TY  - JOUR
AU  - Konitsioti, Agni M.
AU  - Prüss, Harald
AU  - Laurent, Sarah
AU  - Fink, Gereon Rudolf
AU  - Heesen, Christoph
AU  - Warnke, Clemens
TI  - Chimeric antigen receptor T-cell therapy for autoimmune diseases of the central nervous system: a systematic literature review
JO  - Journal of neurology
VL  - 271
IS  - 10
SN  - 0367-004X
CY  - [Darmstadt]
PB  - Steinkopff
M1  - FZJ-2025-00573
SP  - 6526 - 6542
PY  - 2024
N1  - Funding Open Access funding enabled and organized by Projekt DEAL.
AB  - Importance: B-cell-targeting monoclonal antibodies have demonstrated safety and efficacy in multiple sclerosis or anti-aquaporin-4 IgG positive neuromyelitis optica spectrum disorder. However, these therapies do not facilitate drug-free remission, which may become possible with cell-based therapies, including chimeric antigen receptor (CAR) T cells. CAR T-cell therapy holds promise for addressing other antibody-mediated CNS disorders, e.g., MOG-associated disease or autoimmune encephalitis.Objective: To provide an overview of the current clinical knowledge on CAR T-cell therapy in central nervous system autoimmunity.Evidence review: We searched PubMed, Embase, Google Scholar, PsycINFO, and clinicaltrials.gov using the terms 'CAR T cell' and 'multiple sclerosis/MS' or 'neuromyelitis optica/spectrum diseases/NMOSD' or 'MOG-associated disease/MOGAD 'or' autoimmune encephalitis' or 'neuroimmunology'.Findings: An ongoing phase I clinical trial has indicated the safety and benefits of anti-BCMA CAR T cells in 12 patients with AQP4-IgG seropositive neuromyelitis optica spectrum disorder. Case reports involving two individuals with progressive multiple sclerosis and one patient with stiff-person syndrome demonstrated a manageable safety profile following treatment with anti-CD19 CAR T cells. Recruitment has commenced for two larger studies in MS, and a phase I open-label basket study is underway to evaluate BCMA-directed CAR T cells in various antibody-associated inflammatory diseases, including MOG-associated disease. Preclinical research on NMDA receptor antibody autoimmune encephalitis treated with chimeric autoantibody receptor T cells generated promising data.Conclusions and relevance: There is minimal evidence of the benefits of CAR T-cell therapy in individuals with central nervous system-directed autoimmunity. Nevertheless, multicenter controlled clinical trials with a manageable safety profile appear feasible and are warranted due to very promising case experiences.Keywords: Antibody-mediated CNS disorders; CAR T-cell therapy; Central nervous system autoimmunity; Multiple sclerosis; NMOSD.
LB  - PUB:(DE-HGF)16
C6  - 39276207
UR  - <Go to ISI:>//WOS:001321346700002
DO  - DOI:10.1007/s00415-024-12642-4
UR  - https://juser.fz-juelich.de/record/1037240
ER  -