Chimeric antigen receptor T cells in treatment-refractory DAGLA antibody-associated encephalitis.

IF 11.8 Q1 MEDICINE, RESEARCH & EXPERIMENTAL

Med Pub Date : 2025-09-12 Epub Date: 2025-07-23 DOI:10.1016/j.medj.2025.100776

Tobias Hegelmaier, Denise Wolleschak, Vaia Pappa, Jonathan Wickel, Christian Geis, Ramona Miske, Alexander Duscha, Christiane Desel, Martin Böttcher, Alexandra Neyazi, Simon Faissner, Jeremias Motte, Ralf Gold, Dominic Borie, Georg Schett, Dimitrios Mougiakakos, Aiden Haghikia

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引用次数: 0

Abstract

Background: Autoimmune encephalitides are a heterogeneous group of autoantibody-associated central nervous system disorders. The clinical course of autoimmune encephalitides can be life threatening, and treatment can be challenging.

Objective: This report describes a case of treatment-refractory, anti-diacylglycerol lipase alpha (DAGLA) antibody-associated autoimmune encephalitis successfully treated with chimeric antigen receptor (CAR) T cells.

Methods: Treatment was done by single intravenous infusion of fully human, second-generation CAR T cells (KYV-101) targeting CD19 and depleting B cells. Clinical response was measured by International Cooperative Ataxia Rating Scale and Clinical Assessment Scale in Autoimmune Encephalitis scores. Autoantibodies against DAGLA were measured by a recombinant cell-based indirect immunofluorescence assay in the serum and the cerebrospinal fluid and confirmed by staining of primary murine neurons and brain sections.

Findings: A 36-year-old man developed rapidly progressing generalized myoclonus, cerebellar head tremor, vertical binocular nystagmus, and tetraparesis despite treatment with pulse glucocorticoid therapy, plasma exchange, and rituximab. Anti-DAGLA antibodies were positive in the indirect immunofluorescence assay, in serum and cerebrospinal fluid, and reacted with neurons and brain sections. Due to his severe clinical condition and treatment refractoriness, the patient received a single infusion of autologous anti-CD19 CAR T cells. Clinical scores improved significantly after treatment, and anti-DAGLA antibody levels in serum and cerebrospinal fluid diminished. Oligoclonal bands in the cerebrospinal fluid were initially positive and became negative after CAR T cell therapy.

Conclusion: The report highlights the therapeutic potential of anti-CD19 CAR T cell therapy in severe, treatment-refractory autoimmune encephalitis.

Funding: There was no external funding for the treatment or the data generated.

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嵌合抗原受体T细胞治疗难治性DAGLA抗体相关脑炎。

背景：自身免疫性脑炎是一种与自身抗体相关的中枢神经系统疾病。自身免疫性脑炎的临床过程可能危及生命，治疗可能具有挑战性。目的：本报告描述了一例用嵌合抗原受体（CAR） T细胞成功治疗难治性抗二酰基甘油脂肪酶α (DAGLA)抗体相关自身免疫性脑炎。方法：通过单次静脉输注针对CD19和消耗B细胞的全人第二代CAR - T细胞（KYV-101）进行治疗。临床反应采用国际合作共济失调评定量表和自身免疫性脑炎临床评定量表进行评分。采用基于重组细胞的间接免疫荧光法检测血清和脑脊液中抗DAGLA的自身抗体，并通过小鼠原代神经元和脑切片染色证实。结果：一名36岁男性，尽管接受了脉冲糖皮质激素治疗、血浆置换和利妥昔单抗治疗，但仍迅速发展为全身性肌阵挛、小脑性头震颤、垂直双目眼球震颤和四肢瘫。抗dagla抗体在间接免疫荧光试验、血清和脑脊液中呈阳性，并与神经元和脑切片反应。由于患者临床病情严重，治疗难治性，患者接受了单次自体抗cd19 CAR - T细胞输注。治疗后临床评分明显提高，血清和脑脊液抗dagla抗体水平降低。脑脊液中的寡克隆带最初呈阳性，经CAR - T细胞治疗后变为阴性。结论：该报告强调了抗cd19 CAR - T细胞治疗严重难治性自身免疫性脑炎的治疗潜力。经费：没有外部资金用于治疗或产生的数据。

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来源期刊

Med MEDICINE, RESEARCH & EXPERIMENTAL-

CiteScore

17.70

自引率

0.60%

发文量

102

期刊介绍： Med is a flagship medical journal published monthly by Cell Press, the global publisher of trusted and authoritative science journals including Cell, Cancer Cell, and Cell Reports Medicine. Our mission is to advance clinical research and practice by providing a communication forum for the publication of clinical trial results, innovative observations from longitudinal cohorts, and pioneering discoveries about disease mechanisms. The journal also encourages thought-leadership discussions among biomedical researchers, physicians, and other health scientists and stakeholders. Our goal is to improve health worldwide sustainably and ethically. Med publishes rigorously vetted original research and cutting-edge review and perspective articles on critical health issues globally and regionally. Our research section covers clinical case reports, first-in-human studies, large-scale clinical trials, population-based studies, as well as translational research work with the potential to change the course of medical research and improve clinical practice.