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The first clinical applications of CAR T-cell therapy for autoimmune diseases have demonstrated promising efficacy, particularly in systemic lupus erythematosus and myasthenia gravis. While CAR T-cell therapy can induce profound B-cell depletion, leading to durable remission, concerns remain regarding cytokine release syndrome and immune effector cell-associated neurotoxicity syndrome. However, neuroimmunological conditions with lower target cell burdens may carry a reduced risk of these adverse events. Recent evidence suggests CAR T-cells could offer a transformative approach for stiff-person syndrome (SPS), a rare but debilitating autoimmune neurological disorder characterized by muscle rigidity and spasms. The first reported case of anti-CD19 CAR T-cell therapy in a treatment-refractory SPS patient resulted in substantial clinical improvement, including increased mobility and reduced dependence on symptomatic medication. A newly launched phase II clinical trial (NCT06588491) aims to further evaluate the safety and efficacy of anti-CD19 CAR T-cell therapy in SPS. In this review, we examine the current evidence supporting the use of CAR T-cells in neuroimmunological conditions, discuss the clinical picture and pathophysiological processes associated with stiff person spectrum disorders (SPSD), and elaborate on perspectives and limitations of CAR T-cell therapy in SPSD and beyond.<\/jats:p>","DOI":"10.1177\/17562864251387930","type":"journal-article","created":{"date-parts":[[2025,11,10]],"date-time":"2025-11-10T09:29:06Z","timestamp":1762766946000},"update-policy":"https:\/\/doi.org\/10.1177\/sage-journals-update-policy","source":"Crossref","is-referenced-by-count":3,"title":["Chimeric antigen receptor T-cell therapy for stiff-person syndrome: bridging innovation and clinical challenges in neuroimmunology"],"prefix":"10.1177","volume":"18","author":[{"given":"Jonathan","family":"Wickel","sequence":"first","affiliation":[{"name":"Section Translational Neuroimmunology, Department of Neurology, Jena University Hospital, Jena, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6624-8565","authenticated-orcid":false,"given":"Jeremias","family":"Motte","sequence":"additional","affiliation":[{"name":"Department of Neurology, Ruhr-University Bochum, St. Josef-Hospital, Bochum, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ilya","family":"Ayzenberg","sequence":"additional","affiliation":[{"name":"Department of Neurology, Ruhr-University Bochum, St. Josef-Hospital, Bochum, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Benjamin","family":"Vlad","sequence":"additional","affiliation":[{"name":"Section Translational Neuroimmunology, Department of Neurology, Jena University Hospital, Jena, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7223-3052","authenticated-orcid":false,"given":"Ralf","family":"Gold","sequence":"additional","affiliation":[{"name":"Department of Neurology, Ruhr-University Bochum, St. Josef-Hospital, Bochum, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Christian","family":"Geis","sequence":"additional","affiliation":[{"name":"Section Translational Neuroimmunology, Department of Neurology, Jena University, Am Klinikum 1, Jena 07747, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3412-762X","authenticated-orcid":false,"given":"Simon","family":"Faissner","sequence":"additional","affiliation":[{"name":"Department of Neurology, Ruhr-University Bochum, St. Josef-Hospital, Gudrunstr. 56, Bochum 44791, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"179","published-online":{"date-parts":[[2025,11,10]]},"reference":[{"key":"e_1_3_4_2_2","doi-asserted-by":"publisher","DOI":"10.1016\/S1474-4422(24)00140-6"},{"key":"e_1_3_4_3_2","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa1215134"},{"key":"e_1_3_4_4_2","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa1804980"},{"key":"e_1_3_4_5_2","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa1709866"},{"key":"e_1_3_4_6_2","doi-asserted-by":"publisher","DOI":"10.1200\/JCO.22.02345"},{"key":"e_1_3_4_7_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.jcyt.2024.09.008"},{"key":"e_1_3_4_8_2","doi-asserted-by":"publisher","DOI":"10.1182\/bloodadvances.2024013586"},{"key":"e_1_3_4_9_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-024-54150-z"},{"key":"e_1_3_4_10_2","doi-asserted-by":"publisher","DOI":"10.1158\/2159-8290.CD-17-0698"},{"issue":"20","key":"e_1_3_4_11_2","first-page":"2430","article-title":"How I treat refractory CRS and ICANS after CAR T-cell therapy","volume":"141","author":"Jain MD","year":"2023","unstructured":"Jain MD, Smith M, Shah NN. 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