Single-cell analysis of anti-BCMA CAR T cell therapy in patients with central nervous system autoimmunity.
Sci Immunol
; 9(95): eadj9730, 2024 05 10.
Article
em En
| MEDLINE
| ID: mdl-38728414
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.
Texto completo:
1
Base de dados:
MEDLINE
Assunto principal:
Autoimunidade
/
Imunoterapia Adotiva
/
Receptores de Antígenos Quiméricos
Idioma:
En
Ano de publicação:
2024
Tipo de documento:
Article