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

Sci Immunol. 2024 May 10;9(95):eadj9730. doi: 10.1126/sciimmunol.adj9730. Epub 2024 May 10.


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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Autoimmunity* / immunology
  • Central Nervous System / immunology
  • Female
  • Humans
  • Immunotherapy, Adoptive*
  • Male
  • Middle Aged
  • Neuromyelitis Optica / immunology
  • Neuromyelitis Optica / therapy
  • Receptors, Chimeric Antigen* / immunology
  • Single-Cell Analysis


  • Receptors, Chimeric Antigen