Infusion of T cells engineered to express chimeric antigen receptors (CARs) that target B cells has proven to be a successful treatment for B cell malignancies. This success inspired the development of CAR T cells to selectively deplete or modulate the aberrant immune responses that underlie autoimmune disease. Promising results are emerging from clinical trials of CAR T cells targeting the B cell protein CD19 in patients with B cell-driven autoimmune diseases. Further approaches are being designed to extend the application and improve safety of CAR T cell therapy in the setting of autoimmunity, including the use of chimeric autoantibody receptors to selectively deplete autoantigen-specific B cells and the use of regulatory T cells engineered to express antigen-specific CARs for targeted immune modulation. Here, we highlight important considerations, such as optimal target cell populations, CAR construct design, acceptable toxicities and potential for lasting immune reset, that will inform the eventual safe adoption of CAR T cell therapy for the treatment of autoimmune diseases.

事实证明，输注经工程改造可表达靶向 B 细胞的嵌合抗原受体 (CAR) 的 T 细胞是治疗 B 细胞恶性肿瘤的成功方法。这一成功激发了 CAR T 细胞的开发，以选择性地消除或调节自身免疫性疾病的异常免疫反应。针对 B 细胞蛋白 CD19 的 CAR T 细胞在 B 细胞驱动的自身免疫性疾病患者中的临床试验正在取得有希望的结果。正在设计进一步的方法来扩展 CAR T 细胞疗法在自身免疫性疾病中的应用并提高其安全性，包括使用嵌合自身抗体受体选择性地消耗自身抗原特异性 B 细胞，以及使用经过改造的调节性 T 细胞来表达抗原。用于靶向免疫调节的特定 CAR。在这里，我们强调重要的考虑因素，例如最佳靶细胞群、CAR 构建设计、可接受的毒性和持久免疫重置的潜力，这将为最终安全采用 CAR T 细胞疗法治疗自身免疫性疾病提供信息。