{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"institution":[{"name":"medRxiv"}],"indexed":{"date-parts":[[2026,9,15]],"date-time":"2026-09-15T12:04:40Z","timestamp":1789473880853,"version":"build-2803163510"},"posted":{"date-parts":[[2026,9,11]]},"group-title":"Neurology","reference-count":79,"publisher":"openRxiv","license":[{"start":{"date-parts":[[2026,9,11]],"date-time":"2026-09-11T00:00:00Z","timestamp":1789084800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/www.medrxiv.org\/about\/FAQ#license"}],"funder":[{"award":["MU 5558\/1-1"],"award-info":[{"award-number":["MU 5558\/1-1"]}],"id":[{"id":"https:\/\/ror.org\/044wq1q96","id-type":"ROR","asserted-by":"publisher"}]},{"name":"University of British Columbia Clinician Investigator Program"},{"award":["K23NS140543"],"award-info":[{"award-number":["K23NS140543"]}],"id":[{"id":"https:\/\/ror.org\/001d55x84","id-type":"ROR","asserted-by":"publisher"}]},{"award":["TA-2404-43033"],"award-info":[{"award-number":["TA-2404-43033"]}],"id":[{"id":"https:\/\/ror.org\/03019wv17","id-type":"ROR","asserted-by":"publisher"}]},{"name":"Kyverna Therapeutics"},{"name":"Tim and Laura O\u2019Shaughnessy, the Littera Family, and the Westridge, Valhalla, and Spangler Foundations"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"accepted":{"date-parts":[[2026,9,11]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                <jats:p>Treatment targeting progressive multiple sclerosis (MS) have limited efficacy, as central nervous system (CNS) resident B cells are resistant to peripheral B cell depletion by anti-CD20 monoclonal antibodies. CD19-targeted chimeric antigen receptor (CAR)-T cells offer the promise to deplete B cells more extensively in both the peripheral and CNS compartments. Two adult participants with treatment-refractory progressive MS were treated with 0.33\u00d710^8 autologous anti-CD19 CAR-T cells (mivocabtagene autoleucel, miv-cel) intravenously after a preconditioning regimen. Participant 1 (50\u2019s year old female, EDSS 6) had no cytokine release syndrome (CRS) or immune effector cell-associated neurotoxicity syndrome (ICANS). Participant 2 (60\u2019s year old female, EDSS 4.5) had grade 1 CRS and no ICANS. Expansion of CAR-T cells in the cerebrospinal fluid (CSF) at Day 14 was noted in both participants, remarkably with sustained disappearance of disease-associated oligoclonal band (OCB) or normalization of IgG index despite peripheral naive B cell reconstitution. MRI and clinical outcomes showed sustained stability at Week 48. Serologic studies showed a decline in anti-Epstein Barr Virus seropositivity. Single cell myeloid and proteomic signatures showed a decline in proinflammatory profiles.<\/jats:p>\n                <jats:p>In the 2 subjects with progressive MS reported here, low dose anti-CD19 CAR-T cell therapy (miv-cel) was safe, penetrated the CSF effectively, reduced intrathecal humoral activity, modulated peripheral immune tone, and appeared to stabilize EDSS scores. Overall, these results support the continued investigation of CAR-T cell therapy in MS.<\/jats:p>\n                <jats:sec>\n                  <jats:title>One Sentence Summary<\/jats:title>\n                  <jats:p>Anti-CD19 CAR-T cell was safe in two progressive MS patients with CSF penetration, OCB\/IgG index resolution, and improved inflammatory background.<\/jats:p>\n                <\/jats:sec>","DOI":"10.64898\/2026.09.11.26361992","type":"posted-content","created":{"date-parts":[[2026,9,12]],"date-time":"2026-09-12T03:55:12Z","timestamp":1789185312000},"source":"Crossref","is-referenced-by-count":0,"title":["Immune Profiling after treatment with an Anti-CD19 Chimeric Antigen Receptor T Cell Therapy in Treatment-Refractory Progressive Multiple Sclerosis"],"prefix":"10.64898","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-1972-7301","authenticated-orcid":false,"given":"Sasha","family":"Gupta","sequence":"first","affiliation":[{"name":"Weill Institute for Neurosciences, 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