Chimeric antigen receptor T-cell therapy for autoimmune diseases of the central nervous system: a systematic literature review

TY - JOUR

T1 - Chimeric antigen receptor T-cell therapy for autoimmune diseases of the central nervous system: a systematic literature review

AU - Konitsioti, Agni M

AU - Prüss, Harald

AU - Laurent, Sarah

AU - Fink, Gereon R

AU - Heesen, Christoph

AU - Warnke, Clemens

N1 - © 2024. The Author(s).

PY - 2024/10

Y1 - 2024/10

N2 - 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.

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.

U2 - 10.1007/s00415-024-12642-4

DO - 10.1007/s00415-024-12642-4

M3 - SCORING: Review article

C2 - 39276207

VL - 271

SP - 6526

EP - 6542

JO - J NEUROL

JF - J NEUROL

SN - 0340-5354

IS - 10

ER -