Graduate School of Peking Union Medical College; Department of Rheumatology, Beijing Hospital, National Center of Gerontology, Institute of Geriatric Medicine; State Key Laboratory of Complex Severe and Rare Diseases, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, 100730, China.
State Key Laboratory of Complex Severe and Rare Diseases, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences, Beijing, 100730, China.
Sci China Life Sci. 2023 Apr;66(4):711-728. doi: 10.1007/s11427-022-2212-5. Epub 2022 Nov 4.
The development of chimeric antigen receptor (CAR)-based therapeutic interventions represented a breakthrough in cancer treatment. Following the success of the CAR-T-cell strategy, this novel therapeutic approach has been applied to other diseases, including autoimmune diseases. Using CAR-T cells to deplete pathological immune cells (i.e., B cells, autoreactive B or T cells, and accessory antigen-presenting cells (APCs)) has resulted in favorable outcomes in diseases characterized by excessive autoantibody levels or hyperactive lymphocyte cell numbers. The importance of immunosuppressive regulatory T cells (Tregs) in restoring immune tolerance has been well established, and CAR-Tregs have shown promising therapeutic potential in treating autoimmune diseases. Moreover, prior experience from the cancer field has provided sufficient paradigms for understanding how to optimize the structure and function of CARs to improve their function, persistence, stability and safety. In this review, we describe the potential application of CAR-T cells and CAR-Tregs in the treatment of autoimmune diseases, and we summarize the currently available strategies of gene editing and synthetic biological tools that have improved the practical application of CAR-based therapies.
嵌合抗原受体 (CAR) 为基础的治疗干预的发展代表了癌症治疗的突破。继 CAR-T 细胞策略成功之后,这种新的治疗方法已应用于其他疾病,包括自身免疫性疾病。使用 CAR-T 细胞清除病理性免疫细胞(即 B 细胞、自身反应性 B 或 T 细胞和辅助抗原呈递细胞 (APCs))已导致在抗体水平过高或淋巴细胞数量异常活跃的疾病中取得良好的效果。免疫抑制调节性 T 细胞 (Treg) 在恢复免疫耐受方面的重要性已得到充分证实,CAR-Treg 在治疗自身免疫性疾病方面显示出有希望的治疗潜力。此外,来自癌症领域的先前经验为理解如何优化 CAR 的结构和功能以提高其功能、持久性、稳定性和安全性提供了充分的范例。在这篇综述中,我们描述了 CAR-T 细胞和 CAR-Treg 在治疗自身免疫性疾病中的潜在应用,并总结了目前可用的基因编辑和合成生物学工具策略,这些策略提高了基于 CAR 的治疗的实际应用。