CAR-T细胞疗法治疗系统性红斑狼疮：现状与未来展望

CAR-T Cell Therapy for Systemic Lupus Erythematosus: Current Status and Future Prospects

摘要: 系统性红斑狼疮(SLE)是一种慢性自身免疫性疾病，其特征为多系统受累和临床表现多样，主要影响育龄女性。尽管抗疟疾药物、糖皮质激素和免疫抑制剂等传统治疗方法取得了进展，但许多患者仍存在难治性或药物不耐受的情况。嵌合抗原受体(CAR) T细胞疗法在血液系统恶性肿瘤的治疗中取得了革命性进展，最近已成为自身免疫性疾病的一种有前景的治疗方法。本综述全面审视了CAR-T疗法在SLE中的现有证据，重点关注其作用机制、临床疗效、安全性特征和潜在局限性。文章讨论了早期临床病例中观察到的疾病迅速缓解、自身反应性B细胞的持续耗竭以及随后免疫耐受的重建。此外，文章还探讨了诸如体内CAR-T生成和替代细胞平台等创新策略，这些策略可能提高可及性并降低成本。尽管在长期安全性、患者选择和治疗可及性方面仍存在诸多挑战，但嵌合抗原受体T细胞(CAR-T)疗法在难治性系统性红斑狼疮(SLE)的治疗中代表着一种范式转变，有可能为治疗选择有限的患者提供持续的无药缓解。

Abstract: Systemic lupus erythematosus (SLE) is a chronic autoimmune disease characterized by multi-system involvement and diverse clinical manifestations, mainly affecting women of childbearing age. Despite the progress made in traditional treatments such as antimalarial drugs, glucocorticoids, and immunosuppressants, many patients still have refractory or drug intolerance conditions. Chimeric antigen receptor (CAR) T-cell therapy has made revolutionary progress in the treatment of hematological malignancies and has recently emerged as a promising treatment for autoimmune diseases. This review comprehensively examines the existing evidence of CAR-T therapy in SLE, focusing on its mechanism of action, clinical efficacy, safety profile, and potential limitations. The article discusses the rapid disease remission observed in early clinical cases, the sustained depletion of autoreactive B cells, and the subsequent re-establishment of immune tolerance. Additionally, it explores innovative strategies such as in vivo CAR-T generation and alternative cell platforms, which may enhance accessibility and reduce costs. Despite numerous challenges in long-term safety, patient selection, and treatment accessibility, CAR-T cell therapy represents a paradigm shift in the treatment of refractory SLE and has the potential to provide sustained drug-free remission for patients with limited treatment options.