CAR T-Cell Therapy in Autoimmune Diseases: A Promising Frontier on the Horizon

Dehong Wu^1,2Zijun Y. Xu-Monette²Jia Zhou³Kepeng Yang¹Xinchang Wang¹Yongsheng Fan¹Ken H. Young^2*

• ¹Second Affiliated Hospital, Zhejiang Chinese Medical University, Hangzhou, China
• ²Division of Hematopathology, Department of Pathology, School of Medicine, Duke University, Durham, California, United States
• ³Zhejiang Chinese Medical University, Hangzhou, Zhejiang Province, China

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 the 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, and the importance of establishing timely consensus guidelines for their application in autoimmune diseases. A critical component of the article is the incorporation of 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 this context.