对中枢神经系统自身免疫患者进行抗 BCMA CAR T 细胞疗法的单细胞分析。

IF 17.6 1区 医学 Q1 IMMUNOLOGY
Chuan Qin, Min Zhang, Da-Peng Mou, Luo-Qi Zhou, Ming-Hao Dong, Liang Huang, Wen Wang, Song-Bai Cai, Yun-Fan You, Ke Shang, Jun Xiao, Di Wang, Chun-Rui Li, Yi Hao, Michael Heming, Long-Jun Wu, Gerd Meyer Zu Hörste, Chen Dong, Bi-Tao Bu, Dai-Shi Tian, Wei Wang
{"title":"对中枢神经系统自身免疫患者进行抗 BCMA CAR T 细胞疗法的单细胞分析。","authors":"Chuan Qin,&nbsp;Min Zhang,&nbsp;Da-Peng Mou,&nbsp;Luo-Qi Zhou,&nbsp;Ming-Hao Dong,&nbsp;Liang Huang,&nbsp;Wen Wang,&nbsp;Song-Bai Cai,&nbsp;Yun-Fan You,&nbsp;Ke Shang,&nbsp;Jun Xiao,&nbsp;Di Wang,&nbsp;Chun-Rui Li,&nbsp;Yi Hao,&nbsp;Michael Heming,&nbsp;Long-Jun Wu,&nbsp;Gerd Meyer Zu Hörste,&nbsp;Chen Dong,&nbsp;Bi-Tao Bu,&nbsp;Dai-Shi Tian,&nbsp;Wei Wang","doi":"10.1126/sciimmunol.adj9730","DOIUrl":null,"url":null,"abstract":"<div >Chimeric antigen receptor (CAR) T cell immunotherapy for the treatment of neurological autoimmune diseases is promising, but CAR T cell kinetics and immune alterations after treatment are poorly understood. Here, we performed single-cell multi-omics sequencing of paired cerebrospinal fluid (CSF) and blood samples from patients with neuromyelitis optica spectrum disorder (NMOSD) treated with anti–B cell maturation antigen (BCMA) CAR T cells. Proliferating cytotoxic-like CD8<sup>+</sup> CAR T cell clones were identified as the main effectors in autoimmunity. Anti-BCMA CAR T cells with enhanced features of chemotaxis efficiently crossed the blood-CSF barrier, eliminated plasmablasts and plasma cells in the CSF, and suppressed neuroinflammation. The CD44-expressing early memory phenotype in infusion products was potentially associated with CAR T cell persistence in autoimmunity. Moreover, CAR T cells from patients with NMOSD displayed distinctive features of suppressed cytotoxicity compared with those from hematological malignancies. Thus, we provide mechanistic insights into CAR T cell function in patients with neurological autoimmune disease.</div>","PeriodicalId":21734,"journal":{"name":"Science Immunology","volume":"9 95","pages":""},"PeriodicalIF":17.6000,"publicationDate":"2024-05-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.science.org/doi/reader/10.1126/sciimmunol.adj9730","citationCount":"0","resultStr":"{\"title\":\"Single-cell analysis of anti-BCMA CAR T cell therapy in patients with central nervous system autoimmunity\",\"authors\":\"Chuan Qin,&nbsp;Min Zhang,&nbsp;Da-Peng Mou,&nbsp;Luo-Qi Zhou,&nbsp;Ming-Hao Dong,&nbsp;Liang Huang,&nbsp;Wen Wang,&nbsp;Song-Bai Cai,&nbsp;Yun-Fan You,&nbsp;Ke Shang,&nbsp;Jun Xiao,&nbsp;Di Wang,&nbsp;Chun-Rui Li,&nbsp;Yi Hao,&nbsp;Michael Heming,&nbsp;Long-Jun Wu,&nbsp;Gerd Meyer Zu Hörste,&nbsp;Chen Dong,&nbsp;Bi-Tao Bu,&nbsp;Dai-Shi Tian,&nbsp;Wei Wang\",\"doi\":\"10.1126/sciimmunol.adj9730\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<div >Chimeric antigen receptor (CAR) T cell immunotherapy for the treatment of neurological autoimmune diseases is promising, but CAR T cell kinetics and immune alterations after treatment are poorly understood. Here, we performed single-cell multi-omics sequencing of paired cerebrospinal fluid (CSF) and blood samples from patients with neuromyelitis optica spectrum disorder (NMOSD) treated with anti–B cell maturation antigen (BCMA) CAR T cells. Proliferating cytotoxic-like CD8<sup>+</sup> CAR T cell clones were identified as the main effectors in autoimmunity. Anti-BCMA CAR T cells with enhanced features of chemotaxis efficiently crossed the blood-CSF barrier, eliminated plasmablasts and plasma cells in the CSF, and suppressed neuroinflammation. The CD44-expressing early memory phenotype in infusion products was potentially associated with CAR T cell persistence in autoimmunity. Moreover, CAR T cells from patients with NMOSD displayed distinctive features of suppressed cytotoxicity compared with those from hematological malignancies. Thus, we provide mechanistic insights into CAR T cell function in patients with neurological autoimmune disease.</div>\",\"PeriodicalId\":21734,\"journal\":{\"name\":\"Science Immunology\",\"volume\":\"9 95\",\"pages\":\"\"},\"PeriodicalIF\":17.6000,\"publicationDate\":\"2024-05-10\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"https://www.science.org/doi/reader/10.1126/sciimmunol.adj9730\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Science Immunology\",\"FirstCategoryId\":\"3\",\"ListUrlMain\":\"https://www.science.org/doi/10.1126/sciimmunol.adj9730\",\"RegionNum\":1,\"RegionCategory\":\"医学\",\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"\",\"PubModel\":\"\",\"JCR\":\"Q1\",\"JCRName\":\"IMMUNOLOGY\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"Science Immunology","FirstCategoryId":"3","ListUrlMain":"https://www.science.org/doi/10.1126/sciimmunol.adj9730","RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q1","JCRName":"IMMUNOLOGY","Score":null,"Total":0}
引用次数: 0

摘要

用于治疗神经系统自身免疫性疾病的嵌合抗原受体(CAR)T细胞免疫疗法前景广阔,但人们对CAR T细胞动力学和治疗后的免疫改变知之甚少。在这里,我们对接受抗B细胞成熟抗原(BCMA)CAR T细胞治疗的神经脊髓炎视谱系障碍(NMOSD)患者的配对脑脊液(CSF)和血液样本进行了单细胞多组学测序。增殖的细胞毒性类 CD8+ CAR T 细胞克隆被确定为自身免疫的主要效应因子。具有增强趋化特性的抗BCMA CAR T细胞能有效穿过血液-脑脊液屏障,消除脑脊液中的浆细胞和浆细胞,抑制神经炎症。输注产物中表达 CD44 的早期记忆表型可能与 CAR T 细胞在自身免疫中的持久性有关。此外,与来自血液恶性肿瘤的 CAR T 细胞相比,来自 NMOSD 患者的 CAR T 细胞显示出细胞毒性受抑制的独特特征。因此,我们提供了神经系统自身免疫疾病患者 CAR T 细胞功能的机理见解。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
Single-cell analysis of anti-BCMA CAR T cell therapy in patients with central nervous system autoimmunity
Chimeric antigen receptor (CAR) T cell immunotherapy for the treatment of neurological autoimmune diseases is promising, but CAR T cell kinetics and immune alterations after treatment are poorly understood. Here, we performed single-cell multi-omics sequencing of paired cerebrospinal fluid (CSF) and blood samples from patients with neuromyelitis optica spectrum disorder (NMOSD) treated with anti–B cell maturation antigen (BCMA) CAR T cells. Proliferating cytotoxic-like CD8+ CAR T cell clones were identified as the main effectors in autoimmunity. Anti-BCMA CAR T cells with enhanced features of chemotaxis efficiently crossed the blood-CSF barrier, eliminated plasmablasts and plasma cells in the CSF, and suppressed neuroinflammation. The CD44-expressing early memory phenotype in infusion products was potentially associated with CAR T cell persistence in autoimmunity. Moreover, CAR T cells from patients with NMOSD displayed distinctive features of suppressed cytotoxicity compared with those from hematological malignancies. Thus, we provide mechanistic insights into CAR T cell function in patients with neurological autoimmune disease.
求助全文
通过发布文献求助,成功后即可免费获取论文全文。 去求助
来源期刊
Science Immunology
Science Immunology Immunology and Microbiology-Immunology
CiteScore
32.90
自引率
2.00%
发文量
183
期刊介绍: Science Immunology is a peer-reviewed journal that publishes original research articles in the field of immunology. The journal encourages the submission of research findings from all areas of immunology, including studies on innate and adaptive immunity, immune cell development and differentiation, immunogenomics, systems immunology, structural immunology, antigen presentation, immunometabolism, and mucosal immunology. Additionally, the journal covers research on immune contributions to health and disease, such as host defense, inflammation, cancer immunology, autoimmunity, allergy, transplantation, and immunodeficiency. Science Immunology maintains the same high-quality standard as other journals in the Science family and aims to facilitate understanding of the immune system by showcasing innovative advances in immunology research from all organisms and model systems, including humans.
×
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:481959085
Book学术官方微信