Adoptive JC Virus-Specific T Lymphocytes for the Treatment of Progressive Multifocal Leukoencephalopathy: Experience from Two Italian Centers

• Published in: Viruses Vol. 17; no. 7; p. 934
• Main Authors: Pocora, Maria Magdalena, Bini, Paola, Berzero, Giulia, Vegezzi, Elisa, Diamanti, Luca, Gastaldi, Matteo, Cinque, Paola, Catalano, Gaia, Paoletti, Matteo, Pichiecchio, Anna, Tartara, Fulvio, Basso, Sabrina, Baldanti, Fausto, Furione, Milena, Comoli, Patrizia, Marchioni, Enrico
• Format: Journal Article
• Language: English
• Published: Switzerland MDPI AG 30.06.2025; MDPI
• Subjects: adoptive T cell therapy; Adult; Aged; Aphasia; Ataxia; Biomarkers; Care and treatment; Chicken pox; Diagnosis; Disability; Disease; Female; Good Manufacturing Practice; Health aspects; HIV; Human immunodeficiency virus; Humans; Immune reconstitution; Immune system; Immunotherapy, Adoptive - methods; Italy; JC Virus - immunology; JCV; Leukemia; Leukocytes (mononuclear); Leukoencephalopathy; Leukoencephalopathy, Progressive Multifocal - immunology; Leukoencephalopathy, Progressive Multifocal - therapy; Leukoencephalopathy, Progressive Multifocal - virology; Lymphocytes; Lymphocytes T; Lymphoma; Magnetic Resonance Imaging; Male; Middle Aged; Neuroimaging; Patients; Peptides; Peripheral blood mononuclear cells; Progressive multifocal leukoencephalopathy; Stem cell transplantation; T cells; T-Lymphocytes - immunology; T-Lymphocytes - transplantation; Treatment Outcome; Italy; JCV; progressive multifocal leukoencephalopathy; adoptive T cell therapy
• ISSN: 1999-4915; 1999-4915
• DOI: 10.3390/v17070934

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 “definite PML” 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.