Depatment of Internal Medicine, Yale New-Haven Hospital, Yale School of Medicine.
Section of Rheumatology, Allergy & Immunology, Department of Internal Medicine, Yale School of Medicine, New Haven Conn.
Curr Opin Rheumatol. 2024 May 1;36(3):176-183. doi: 10.1097/BOR.0000000000001012. Epub 2024 Mar 26.
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.
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.
CAR-T treatment has shown striking drug-free responses in severe lupus and other autoimmune diseases, creating a need for further exploration and development.
目的综述：血液肿瘤学的最新进展开创了利用嵌合抗原受体 (CAR) T 细胞介导消除病理性 B 细胞群体的方法。在这篇综述中，我们讨论了 CAR-T 治疗严重难治性自身免疫性疾病的最新应用。我们强调了自身免疫模型的独特方面，并回顾了目前关于治疗风湿性疾病的临床数据。
最近的发现：迄今为止，已有几种 CAR-T 药物获得美国食品和药物管理局 (FDA) 批准用于多发性骨髓瘤和 B 细胞恶性肿瘤，并在难治性疾病中显示出非凡的临床反应。鉴于 B 细胞在某些自身免疫性疾病中的核心作用，CAR-T 现在正被探索用于实现某些风湿性疾病的无药物缓解诱导和潜在治愈。该领域迄今为止最大的自身免疫经验是在埃尔兰根大学医院 (University Hospital Erlangen) 小组早期成功治疗一名严重难治性系统性红斑狼疮 (SLE) 患者的单个 CD19-CAR 的基础上进行的，Mackensen 等人开展了一项同情使用计划，入组了 5 名患者。在接受自体 CD19-CAR T 输注后，所有 5 名患者均至少在 12 个月内达到无药物的临床和实验室缓解，且 B 细胞表达幼稚表型。
总结：CAR-T 治疗在严重狼疮和其他自身免疫性疾病中显示出显著的无药物反应，这需要进一步探索和开发。
