Adoptive Transfer of JC Virus-Specific T Lymphocytes for the Treatment of Progressive Multifocal Leukoencephalopathy
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Updated: Nov 21, 2025

Expanding Cytotoxic T Lymphocytes from Umbilical Cord Blood that Target Cytomegalovirus, Epstein-Barr Virus, and Adenovirus
Published on: May 7, 2012
Giulia Berzero1,2, Sabrina Basso3,4, Luca Stoppini3,4
1Neuroncology Unit, IRCCS Mondino Foundation, Pavia, Italy.
Objective:
Progressive multifocal leukoencephalopathy (PML) is still burdened by high mortality in a subset of patients, such as those affected by hematological malignancies. The aim of this study was to analyze the safety and carry out preliminary evaluation of the efficacy of polyomavirus JC (JCPyV)-specific T cell therapy in a cohort of hematological patients with PML.
Methods:
Between 2014 and 2019, 9 patients with a diagnosis of "definite PML" according to the 2013 consensus who were showing progressive clinical deterioration received JCPyV-specific T cells. Cell lines were expanded from autologous or allogenic peripheral blood mononuclear cells by stimulation with JCPyV antigen-derived peptides.
Results:
None of the patients experienced treatment-related adverse events. In the evaluable patients, an increase in the frequency of circulating JCPyV-specific lymphocytes was observed, with a decrease or clearance of JCPyV viral load in cerebrospinal fluid. In responsive patients, transient appearance of punctate areas of contrast enhancement within, or close to, PML lesions was observed, which was interpreted as a sign of immune control and which regressed spontaneously without the need for steroid treatment. Six of 9 patients achieved PML control, with 5 alive and in good clinical condition at their last follow-up.
Interpretation:
Among other novel treatments, T cell therapy is emerging as a viable treatment option in patients with PML, particularly for those not amenable to restoration of specific immunity. Neurologists should be encouraged to refer PML patients to specialized centers to allow access to this treatment strategy. ANN NEUROL 2021;89:769-779.
Insights
Polyomavirus JC (JCPyV)-specific T cell therapy shows promise for treating progressive multifocal leukoencephalopathy (PML) in hematological patients. This safe therapy led to PML control in most patients, with some achieving viral clearance and good clinical outcomes.
Area of Science:
- Immunology
- Neurology
- Oncology
Background:
- Progressive multifocal leukoencephalopathy (PML) presents a high mortality rate, especially in patients with hematological malignancies.
- Current treatment options for PML are limited, particularly for those unable to restore specific immunity.
Purpose of the Study:
- To evaluate the safety and preliminary efficacy of polyomavirus JC (JCPyV)-specific T cell therapy.
- To assess treatment outcomes in hematological patients diagnosed with PML.
Main Methods:
- Nine patients with definite PML and progressive clinical deterioration received JCPyV-specific T cells between 2014 and 2019.
- T cell lines were generated from autologous or allogeneic peripheral blood mononuclear cells stimulated with JCPyV antigen-derived peptides.
Main Results:
- No treatment-related adverse events were reported.
- Increased JCPyV-specific lymphocytes and decreased/cleared JCPyV viral load in cerebrospinal fluid were observed in evaluable patients.
- Six of nine patients achieved PML control, with five remaining alive and in good clinical condition.
Conclusions:
- JCPyV-specific T cell therapy is a safe and potentially effective treatment for PML in hematological patients.
- This approach offers a viable therapeutic strategy for PML patients unresponsive to other treatments.
- Referral to specialized centers is recommended for PML patients to access T cell therapy.
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