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
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引用次数: 0
Abstract
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.
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。
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.