{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,11,6]],"date-time":"2026-11-06T06:28:10Z","timestamp":1793946490627,"version":"4.8.0"},"reference-count":32,"publisher":"American Society for Clinical Investigation","issue":"22","funder":[{"name":"MS Queensland, MS Research Australia, Perpetual Trustee Company Ltd, and private donations","award":["Not applicable"],"award-info":[{"award-number":["Not applicable"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2018,11,15]]},"abstract":"<jats:p>\n                    <jats:bold>BACKGROUND.<\/jats:bold>\n                    Increasing evidence indicates a role for EBV in the pathogenesis of multiple sclerosis (MS). EBV-infected autoreactive B cells might accumulate in the CNS because of defective cytotoxic CD8\n                    <jats:sup>+<\/jats:sup>\n                    T cell immunity. We sought to determine the feasibility and safety of treating progressive MS patients with autologous EBV-specific T cell therapy.\n                  <\/jats:p>\n                  <jats:p>\n                    <jats:bold>METHODS.<\/jats:bold>\n                    An open-label phase I trial was designed to treat 5 patients with secondary progressive MS and 5 patients with primary progressive MS with 4 escalating doses of in vitro\u2013expanded autologous EBV-specific T cells targeting EBV nuclear antigen 1, latent membrane protein 1 (LMP1), and LMP2A. Following adoptive immunotherapy, we monitored the patients for safety and clinical responses.\n                  <\/jats:p>\n                  <jats:p>\n                    <jats:bold>RESULTS.<\/jats:bold>\n                    Of the 13 recruited participants, 10 received the full course of T cell therapy. There were no serious adverse events. Seven patients showed improvement, with 6 experiencing both symptomatic and objective neurological improvement, together with a reduction in fatigue, improved quality of life, and, in 3 patients, reduced intrathecal IgG production. All 6 patients receiving T cells with strong EBV reactivity showed clinical improvement, whereas only 1 of the 4 patients receiving T cells with weak EBV reactivity showed improvement (\n                    <jats:italic>\n                      <jats:italic>P<\/jats:italic>\n                    <\/jats:italic>\n                    = 0.033, Fisher\u2019s exact test).\n                  <\/jats:p>\n                  <jats:p>\n                    <jats:bold>CONCLUSION.<\/jats:bold>\n                    EBV-specific adoptive T cell therapy was well tolerated. Clinical improvement following treatment was associated with the potency of EBV-specific reactivity of the administered T cells. Further clinical trials are warranted to determine the efficacy of EBV-specific T cell therapy in MS.\n                  <\/jats:p>\n                  <jats:p>\n                    <jats:bold>TRIAL REGISTRATION.<\/jats:bold>\n                    Australian New Zealand Clinical Trials Registry, ACTRN12615000422527.\n                  <\/jats:p>\n                  <jats:p>\n                    <jats:bold>FUNDING.<\/jats:bold>\n                    MS Queensland, MS Research Australia, Perpetual Trustee Company Ltd., and donations from private individuals who wish to remain anonymous.\n                  <\/jats:p>","DOI":"10.1172\/jci.insight.124714","type":"journal-article","created":{"date-parts":[[2018,11,14]],"date-time":"2018-11-14T11:01:38Z","timestamp":1542193298000},"source":"Crossref","is-referenced-by-count":147,"title":["Epstein-Barr virus\u2013specific T cell therapy for progressive multiple sclerosis"],"prefix":"10.1172","volume":"3","author":[{"given":"Michael P.","family":"Pender","sequence":"first","affiliation":[{"name":"Faculty of Medicine, The University of Queensland, Brisbane, Queensland, Australia."},{"name":"Department of Neurology, Royal Brisbane and Women\u2019s Hospital, Brisbane, Queensland, Australia."},{"name":"QIMR Berghofer Centre for Immunotherapy and Vaccine Development, QIMR Berghofer Medical Research Institute, Brisbane, Queensland, Australia."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Peter A.","family":"Csurhes","sequence":"additional","affiliation":[{"name":"Faculty of Medicine, The University of Queensland, Brisbane, Queensland, Australia."},{"name":"The University of Queensland Centre for Clinical Research, Brisbane, Queensland, Australia."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Corey","family":"Smith","sequence":"additional","affiliation":[{"name":"QIMR Berghofer Centre for Immunotherapy and Vaccine Development, QIMR Berghofer Medical Research Institute, Brisbane, Queensland, Australia."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nanette L.","family":"Douglas","sequence":"additional","affiliation":[{"name":"Faculty of Medicine, The University of Queensland, Brisbane, Queensland, Australia."},{"name":"Department of Neurology, Royal Brisbane and Women\u2019s Hospital, Brisbane, Queensland, Australia."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michelle A.","family":"Neller","sequence":"additional","affiliation":[{"name":"QIMR Berghofer Centre for Immunotherapy and Vaccine Development, QIMR Berghofer Medical Research Institute, Brisbane, Queensland, Australia."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Katherine K.","family":"Matthews","sequence":"additional","affiliation":[{"name":"QIMR Berghofer Centre for Immunotherapy and Vaccine Development, QIMR Berghofer Medical Research Institute, Brisbane, Queensland, Australia."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Leone","family":"Beagley","sequence":"additional","affiliation":[{"name":"QIMR Berghofer Centre for Immunotherapy and Vaccine Development, QIMR Berghofer Medical Research Institute, Brisbane, Queensland, Australia."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sweera","family":"Rehan","sequence":"additional","affiliation":[{"name":"QIMR Berghofer Centre for Immunotherapy and Vaccine Development, QIMR Berghofer Medical Research Institute, Brisbane, Queensland, Australia."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Pauline","family":"Crooks","sequence":"additional","affiliation":[{"name":"QIMR Berghofer Centre for Immunotherapy and Vaccine Development, QIMR Berghofer Medical Research Institute, Brisbane, Queensland, Australia."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tracey J.","family":"Hopkins","sequence":"additional","affiliation":[{"name":"Internal Medicine Day Treatment Unit, Royal Brisbane and Women\u2019s Hospital, Brisbane, Queensland, Australia."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Stefan","family":"Blum","sequence":"additional","affiliation":[{"name":"Faculty of Medicine, The University of Queensland, Brisbane, Queensland, Australia."},{"name":"Department of Neurology, Royal Brisbane and Women\u2019s Hospital, Brisbane, Queensland, Australia."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kerryn A.","family":"Green","sequence":"additional","affiliation":[{"name":"Faculty of Medicine, The University of Queensland, Brisbane, Queensland, Australia."},{"name":"Department of Neurology, Royal Brisbane and Women\u2019s Hospital, Brisbane, Queensland, Australia."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zara A.","family":"Ioannides","sequence":"additional","affiliation":[{"name":"Faculty of Medicine, The University of Queensland, Brisbane, Queensland, Australia."},{"name":"Department of Neurology, Royal Brisbane and Women\u2019s Hospital, Brisbane, Queensland, Australia."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Andrew","family":"Swayne","sequence":"additional","affiliation":[{"name":"Faculty of Medicine, The University of Queensland, Brisbane, Queensland, Australia."},{"name":"Department of Neurology, Royal Brisbane and Women\u2019s Hospital, Brisbane, Queensland, Australia."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4020-2718","authenticated-orcid":true,"given":"Blake T.","family":"Aftab","sequence":"additional","affiliation":[{"name":"Preclinical Science and Translational Medicine, Atara Biotherapeutics, South San Francisco, California, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kaye D.","family":"Hooper","sequence":"additional","affiliation":[{"name":"Faculty of Medicine, The University of Queensland, Brisbane, Queensland, Australia."},{"name":"Department of Neurology, Royal Brisbane and Women\u2019s Hospital, Brisbane, Queensland, Australia."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Scott R.","family":"Burrows","sequence":"additional","affiliation":[{"name":"Faculty of Medicine, The University of Queensland, Brisbane, Queensland, Australia."},{"name":"QIMR Berghofer Centre for Immunotherapy and Vaccine Development, QIMR Berghofer Medical Research Institute, Brisbane, Queensland, Australia."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kate M.","family":"Thompson","sequence":"additional","affiliation":[{"name":"Department of Psychology, Royal Brisbane and Women\u2019s Hospital, Brisbane, Queensland, Australia."},{"name":"Faculty of Health and Behavioural Sciences, The University of Queensland, Brisbane, Queensland, Australia."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1110-9207","authenticated-orcid":true,"given":"Alan","family":"Coulthard","sequence":"additional","affiliation":[{"name":"Faculty of Medicine, The University of Queensland, Brisbane, Queensland, Australia."},{"name":"Department of Medical Imaging, Royal Brisbane and Women\u2019s Hospital, Brisbane,Queensland, Australia."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2241-0353","authenticated-orcid":true,"given":"Rajiv","family":"Khanna","sequence":"additional","affiliation":[{"name":"Faculty of Medicine, The University of Queensland, Brisbane, Queensland, Australia."},{"name":"QIMR Berghofer Centre for Immunotherapy and Vaccine Development, QIMR Berghofer Medical Research Institute, Brisbane, Queensland, Australia."}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"232","published-online":{"date-parts":[[2018,11,15]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","DOI":"10.1038\/nrneurol.2012.198"},{"key":"B2","doi-asserted-by":"publisher","DOI":"10.1038\/cti.2014.25"},{"key":"B3","doi-asserted-by":"publisher","DOI":"10.1177\/1352458512449682"},{"key":"B4","doi-asserted-by":"publisher","DOI":"10.1001\/archneur.1980.00500510052009"},{"issue":"6","key":"B5","doi-asserted-by":"crossref","first-page":"824","DOI":"10.1002\/ana.21978","article-title":"Primary infection with the Epstein-Barr virus and risk of multiple sclerosis","volume":"67","author":"Levin","year":"2010","journal-title":"Ann Neurol"},{"key":"B6","doi-asserted-by":"publisher","DOI":"10.1146\/annurev.micro.54.1.19"},{"key":"B7","doi-asserted-by":"publisher","DOI":"10.1016\/j.it.2003.09.005"},{"key":"B8","doi-asserted-by":"publisher","DOI":"10.1084\/jem.20071030"},{"key":"B9","doi-asserted-by":"publisher","DOI":"10.1212\/WNL.0b013e31823ed057"},{"key":"B10","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0192109"},{"key":"B11","doi-asserted-by":"publisher","DOI":"10.1212\/NXI.0000000000000466"},{"issue":"Pt 12","key":"B12","doi-asserted-by":"crossref","first-page":"3318","DOI":"10.1093\/brain\/awp200","article-title":"Epstein-Barr virus infection is not a characteristic feature of multiple sclerosis brain","volume":"132","author":"Willis","year":"2009","journal-title":"Brain"},{"issue":"Pt 5","key":"B13","article-title":"Epstein Barr virus is not a characteristic feature in the central nervous system in established multiple sclerosis","volume":"133","author":"Peferoen","year":"2010","journal-title":"Brain"},{"key":"B14","doi-asserted-by":"publisher","DOI":"10.1177\/1073858410381531"},{"key":"B15","doi-asserted-by":"publisher","DOI":"10.1136\/jnnp.2008.161018"},{"key":"B16","doi-asserted-by":"publisher","DOI":"10.1038\/cti.2016.87"},{"key":"B17","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.177.7.4897"},{"key":"B18","doi-asserted-by":"publisher","DOI":"10.1158\/0008-5472.CAN-11-3399"},{"key":"B19","doi-asserted-by":"publisher","DOI":"10.1097\/NEN.0b013e3181e332ec"},{"key":"B20","doi-asserted-by":"publisher","DOI":"10.1177\/1352458514521888"},{"key":"B21","doi-asserted-by":"publisher","DOI":"10.1212\/WNL.33.11.1444"},{"key":"B22","doi-asserted-by":"publisher","DOI":"10.1001\/archneur.1989.00520460115022"},{"key":"B23","doi-asserted-by":"publisher","DOI":"10.1007\/s12160-010-9236-y"},{"key":"B24","doi-asserted-by":"publisher","DOI":"10.1017\/S0317167100014384"},{"key":"B25","doi-asserted-by":"publisher","DOI":"10.1007\/s10072-016-2578-x"},{"key":"B26","unstructured":"Beck A, Steer R, Brown G. BDI-Fast Screen for Medical Patients: Manual. Pearson Clinical. https:\/\/www.pearsonclinical.com\/psychology\/products\/100000173\/bdi--fastscreen-for-medical-patients-bdi.html Accessed October 25, 2018"},{"key":"B27","doi-asserted-by":"publisher","DOI":"10.1177\/1352458506070926"},{"key":"B28","doi-asserted-by":"publisher","DOI":"10.1177\/1352458513477924"},{"key":"B29","doi-asserted-by":"publisher","DOI":"10.1097\/NEN.0000000000000082"},{"key":"B30","doi-asserted-by":"publisher","DOI":"10.1002\/ana.22366"},{"key":"B31","doi-asserted-by":"publisher","DOI":"10.1016\/0009-8981(87)90250-6"},{"key":"B32","doi-asserted-by":"publisher","DOI":"10.1159\/000116920"}],"container-title":["JCI Insight"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/insight.jci.org\/articles\/view\/124714\/files\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,5,19]],"date-time":"2026-05-19T12:39:07Z","timestamp":1779194347000},"score":1,"resource":{"primary":{"URL":"https:\/\/insight.jci.org\/articles\/view\/124714"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2018,11,15]]},"references-count":32,"journal-issue":{"issue":"22","published-online":{"date-parts":[[2018,11,15]]},"published-print":{"date-parts":[[2018,11,15]]}},"alternative-id":["10.1172\/jci.insight.124714"],"URL":"https:\/\/doi.org\/10.1172\/jci.insight.124714","relation":{"has-review":[{"id-type":"doi","id":"10.3410\/f.734448917.793568400","asserted-by":"object"}]},"ISSN":["2379-3708"],"issn-type":[{"value":"2379-3708","type":"electronic"}],"subject":[],"published":{"date-parts":[[2018,11,15]]},"article-number":"e124714"}}