Citations 1
Single-cell analysis of anti-BCMA CAR T cell therapy in patients with central nervous system autoimmunity
Qin, Chuan , Zhang, Min , Mou, Dapeng , Zhou, Luo‐Qi , Dong, Ming‐Hao , Huang, Liang , Wang, Wen , Cai, Song-Bai , You, Yun‐Fan , Shang, Ke , Xiao, Jun , Wang, Di , Li, Chunrui , Hao, Yi , Wu, Long‐Jun , Bu, Bi-Tao, Wang, Wei , Li, Chun-Rui , Heming, Michael , Wu, Long-Jun , Meyer Zu Hörste, Gerd , Dong, Chen , Bu, Bi-Tao , Tian, Dai-Shi , Wang, Wei , Wang, Wen , Tian, Dai‐Shi
Science Immunology | May 10, 2024 | Volume: 9 | Issue: 95 | Pages: No page available
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.