{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,20]],"date-time":"2026-10-20T05:31:50Z","timestamp":1792474310906,"version":"4.5.0"},"reference-count":24,"publisher":"MDPI AG","issue":"7","license":[{"start":{"date-parts":[[2025,6,30]],"date-time":"2025-06-30T00:00:00Z","timestamp":1751241600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Ministero della Salute, Ricerca Corrente","award":["RCR 08071519"],"award-info":[{"award-number":["RCR 08071519"]}]},{"name":"Ministero della Salute, Ricerca Corrente","award":["RCR 08069113"],"award-info":[{"award-number":["RCR 08069113"]}]},{"name":"Ministero della Salute, Ricerca Corrente","award":["RF-2019-12371492"],"award-info":[{"award-number":["RF-2019-12371492"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Viruses"],"abstract":"<jats:p>Background: Progressive multifocal leukoencephalopathy (PML) is a rare but fatal disease caused by John Cunningham virus (JCV) in immunocompromised individuals, with no effective antiviral treatment currently available. This study aimed to evaluate the feasibility of adoptive JCV-specific T lymphocyte therapy in patients with PML. Methods: Nineteen patients meeting the 2013 consensus criteria for \u201cdefinite PML\u201d were included, and JCV-specific T lymphocytes expanded from autologous or allogeneic peripheral blood mononuclear cells (PBMCs) using JCV antigen-derived peptides were administered. Clinical outcomes were monitored through neuroimaging and biological markers. Results: The mean age at diagnosis was 56.5 years, with a mean time to treatment of three months. Patients received a median of two infusions. At 12 months, six patients (31.6%) survived, while 13 (68.4%) had died, primarily due to PML progression. Survivors had a higher median baseline Karnofsky performance scale (KPS) score (50% vs. 30%, p = 0.41) and a significantly shorter diagnosis delay. MRI assessment showed a reduced disease burden in survivors, and JCV-DNA copy numbers decreased overall. One case of immune reconstitution inflammatory syndrome (IRIS) was observed. Conclusions: Adoptive JCV-specific T lymphocytes may represent a safe therapeutic option for PML patients, and the MRI burden and JCV-DNA copy may serve as biomarkers for disease monitoring.<\/jats:p>","DOI":"10.3390\/v17070934","type":"journal-article","created":{"date-parts":[[2025,7,2]],"date-time":"2025-07-02T07:55:43Z","timestamp":1751442943000},"page":"934","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":9,"title":["Adoptive JC Virus-Specific T Lymphocytes for the Treatment of Progressive Multifocal Leukoencephalopathy: Experience from Two Italian Centers"],"prefix":"10.3390","volume":"17","author":[{"ORCID":"https:\/\/orcid.org\/0009-0006-1874-6611","authenticated-orcid":false,"given":"Maria Magdalena","family":"Pocora","sequence":"first","affiliation":[{"name":"Department of Brain and Behavioural Sciences, University of Pavia, 27100 Pavia, Italy"},{"name":"IRCCS Mondino Foundation, 27100 Pavia, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1612-6156","authenticated-orcid":false,"given":"Paola","family":"Bini","sequence":"additional","affiliation":[{"name":"Neuroncology Unit, IRCCS Mondino Foundation, 27100 Pavia, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8798-9058","authenticated-orcid":false,"given":"Giulia","family":"Berzero","sequence":"additional","affiliation":[{"name":"Neurology Unit, IRCCS Ospedale San Raffaele, 20132 Milan, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Elisa","family":"Vegezzi","sequence":"additional","affiliation":[{"name":"Neuroncology Unit, IRCCS Mondino Foundation, 27100 Pavia, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Luca","family":"Diamanti","sequence":"additional","affiliation":[{"name":"Neuroncology Unit, IRCCS Mondino Foundation, 27100 Pavia, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Matteo","family":"Gastaldi","sequence":"additional","affiliation":[{"name":"Neuroncology Unit, IRCCS Mondino Foundation, 27100 Pavia, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2448-5957","authenticated-orcid":false,"given":"Paola","family":"Cinque","sequence":"additional","affiliation":[{"name":"Unit of Infectious Diseases, IRCCS San Raffaele Scientific Institute, 20132 Milan, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0006-7039-2611","authenticated-orcid":false,"given":"Gaia","family":"Catalano","sequence":"additional","affiliation":[{"name":"Unit of Infectious Diseases, IRCCS San Raffaele Scientific Institute, 20132 Milan, Italy"},{"name":"School of Medicine, San Raffaele Vita-Salute University, 20132 Milan, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1221-7747","authenticated-orcid":false,"given":"Matteo","family":"Paoletti","sequence":"additional","affiliation":[{"name":"Advanced Imaging and Artificial Intelligence Center, Neuroradiology Department, IRCCS Mondino Foundation, 27100 Pavia, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5654-4088","authenticated-orcid":false,"given":"Anna","family":"Pichiecchio","sequence":"additional","affiliation":[{"name":"Department of Brain and Behavioural Sciences, University of Pavia, 27100 Pavia, Italy"},{"name":"Advanced Imaging and Artificial Intelligence Center, Neuroradiology Department, IRCCS Mondino Foundation, 27100 Pavia, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6131-9547","authenticated-orcid":false,"given":"Fulvio","family":"Tartara","sequence":"additional","affiliation":[{"name":"IRCCS Mondino Foundation, 27100 Pavia, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sabrina","family":"Basso","sequence":"additional","affiliation":[{"name":"Cell Factory, Fondazione IRCCS Policlinico San Matteo, 27100 Pavia, Italy"},{"name":"Pediatric Oncoematology Unit, Fondazione IRCCS Policlinico San Matteo, 27100 Pavia, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fausto","family":"Baldanti","sequence":"additional","affiliation":[{"name":"Microbiology and Virology, Fondazione IRCCS Policlinico San Matteo, 27100 Pavia, Italy"},{"name":"Department of Clinical-Surgical, Diagnostic and Pediatric Sciences, University of Pavia, 27100 Pavia, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Milena","family":"Furione","sequence":"additional","affiliation":[{"name":"Microbiology and Virology, Fondazione IRCCS Policlinico San Matteo, 27100 Pavia, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Patrizia","family":"Comoli","sequence":"additional","affiliation":[{"name":"Cell Factory, Fondazione IRCCS Policlinico San Matteo, 27100 Pavia, Italy"},{"name":"Pediatric Oncoematology Unit, Fondazione IRCCS Policlinico San Matteo, 27100 Pavia, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0414-8128","authenticated-orcid":false,"given":"Enrico","family":"Marchioni","sequence":"additional","affiliation":[{"name":"Neuroncology Unit, IRCCS Mondino Foundation, 27100 Pavia, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2025,6,30]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"865","DOI":"10.1002\/ana.26198","article-title":"Advances in Treatment of Progressive Multifocal Leukoencephalopathy","volume":"90","author":"Koralnik","year":"2021","journal-title":"Ann. 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