Single-cell analysis of anti-BCMA CAR T cell therapy in patients with central nervous system autoimmunity
Chuan Qin, Min Zhang, Dapeng Mou, Luo‐Qi Zhou, Ming‐Hao Dong, Liang Huang, Wen Wang, Wen Wang, Song-Bai Cai, Yun‐Fan You, Ke Shang, Jun Xiao, Di Wang, Chunrui Li, Yi Hao, Michael Heming, Long‐Jun Wu, Gerd Meyer zu Hörste, Chen Dong, Bi-Tao Bu, Dai‐Shi Tian, Wei Wang, Wei Wang
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.