CD19xCD3 T-cell engager blinatumomab effective in refractory generalized myasthenic syndromes

IF 12.1 1区 医学 Q1 BIOTECHNOLOGY & APPLIED MICROBIOLOGY
Tobias Ruck M.D., Niklas Huntemann M.D., Menekse Öztürk M.D., Stefanie Schreiber M.D., Stefanie Lichtenberg Ph.D., Lars Masanneck M.D., Christopher Nelke M.D., Hend Ben Moussa M.D., Thomas Ulrych M.D., Marc Seifert Ph.D., Dimitrios Mougiakakos M.D., Sascha Dietrich M.D., Sven G. Meuth M.D. Ph.D.
{"title":"CD19xCD3 T-cell engager blinatumomab effective in refractory generalized myasthenic syndromes","authors":"Tobias Ruck M.D., Niklas Huntemann M.D., Menekse Öztürk M.D., Stefanie Schreiber M.D., Stefanie Lichtenberg Ph.D., Lars Masanneck M.D., Christopher Nelke M.D., Hend Ben Moussa M.D., Thomas Ulrych M.D., Marc Seifert Ph.D., Dimitrios Mougiakakos M.D., Sascha Dietrich M.D., Sven G. Meuth M.D. Ph.D.","doi":"10.1016/j.ymthe.2025.06.042","DOIUrl":null,"url":null,"abstract":"In this case series, we report the first off-label use of the CD19xCD3 T-cell engager blinatumomab in two patients with generalized myasthenia gravis (MG). Refractory MG remains a major therapeutic challenge, with patients experiencing severe disability and potentially life-threatening crises despite intensive immunotherapy. This study evaluates the clinical efficacy and safety of short-term blinatumomab treatment in two patients with severe, refractory generalized MG. Both individuals had been experiencing a persistent disease burden with myasthenic crises leading to severe disability, despite multimodal immunotherapy. Following treatment with blinatumomab, both patients showed rapid and sustained clinical improvements, reflected in significant reductions in MG-specific scores (MG-ADL, QMG, and revised MG Quality of Life-15), further patient-reported outcomes, digital activity markers, and gait analyses. Laboratory findings revealed persistent B-cell depletion in patient #1, whereas patient #2 demonstrated clinical improvement and autoantibody reduction despite B-cell repopulation by day 106. Both patients experienced grade 1 cytokine release syndrome during initial treatment phases, but no neurotoxicity or severe adverse events were observed. This report underscores the potential of CD19xCD3 T-cell engagers as a promising therapeutic approach in severe autoimmune neuroimmunological disorders, warranting further investigation in clinical trials and mechanistic studies.","PeriodicalId":19020,"journal":{"name":"Molecular Therapy","volume":"24 1","pages":""},"PeriodicalIF":12.1000,"publicationDate":"2025-06-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"Molecular Therapy","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.1016/j.ymthe.2025.06.042","RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q1","JCRName":"BIOTECHNOLOGY & APPLIED MICROBIOLOGY","Score":null,"Total":0}
引用次数: 0

Abstract

In this case series, we report the first off-label use of the CD19xCD3 T-cell engager blinatumomab in two patients with generalized myasthenia gravis (MG). Refractory MG remains a major therapeutic challenge, with patients experiencing severe disability and potentially life-threatening crises despite intensive immunotherapy. This study evaluates the clinical efficacy and safety of short-term blinatumomab treatment in two patients with severe, refractory generalized MG. Both individuals had been experiencing a persistent disease burden with myasthenic crises leading to severe disability, despite multimodal immunotherapy. Following treatment with blinatumomab, both patients showed rapid and sustained clinical improvements, reflected in significant reductions in MG-specific scores (MG-ADL, QMG, and revised MG Quality of Life-15), further patient-reported outcomes, digital activity markers, and gait analyses. Laboratory findings revealed persistent B-cell depletion in patient #1, whereas patient #2 demonstrated clinical improvement and autoantibody reduction despite B-cell repopulation by day 106. Both patients experienced grade 1 cytokine release syndrome during initial treatment phases, but no neurotoxicity or severe adverse events were observed. This report underscores the potential of CD19xCD3 T-cell engagers as a promising therapeutic approach in severe autoimmune neuroimmunological disorders, warranting further investigation in clinical trials and mechanistic studies.
CD19xCD3 t细胞参与blinatumumab对难治性全身性肌无力综合征有效
在本病例系列中,我们报道了CD19xCD3 t细胞参与者blinatumumab在两例全身性重症肌无力(MG)患者中的首次非适应症使用。难治性MG仍然是一个主要的治疗挑战,尽管进行了强化免疫治疗,患者仍会出现严重的残疾和潜在的危及生命的危机。本研究评估了布利纳单抗短期治疗2例严重难治性全身性MG患者的临床疗效和安全性。尽管进行了多模式免疫治疗,但两个人都经历了持续的疾病负担,并伴有肌无力危机,导致严重残疾。在使用blinatumomab治疗后,两名患者均表现出快速和持续的临床改善,反映在MG特异性评分(MG- adl, QMG和修订MG生活质量15)的显着降低,进一步的患者报告结果,数字活动标记和步态分析。实验室结果显示患者1持续的b细胞耗竭,而患者2表现出临床改善和自身抗体减少,尽管b细胞在第106天重新聚集。两名患者在初始治疗阶段均出现1级细胞因子释放综合征,但未观察到神经毒性或严重不良事件。该报告强调了CD19xCD3 t细胞结合物作为严重自身免疫性神经免疫疾病的一种有希望的治疗方法的潜力,值得在临床试验和机制研究中进一步研究。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
求助全文
约1分钟内获得全文 求助全文
来源期刊
Molecular Therapy
Molecular Therapy 医学-生物工程与应用微生物
CiteScore
19.20
自引率
3.20%
发文量
357
审稿时长
3 months
期刊介绍: Molecular Therapy is the leading journal for research in gene transfer, vector development, stem cell manipulation, and therapeutic interventions. It covers a broad spectrum of topics including genetic and acquired disease correction, vaccine development, pre-clinical validation, safety/efficacy studies, and clinical trials. With a focus on advancing genetics, medicine, and biotechnology, Molecular Therapy publishes peer-reviewed research, reviews, and commentaries to showcase the latest advancements in the field. With an impressive impact factor of 12.4 in 2022, it continues to attract top-tier contributions.
×
引用
GB/T 7714-2015
复制
MLA
复制
APA
复制
导出至
BibTeX EndNote RefMan NoteFirst NoteExpress
×
提示
您的信息不完整,为了账户安全,请先补充。
现在去补充
×
提示
您因"违规操作"
具体请查看互助需知
我知道了
×
提示
确定
请完成安全验证×
copy
已复制链接
快去分享给好友吧!
我知道了
右上角分享
点击右上角分享
0
联系我们:info@booksci.cn Book学术提供免费学术资源搜索服务,方便国内外学者检索中英文文献。致力于提供最便捷和优质的服务体验。 Copyright © 2023 布克学术 All rights reserved.
京ICP备2023020795号-1
ghs 京公网安备 11010802042870号
Book学术文献互助
Book学术文献互助群
群 号:604180095
Book学术官方微信