Anti-CD19 CAR-T cells are effective in severe idiopathic Lambert-Eaton myasthenic syndrome.

IF 11.7 1区 医学 Q1 CELL BIOLOGY
Jonathan Wickel, Ulf Schnetzke, Anne Sayer-Klink, Jenny Rinke, Dominic Borie, Diana Dudziak, Andreas Hochhaus, Lukas Heger, Christian Geis
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引用次数: 0

Abstract

Lambert-Eaton myasthenic syndrome (LEMS) is an autoantibody-mediated disease of the neuromuscular junction characterized by muscular weakness. Autoantibodies to presynaptic P/Q-type voltage-gated calcium channels (VGCCs) induce defective neuromuscular function. In severe cases, current immunosuppressive and immunomodulatory treatment strategies are often insufficient. First reports show beneficial effects of anti-CD19 chimeric antigen receptor (CAR)-T cell therapy in patients with autoantibody-mediated myasthenia gravis. We report a patient with isolated idiopathic LEMS treated with autologous anti-CD19-CAR-T cells. In this patient, CAR-T infusion leads to expansion of predominantly CD4+ CAR-T cells with a terminally differentiated effector memory cells re-expressing CD45RA (TEMRA)-like phenotype indicating cytotoxic capabilities and subsequent B cell depletion. VGCC antibody titers decrease, resulting in a clinical improvement of LEMS symptoms, e.g., 8-fold increase in walking distance. The patient does not show relevant side effects except for cytokine release syndrome grade 2 and intermittent neutropenia suggesting that anti-CD19 CAR-T cell therapy may be a treatment option in patients with LEMS.

抗 CD19 CAR-T 细胞对重症特发性兰伯特-伊顿肌萎缩综合征有效。
兰伯特-伊顿肌萎缩综合征(LEMS)是一种由自身抗体介导的神经肌肉接头疾病,以肌肉无力为特征。突触前 P/Q 型电压门控钙通道(VGCC)的自身抗体会导致神经肌肉功能缺陷。在严重病例中,目前的免疫抑制和免疫调节治疗策略往往是不够的。首次报道显示,抗 CD19 嵌合抗原受体(CAR)-T 细胞疗法对自身抗体介导的重症肌无力患者有良好疗效。我们报告了一名接受自体抗CD19-CAR-T细胞治疗的孤立性特发性LEMS患者。在这名患者身上,CAR-T 输注导致主要为 CD4+ 的 CAR-T 细胞扩增,这些细胞具有重新表达 CD45RA(TEMRA)的终末分化效应记忆细胞样表型,显示出细胞毒性能力,并随后导致 B 细胞耗竭。VGCC 抗体滴度下降,导致 LEMS 症状得到临床改善,例如步行距离增加了 8 倍。除了细胞因子释放综合征 2 级和间歇性中性粒细胞减少症外,患者没有出现相关副作用,这表明抗 CD19 CAR-T 细胞疗法可能是 LEMS 患者的一种治疗选择。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
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来源期刊
Cell Reports Medicine
Cell Reports Medicine Biochemistry, Genetics and Molecular Biology-Biochemistry, Genetics and Molecular Biology (all)
CiteScore
15.00
自引率
1.40%
发文量
231
审稿时长
40 days
期刊介绍: Cell Reports Medicine is an esteemed open-access journal by Cell Press that publishes groundbreaking research in translational and clinical biomedical sciences, influencing human health and medicine. Our journal ensures wide visibility and accessibility, reaching scientists and clinicians across various medical disciplines. We publish original research that spans from intriguing human biology concepts to all aspects of clinical work. We encourage submissions that introduce innovative ideas, forging new paths in clinical research and practice. We also welcome studies that provide vital information, enhancing our understanding of current standards of care in diagnosis, treatment, and prognosis. This encompasses translational studies, clinical trials (including long-term follow-ups), genomics, biomarker discovery, and technological advancements that contribute to diagnostics, treatment, and healthcare. Additionally, studies based on vertebrate model organisms are within the scope of the journal, as long as they directly relate to human health and disease.
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