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- Title
Single-cell analysis of anti-BCMA CAR T cell therapy in patients with central nervous system autoimmunity.
- Authors
Qin, Chuan; Zhang, Min; Mou, Da-Peng; Zhou, Luo-Qi; Dong, Ming-Hao; Huang, Liang; Wang, Wen; Cai, Song-Bai; You, Yun-Fan; Shang, Ke; Xiao, Jun; Wang, Di; Li, Chun-Rui; Hao, Yi; Heming, Michael; Wu, Long-Jun; Hörste, Gerd Meyer Zu; Dong, Chen; Bu, Bi-Tao; Tian, Dai-Shi
- 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. Editor's summary: Chimeric antigen receptor (CAR) T cell therapy is a promising avenue for the treatment of autoimmunity, but how these cells work in vivo is poorly understood. Qin et al. performed a single-cell multi-omics analysis of longitudinal blood and cerebrospinal fluid (CSF) samples from five patients with neuromyelitis optica spectrum disease (NMOSD) undergoing treatment with anti–B cell maturation antigen (BCMA) CAR T cells. They characterized CAR T cell expansion and function and found that peak expansion occurred within 10 days. Moreover, persistent CSF-infiltrating CAR T clones were CXCR3+ and exhibited an enhanced chemotactic transcriptional program. Last, Qin et al. observed that CAR T cells taken from treated patients with NMOSD were less cytotoxic than CAR T cells taken from treated patients with myeloma and patients with B cell lymphoma. These findings may help optimize future immunotherapies for autoimmune disorders. —Seth Thomas Scanlon
- Subjects
CHIMERIC antigen receptors; CENTRAL nervous system; NEUROMYELITIS optica; B cell lymphoma; T cells
- Publication
Science Immunology, 2024, Vol 9, Issue 95, p1
- ISSN
2470-9468
- Publication type
Article
- DOI
10.1126/sciimmunol.adj9730