战。目前CAR-T细胞治疗已在多种自身免疫性疾病中成功应用，并显示出良好的疗效。尽管CAR-T细胞治疗使某些难治性患者达到长期无药缓解，为自身免疫性疾病治疗提供了新的方向，目前仍需大规模的临床研究来验证其长期疗效和安全性。

通讯作者：茅幼英 , Email:maoyouying2012@163.com

Advances of chimeric antigen receptor T cell (CAR-T) therapy for autoimmune diseases

ZHANG Chen-Xing¹ , YIN Lei¹ , MAO You-Ying^1,2,*

¹Nephrology Department, Shanghai Children’s Medical Center, Shanghai Jiao Tong University School of Medicine, Shanghai 200127, China ²Pediatrics Department, Songjiang Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 201600, China

Abstract:

Chimeric antigen receptor T cell (CAR-T) therapy has emerged as a transformative immunotherapeutic strategy with groundbreaking success in B-cell malignancies. In recent years, this powerful approach has been rapidly extended to autoimmune diseases, where autoreactive B cells play a central pathogenic role by producing autoantibodies, presenting autoantigens, and promoting chronic inflammation. Conventional treatments, including immunosuppressants and B-celldepleting antibodies, often fail to induce sustained remission in refractory cases due to incomplete elimination of pathological B cells in lymphoid organs and inflamed tissues. This review comprehensively summarizes the structural design, generational evolution, clinical workflow, safety profiles, recent advances, and remaining challenges of CAR-T therapy for autoimmune diseases. CAR-T cells are engineered to target B-cell-restricted antigens such as CD19, CD20, and CD22 in an MHC independent manner, enabling specific and efficient clearance of autoreactive B cells. To date, five generations of CAR constructs have been developed, and fifth-generation universal allogeneic CAR-T cells represent a major breakthrough by offering offtheshelf availability, reduced manufacturing time, and lower costs. The standard clinical pipeline encompasses patient eligibility assessment, apheresis, T-cell isolation and genetic modification, ex vivo expansion, lymphodepletion chemotherapy, CAR-T infusion, intensive monitoring for adverse events, efficacy evaluation, and long-term follow-up. The primary adverse reactions are cytokine release syndrome (CRS) and immune effector cell-associated neurotoxicity syndrome (ICANS), which are mostly manageable with timely intervention. Promising clinical data have demonstrated that CD19-targeted CAR-T therapy can induce durable drug-free remission in refractory systemic lupus erythematosus, idiopathic inflammatory myositis, and systemic sclerosis. Nevertheless, several critical challenges persist, including impaired quantity and function of autologous T cells in heavily pretreated patients, potential amplification of autoreactive T-cell clones, high production costs, and insufficient long-term safety and efficacy data. Future investigations should focus on optimizing CAR structure, developing safer universal cell products, establishing standardized protocols, and conducting large-scale multicenter clinical trials to advance CAR-T therapy into a mainstream curative option for refractory autoimmune diseases.

Communication Author：MAO You-Ying , Email:maoyouying2012@163.com