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Single-cell analysis of anti-BCMA CAR T cell therapy in patients with central nervous system autoimmunity

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单位： [1]Department of Neurology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, China. [2]Hubei Key Laboratory of Neural Injury and Functional Reconstruction, Huazhong University of Science and Technology, Wuhan 430030, China. [3]Beijing Tongren Eye Center, Beijing Tongren Hospital, Capital Medical University, Beijing Ophthalmology & Visual Science Key Lab, Beijing, China. [4]Department of Hematology, Tongji Hospital of Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China [5]Nanjing IASO Biotechnology Co. Ltd., Nanjing, China. [6]Department of Pathogen Biology, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, China. [7]Department of Neurology with Institute of Translational Neurology, University Hospital Münster, Münster, Germany. [8]Department of Neurology, Mayo Clinic, Rochester, MN 55905, USA. [9]Shanghai Immune Therapy Institute, Shanghai Jiaotong University School of Medicine–affiliated Renji Hospital, Shanghai, China.

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摘要：

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.

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出版当年[2023]版：

大类 | 1 区

医学

小类 | 1 区免疫学

最新[2025]版：

大类 | 1 区

医学

小类 | 1 区免疫学

第一作者：

第一作者单位： [1]Department of Neurology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, China. [2]Hubei Key Laboratory of Neural Injury and Functional Reconstruction, Huazhong University of Science and Technology, Wuhan 430030, China.

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通讯作者：

通讯机构： [1]Department of Neurology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, China. [2]Hubei Key Laboratory of Neural Injury and Functional Reconstruction, Huazhong University of Science and Technology, Wuhan 430030, China.

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