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用自体 CD19 靶向嵌合抗原受体 T 细胞治疗合并重症肌无力和 Lambert-Eaton 肌无力综合征。

Treatment of concomitant myasthenia gravis and Lambert-Eaton myasthenic syndrome with autologous CD19-targeted CAR T cells.

机构信息

Department of Neurology, St. Josef-Hospital Bochum, Ruhr-University Bochum, 44791 Bochum, Germany.

Department of Hematology and Oncology, Ruhr-University Bochum, Knappschaftskrankenhaus, 44892 Bochum, Germany.

出版信息

Neuron. 2024 Jun 5;112(11):1757-1763.e2. doi: 10.1016/j.neuron.2024.04.014. Epub 2024 May 1.

Abstract

Myasthenia gravis (MG) and Lambert-Eaton myasthenic syndrome (LEMS) are autoimmune disorders affecting neuromuscular transmission. Their combined occurrence is rare, and treatment remains challenging. Two women diagnosed with concomitant MG/LEMS experienced severe, increasing disease activity despite multiple immunotherapies. Anti-CD19 chimeric antigen receptor (CAR) T cells have shown promise for treating autoimmune diseases. This report details the safe application of anti-CD19 CAR T cells for treating concomitant MG/LEMS. After CAR T cell therapy, both patients experienced rapid clinical recovery and regained full mobility. Deep B cell depletion and normalization of acetylcholine receptor and voltage-gated calcium channel N-type autoantibody levels paralleled major neurological responses. Within 2 months, both patients returned to everyday life, from wheelchair dependency to bicycling and mountain hiking, and remain stable at 6 and 4 months post-CAR T cell infusion, respectively. This report highlights the potential for anti-CD19 CAR T cells to achieve profound clinical effects in the treatment of neuroimmunological diseases.

摘要

重症肌无力(MG)和 Lambert-Eaton 肌无力综合征(LEMS)是影响神经肌肉传递的自身免疫性疾病。它们同时发生的情况很少见,治疗仍然具有挑战性。两名被诊断患有合并 MG/LEMS 的女性尽管接受了多种免疫治疗,但疾病活动仍严重且不断加重。抗 CD19 嵌合抗原受体(CAR)T 细胞在治疗自身免疫性疾病方面显示出前景。本报告详细介绍了抗 CD19 CAR T 细胞治疗合并 MG/LEMS 的安全性。CAR T 细胞治疗后,两名患者均迅速临床康复并恢复了完全活动能力。深度 B 细胞耗竭和乙酰胆碱受体及电压门控钙通道 N 型自身抗体水平的正常化与主要神经反应平行。在 2 个月内,两名患者分别从轮椅依赖恢复到骑自行车和登山,生活恢复正常,并且在 CAR T 细胞输注后分别稳定 6 个月和 4 个月。本报告强调了抗 CD19 CAR T 细胞在治疗神经免疫性疾病方面实现深刻临床效果的潜力。

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