Konitsioti AM, Prüss H, Lauren S, Fink GR, Heesen C, Warnke C.
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.
J Neurol. 2024 Sep 14.
Link to Pubmed