CD19 靶向 CAR T 细胞治疗难治性 MOGAD：1 年的临床和免疫随访。
CD19-Directed CAR T-Cells in a Patient With Refractory MOGAD: Clinical and Immunologic Follow-Up for 1 Year.
机构信息
From the Neuroimmunology and Multiple Sclerosis Unit (J.M.C.-M., M.S., R.R.G., M.G., S.L., E.M.-H., T.A., E.G.F., M.T.A.-I., A.S., Y.B.), Service of Neurology, Hospital Clinic de Barcelona, and Universitat de Barcelona; Neuroimmunology Program (J.M.C.-M., M.S., R.R.G., M.G., S.L., E.M.-H., T.A., E.G.F., M.T.A.-I., J.D., A.S., Y.B.), Fundació de Recerca Clínic Barcelona- Institut d'Investigacions Biomèdiques August Pi i Sunyer; Department of Immunology (R.R.G., G.M.-S., D.L.-A., M.J.), Hospital Clínic de Barcelona, Fundació de Recerca Clínic Barcelona-Institut d'Investigacions Biomèdiques August Pi i Sunyer, Universitat de Barcelona; Department of Hematology (N.M.-C., V.O.-M., J.D.), Hospital Clínic de Barcelona; Institut d'Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS); Pediatric Neuroimmunology Unit (T.A.), Department of Neurology, Sant Joan de Déu (SJD) Children's Hospital, University of Barcelona; Centro de Investigación Biomédica en Red de Cáncer (CIBERONC) (J.D.); University of Barcelona; Caixa Research Institute (J.D.), Barcelona; and Joint Platform for Immunotherapy of Sant Joan de Deu - Hospital Clinic de Barcelona (M.J.), Spain.
出版信息
Neurol Neuroimmunol Neuroinflamm. 2024 Sep;11(5):e200292. doi: 10.1212/NXI.0000000000200292. Epub 2024 Aug 6.
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.
目的
在髓鞘少突胶质细胞糖蛋白（MOG）抗体相关疾病（MOGAD）中，尚不清楚预防复发和治疗难治性症状的方法。我们报告了一例使用 CD19 定向嵌合抗原受体 T 细胞（CAR T 细胞）治疗难治性 MOGAD 的患者。
方法
通过慢病毒转导自体新鲜白细胞分离物，在常规淋巴耗竭方案后，进行 CD19 定向 CAR T 细胞（ARI-0001）的体内生产，并进行输注。
结果
一名 18 岁男性出现了 2 次与血清 MOG-IgG 相关的脊髓炎，随后发生了 6 次左侧视神经炎（ON），并且在 6 年多的时间里尽管进行了多种免疫治疗，但仍持续存在 MOG-IgG。在第 6 次 ON 发作后，伴有严重的残留视力缺损，在没有并发症的情况下给予 CAR T 细胞治疗。细胞计数的随访显示，CD19 B 细胞在第+7 天完全耗竭；在第+141 天重建的 B 细胞表现出幼稚 B 细胞表型，并且在 1 年内记忆 B 细胞和浆母细胞低或缺失。自 CAR T 细胞输注以来，MOG-IgG 滴度一直无法检测到。在第+29 天，患者出现左侧 ON 的早期发作，此时 MOG-IgG 已经为阴性，此后他在没有免疫治疗的情况下，1 年内未再复发。
讨论
本临床病例表明，CD19 定向 CAR T 细胞治疗是耐受良好的，并且是治疗难治性 MOGAD 患者的一种潜在治疗方法。
证据分类
这提供了 IV 级证据。这是一项没有对照的单中心观察性研究。
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