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引用次数: 0
摘要
综述的目的:血液肿瘤学的最新进展开创了利用嵌合抗原受体(CAR)T 细胞通过细胞介导消除病理性 B 细胞群的方法。在这篇综述中,我们讨论了最近采用 CAR-T 治疗严重难治性自身免疫性疾病的情况。我们强调了自身免疫模型的独特之处,并回顾了目前治疗风湿病的临床数据:迄今为止,美国食品及药物管理局(FDA)已批准几种CAR-T用于治疗多发性骨髓瘤和B细胞恶性肿瘤,并已在难治性疾病中显示出非凡的临床反应。由于认识到 B 细胞在某些自身免疫性疾病中的核心作用,CAR-T 目前正被用于实现无药缓解诱导,并有可能治愈多种风湿性疾病。埃尔兰根大学医院的研究小组早先成功用 CD19-CAR 治疗了一名重症难治性系统性红斑狼疮患者,在此基础上,Mackensen 等人又在一项同情使用计划中招募了五名患者,这是迄今为止自身免疫领域最大规模的治疗。在自体 CD19-CAR T 细胞输注后,他们证明所有五名患者的临床和实验室治疗均在至少 12 个月内无药物缓解,并重建了表达天真表型的 B 细胞。摘要:CAR-T 治疗已在重症狼疮和其他自身免疫性疾病中显示出惊人的无药物反应,因此需要进一步探索和开发。
Chimeric antigen receptors: "CARs" in the fast lane for rheumatology.
Purpose of review: Recent advances in hematology-oncology have pioneered cell-mediated elimination of pathologic B-cell populations employing chimeric antigen receptor (CAR) T cells. In this review, we discuss recent adoption of CAR-T treatment for severe refractory autoimmune disease. We highlight unique aspects of the autoimmune model and review current clinical data regarding treatment of rheumatologic disease.
Recent findings: To date, several CAR-Ts are FDA approved for Multiple Myeloma and B-cell malignancies and have demonstrated extraordinary clinical responses in refractory disease. Realizing the central role of B-cells in certain autoimmune diseases, CAR-T is now being explored for achieving drug-free remission induction, and potentially cure, of several rheumatologic diseases. The largest experience to date in the field of autoimmunity, building off the University Hospital Erlangen groups' earlier success treating a single patient with CD19-CAR in severe refractory SLE, Mackensen et al. enrolled five patients in a compassionate use program. Following autologous CD19-CAR T infusion, they demonstrated drug-free clinical and laboratory remission for at least 12 months in all five patients, with reconstitution of B cells expressing a naïve phenotype.
Summary: CAR-T treatment has shown striking drug-free responses in severe lupus and other autoimmune diseases, creating a need for further exploration and development.
期刊介绍:
A high impact review journal which boasts an international readership, Current Opinion in Rheumatology offers a broad-based perspective on the most recent and exciting developments within the field of rheumatology. Published bimonthly, each issue features insightful editorials and high quality invited reviews covering two or three key disciplines which include vasculitis syndromes, medical physiology and rheumatic diseases, crystal deposition diseases and rheumatoid arthritis. Each discipline introduces world renowned guest editors to ensure the journal is at the forefront of knowledge development and delivers balanced, expert assessments of advances from the previous year.