Jose Maria Cabrera-Maqueda, Maria Sepulveda, Raquel Ruiz García, Guillermo Muñoz-Sánchez, Nuria Martínez-Cibrian, Valentín Ortíz-Maldonado, Daniel Lorca-Arce, Mar Guasp, Sara Llufriu, Eugenia Martinez-Hernandez, Thais Armangue, Elianet G Fonseca, María Teresa Alba-Isasi, Julio Delgado, Josep Dalmau, Manel Juan, Albert Saiz, Yolanda Blanco
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We report a patient with refractory MOGAD treated with CD19-directed CAR T-cells.</p><p><strong>Methods: </strong>CD19-directed CAR T-cells (ARI-0001) were produced in-house by lentiviral transduction of autologous fresh leukapheresis and infused after a conventional lymphodepleting regimen.</p><p><strong>Results: </strong>A 18-year-old man developed 2 episodes of myelitis associated with serum MOG-IgG, which were followed by 6 episodes of left optic neuritis (ON) and sustained the presence of MOG-IgG over 6 years despite multiple immunotherapies. After the sixth episode of ON, accompanied by severe residual visual deficits, CAR T-cell treatment was provided without complications. Follow-up of cell counts showed complete depletion of CD19<sup>+</sup> B cells at day +7; reconstituted B cells at day +141 showing a naïve B-cell phenotype, and low or absent memory B cells and plasmablasts for 1 year. MOG-IgG titers have remained undetectable since CAR T-cell infusion. The patient had an early episode of left ON at day +29, when MOG-IgG was already negative, and since then he has remained free of relapses without immunotherapy for 1 year.</p><p><strong>Discussion: </strong>This clinical case shows that CD19-directed CAR T-cell therapy is well-tolerated and is a potential treatment for patients with refractory MOGAD.</p><p><strong>Classification of evidence: </strong>This provides Class IV evidence. 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引用次数: 0
摘要
目的：对于 MOG 抗体相关疾病（MOGAD），预防复发和治疗难治性症状的方法尚不清楚。我们报告了一名接受 CD19 导向 CAR T 细胞治疗的难治性 MOGAD 患者：CD19定向CAR T细胞（ARI-0001）是通过慢病毒转导自体新鲜白细胞产生的，并在常规淋巴清除疗法后输注：一名 18 岁的男子两次患上脊髓炎并伴有血清 MOG-IgG，之后又患上 6 次左侧视神经炎（ON），尽管接受了多种免疫疗法，但 MOG-IgG 的存在持续了 6 年之久。在第六次视神经炎发作并伴有严重的残余视力障碍后，患者接受了CAR T细胞治疗，未出现并发症。细胞计数随访显示，CD19+ B细胞在+7天时完全耗竭；+141天时重组的B细胞显示出幼稚B细胞表型，1年内记忆B细胞和浆细胞数量较少或消失。自 CAR T 细胞输注后，MOG-IgG 滴度一直未检测到。患者在第 +29 天早期出现左侧ON，当时MOG-IgG已呈阴性，此后1年未接受免疫治疗，一直未复发：本临床病例表明，CD19导向的CAR T细胞疗法耐受性良好，是难治性MOGAD患者的一种潜在治疗方法：本研究提供了IV级证据。这是一项没有对照的单项观察性研究。
CD19-Directed CAR T-Cells in a Patient With Refractory MOGAD: Clinical and Immunologic Follow-Up for 1 Year.
Objectives: In MOG antibody-associated disease (MOGAD), relapse prevention and the treatment approach to refractory symptoms are unknown. We report a patient with refractory MOGAD treated with CD19-directed CAR T-cells.
Methods: CD19-directed CAR T-cells (ARI-0001) were produced in-house by lentiviral transduction of autologous fresh leukapheresis and infused after a conventional lymphodepleting regimen.
Results: A 18-year-old man developed 2 episodes of myelitis associated with serum MOG-IgG, which were followed by 6 episodes of left optic neuritis (ON) and sustained the presence of MOG-IgG over 6 years despite multiple immunotherapies. After the sixth episode of ON, accompanied by severe residual visual deficits, CAR T-cell treatment was provided without complications. Follow-up of cell counts showed complete depletion of CD19+ B cells at day +7; reconstituted B cells at day +141 showing a naïve B-cell phenotype, and low or absent memory B cells and plasmablasts for 1 year. MOG-IgG titers have remained undetectable since CAR T-cell infusion. The patient had an early episode of left ON at day +29, when MOG-IgG was already negative, and since then he has remained free of relapses without immunotherapy for 1 year.
Discussion: This clinical case shows that CD19-directed CAR T-cell therapy is well-tolerated and is a potential treatment for patients with refractory MOGAD.
Classification of evidence: This provides Class IV evidence. It is a single observational study without controls.
期刊介绍：
Neurology Neuroimmunology & Neuroinflammation is an official journal of the American Academy of Neurology. Neurology: Neuroimmunology & Neuroinflammation will be the premier peer-reviewed journal in neuroimmunology and neuroinflammation. This journal publishes rigorously peer-reviewed open-access reports of original research and in-depth reviews of topics in neuroimmunology & neuroinflammation, affecting the full range of neurologic diseases including (but not limited to) Alzheimer's disease, Parkinson's disease, ALS, tauopathy, and stroke; multiple sclerosis and NMO; inflammatory peripheral nerve and muscle disease, Guillain-Barré and myasthenia gravis; nervous system infection; paraneoplastic syndromes, noninfectious encephalitides and other antibody-mediated disorders; and psychiatric and neurodevelopmental disorders. Clinical trials, instructive case reports, and small case series will also be featured.
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