{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,29]],"date-time":"2026-09-29T06:04:08Z","timestamp":1790661848302,"version":"4.1.0"},"reference-count":16,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,9,29]],"date-time":"2026-09-29T00:00:00Z","timestamp":1790640000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Immunol."],"abstract":"<jats:p>Refractory secondary progressive multiple sclerosis (SPMS) remains an area of unmet need, particularly once disability continues to accumulate despite multiple disease-modifying therapies. Two SPMS patients are reported with C-CAR168 treatment, a bispecific CD20\/BCMA CAR-T product, achieving 12- and 6-month drug-free remission. Patient 001 (EDSS 4.0\u21923.0) showed improvement of oculomotor dysfunction, ataxia, and cognitive impairment. Patient 002 (EDSS 6.5\u21926.0) demonstrated halted lower-limb progression and relieved bowel\/bladder dysfunction. C-CAR168 infiltrated into the cerebrospinal fluid (CSF), persistently depleted pathogenic B-lineage cells and CD20dim T cells, and normalized inflammatory markers with an overall favorable safety profile. This first-in-human experience supports bispecific CAR-T as a promising immune-reprogramming strategy for refractory SPMS.<\/jats:p>","DOI":"10.3389\/fimmu.2026.1965459","type":"journal-article","created":{"date-parts":[[2026,9,29]],"date-time":"2026-09-29T05:48:34Z","timestamp":1790660914000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":0,"title":["Case Report: CD20\/BCMA bispecific CAR-T therapy for progressive multiple sclerosis"],"prefix":"10.3389","volume":"17","author":[{"given":"Zhenfen","family":"Ling","sequence":"first","affiliation":[{"name":"Shanghai General Hospital","place":["Shanghai, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xia","family":"Liu","sequence":"additional","affiliation":[{"name":"Shanghai General Hospital","place":["Shanghai, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wensi","family":"Li","sequence":"additional","affiliation":[{"name":"Shanghai AbelZeta Ltd.","place":["Shanghai, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Qingguo","family":"Wang","sequence":"additional","affiliation":[{"name":"Shanghai General Hospital","place":["Shanghai, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nu","family":"Tan","sequence":"additional","affiliation":[{"name":"Shanghai General Hospital","place":["Shanghai, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xueying","family":"Ding","sequence":"additional","affiliation":[{"name":"Shanghai General Hospital","place":["Shanghai, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yunyi","family":"Zan","sequence":"additional","affiliation":[{"name":"Shanghai General Hospital","place":["Shanghai, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Youyao","family":"Gu","sequence":"additional","affiliation":[{"name":"Shanghai AbelZeta Ltd.","place":["Shanghai, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yuan","family":"Qian","sequence":"additional","affiliation":[{"name":"Shanghai AbelZeta Ltd.","place":["Shanghai, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiaobing","family":"Luo","sequence":"additional","affiliation":[{"name":"AbelZeta Inc.","place":["Rockville, MD, United States"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Thule","family":"Trinh","sequence":"additional","affiliation":[{"name":"AbelZeta Inc.","place":["Rockville, MD, United States"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yanfeng","family":"Li","sequence":"additional","affiliation":[{"name":"Shanghai AbelZeta Ltd.","place":["Shanghai, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiaoteng","family":"Lv","sequence":"additional","affiliation":[{"name":"Shanghai AbelZeta Ltd.","place":["Shanghai, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Minna","family":"Wang","sequence":"additional","affiliation":[{"name":"Shanghai AbelZeta Ltd.","place":["Shanghai, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Qian","family":"Tan","sequence":"additional","affiliation":[{"name":"Shanghai AbelZeta Ltd.","place":["Shanghai, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kevin","family":"Zhu","sequence":"additional","affiliation":[{"name":"The University of Vermont Medical Center","place":["Burlington, VT, United States"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chengxiao","family":"Zheng","sequence":"additional","affiliation":[{"name":"Shanghai AbelZeta Ltd.","place":["Shanghai, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xin","family":"Yao","sequence":"additional","affiliation":[{"name":"AbelZeta Inc.","place":["Rockville, MD, United States"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Judy","family":"Zhu","sequence":"additional","affiliation":[{"name":"Shanghai AbelZeta Ltd.","place":["Shanghai, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jiaqi","family":"Huang","sequence":"additional","affiliation":[{"name":"AbelZeta Inc.","place":["Rockville, MD, United States"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yihong","family":"Yao","sequence":"additional","affiliation":[{"name":"AbelZeta Inc.","place":["Rockville, MD, United States"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nan","family":"Shen","sequence":"additional","affiliation":[{"name":"Renji Hospital, Shanghai Jiao Tong University School of Medicine","place":["Shanghai, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2026,9,29]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(18)30481-1","article-title":"Multiple sclerosis","volume":"391","author":"Thompson","year":"2018","journal-title":"Lancet"},{"key":"B2","doi-asserted-by":"publisher","first-page":"183","DOI":"10.1016\/S0140-6736(23)01473-3","article-title":"Multiple sclerosis","volume":"403","author":"Jakimovski","year":"2024","journal-title":"Lancet"},{"key":"B3","doi-asserted-by":"publisher","first-page":"95","DOI":"10.1016\/S1474-4422(23)00377-0","article-title":"Blood-brain barrier dysfunction in multiple sclerosis: causes, consequences, and potential effects of therapies","volume":"23","author":"Zierfuss","year":"2024","journal-title":"Lancet Neurol"},{"key":"B4","doi-asserted-by":"publisher","DOI":"10.1186\/2047-783X-19-20","article-title":"Multiple sclerosis: clinical features and MRI findings in Northern China","volume":"19","author":"Li","year":"2014","journal-title":"Eur J Med Res"},{"key":"B5","doi-asserted-by":"publisher","DOI":"10.1016\/j.jns.2007.09.010","article-title":"Heterogeneity and continuum of multiple sclerosis in Japanese according to magnetic resonance imaging findings","volume":"266","author":"Matsuoka","year":"2008","journal-title":"J Neurol Sci"},{"key":"B6","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0098192","article-title":"Poor responses to interferon-beta treatment in patients with neuromyelitis optica and multiple sclerosis with long spinal cord lesions","volume":"9","author":"Wang","year":"2014","journal-title":"PloS One"},{"key":"B7","doi-asserted-by":"publisher","first-page":"550","DOI":"10.1016\/j.medj.2024.03.002","article-title":"CD19-targeted chimeric antigen receptor T cell therapy in two patients with multiple sclerosis","volume":"5","author":"Fischbach","year":"2024","journal-title":"Med"},{"key":"B8","doi-asserted-by":"publisher","first-page":"6414","DOI":"10.1016\/j.cell.2025.09.020","article-title":"Anti-BCMA CAR T-cell therapy in patients with multiple sclerosis","volume":"188","author":"Qin","year":"2025","journal-title":"Cell"},{"key":"B9","article-title":"Anti-CD20\/BCMA bispecific CAR-T cell therapy promotes immune reset and sustained drug free remission in refractory autoimmune diseases [abstract","volume":"77","author":"Ding","year":"2025","journal-title":"Arthritis Rheumatol"},{"key":"B10","doi-asserted-by":"publisher","DOI":"10.1016\/S1474-4422(17)30470-2","article-title":"Diagnosis of multiple sclerosis: 2017 revisions of the McDonald criteria","volume":"17","author":"Thompson","year":"2018","journal-title":"Lancet Neurol"},{"key":"B11","doi-asserted-by":"publisher","DOI":"10.1146\/annurev-pathol-052920-040318","article-title":"The immune response in multiple sclerosis","volume":"17","author":"Mur\u00faa","year":"2022","journal-title":"Annu Rev Pathol"},{"key":"B12","doi-asserted-by":"publisher","DOI":"10.3390\/ijms26146655","article-title":"CD20+ T cells in multiple sclerosis: from pathogenesis to treatment-induced depletion","volume":"26","author":"Mazzeo","year":"2025","journal-title":"Int J Mol Sci"},{"key":"B13","doi-asserted-by":"publisher","first-page":"13","DOI":"10.1002\/ana.25927","article-title":"Role of B cells in multiple sclerosis and related disorders","volume":"89","author":"Comi","year":"2021","journal-title":"Ann Neurol"},{"key":"B14","doi-asserted-by":"publisher","DOI":"10.1007\/s00415-023-12081-7","article-title":"The elusive nature of the oligoclonal bands in multiple sclerosis","volume":"271","author":"Kennedy","year":"2024","journal-title":"J Neurol"},{"key":"B15","doi-asserted-by":"publisher","DOI":"10.3389\/fneur.2026.1815022","article-title":"Serum neurofilament light chain in multiple sclerosis: from biological signal to clinically informed decision-making","volume":"17","author":"Caminero","year":"2026","journal-title":"Front Neurol"},{"key":"B16","doi-asserted-by":"publisher","DOI":"10.1212\/WNL.0000000000000560","article-title":"Defining the clinical course of multiple sclerosis: the 2013 revisions","volume":"83","author":"Lublin","year":"2014","journal-title":"Neurology"}],"container-title":["Frontiers in Immunology"],"original-title":[],"link":[{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fimmu.2026.1965459\/full","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,9,29]],"date-time":"2026-09-29T05:48:35Z","timestamp":1790660915000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fimmu.2026.1965459\/full"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,9,29]]},"references-count":16,"alternative-id":["10.3389\/fimmu.2026.1965459"],"URL":"https:\/\/doi.org\/10.3389\/fimmu.2026.1965459","relation":{},"ISSN":["1664-3224"],"issn-type":[{"value":"1664-3224","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,9,29]]},"article-number":"1965459"}}