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Updated: Aug 13, 2026
Generation of Multivirus-specific T Cells to Prevent/treat Viral Infections after Allogeneic Hematopoietic Stem Cell Transplant
Published on: May 27, 2011
BK virus-specific T cells for immunotherapy of progressive multifocal leukoencephalopathy: an open-label,
Irene Cortese1, Erin S Beck2, Omar Al-Louzi2
1Neuroimmunology Clinic, National Institutes of Health, Bethesda, MD, USA.
Insights
This study shows that using BK virus-specific T cells from related donors is a safe and feasible adoptive immunotherapy for progressive multifocal leukoencephalopathy (PML). This approach offers potential life-saving benefits for patients with this rare CNS disease.
Area of Science:
- Immunology
- Neurology
- Virology
Background:
- Progressive multifocal leukoencephalopathy (PML) is a fatal CNS disease caused by JC virus in immunosuppressed individuals.
- JC virus is closely related to BK virus, a human polyomavirus.
- Restoring adaptive immunity is key to survival in PML.
Purpose of the Study:
- To assess the feasibility and safety of using HLA-matched donor-derived BK virus-specific T cells for adoptive immunotherapy in PML patients.
- To evaluate the potential of this T cell therapy to restore anti-viral immunity against JC virus.
Main Methods:
- An open-label, single-cohort pilot study involving 12 eligible PML patients.
- Generation of polyomavirus-specific T cells from first-degree relative donors, cross-recognizing JC virus.
- Intravenous infusion of T cells, with doses escalated in subsequent infusions if tolerated.
- Monitoring for feasibility, safety, and clinical outcomes via MRI for up to 12 months.
Main Results:
- All infused T cells met release criteria and demonstrated in vitro antiviral activity.
- No serious treatment-related adverse events were observed; infusions were well-tolerated.
- Seven of twelve patients survived PML for over a year; five died within three months.
Conclusions:
- The generation and administration of polyomavirus-specific T cells are feasible and safe for PML immunotherapy.
- This strategy shows promise as a potential life-saving therapy for PML, warranting further investigation.
- The study provides evidence supporting T cell therapy for JC virus-induced PML.
Background:
Progressive multifocal leukoencephalopathy, a rare disease of the CNS caused by JC virus and occurring in immunosuppressed people, is typically fatal unless adaptive immunity is restored. JC virus is a member of the human polyomavirus family and is closely related to the BK virus. We hypothesised that use of partly HLA-matched donor-derived BK virus-specific T cells for immunotherapy in progressive multifocal leukoencephalopathy would be feasible and safe.
Methods:
We did an open-label, single-cohort pilot study in patients (aged 18 years or older) with clinically definite progressive multifocal leukoencephalopathy and disease progression in the previous month at the National Institutes of Health (NIH) Clinical Center (Bethesda, MD, USA). Overlapping peptide libraries derived from large T antigen and major capsid protein VP1 of BK virus with high sequence homology to JC virus counterparts were used to generate polyomavirus-specific T cells cross-recognising JC virus antigens. Polyomavirus-specific T cells were manufactured from peripheral blood mononuclear cells of first-degree relative donors aged 18 years or older. These cells were administered to patients by intravenous infusion at 1 × 106 polyomavirus-specific T cells per kg, followed by up to two additional infusions at 2 × 106 polyomavirus-specific T cells per kg. The primary endpoints were feasibility (no manufacturing failure based on meeting release criteria, achieving adequate numbers of cell product for clinical use, and showing measurable antiviral activity) and safety in all patients. The safety monitoring period was 28 days after each infusion. Patients were followed up with serial MRI for up to 12 months after the final infusion. This trial is registered at ClinicalTrials.gov, NCT02694783.
Findings:
Between April 7, 2016, and Oct 19, 2018, 26 patients were screened, of whom 12 were confirmed eligible and received treatment derived from 14 matched donors. All administered polyomavirus-specific T cells met the release criteria and recognised cognate antigens in vitro. 12 patients received at least one infusion, ten received at least two, and seven received a total of three infusions. The median on-study follow-up was 109·5 days (range 23-699). All infusions were tolerated well, and no serious treatment-related adverse events were observed. Seven patients survived progressive multifocal leukoencephalopathy for longer than 1 year after the first infusion, whereas five died of progressive multifocal leukoencephalopathy within 3 months.
Interpretation:
We showed that generation of polyomavirus-specific T cells from healthy related donors is feasible, and these cells can be safely used as an infusion for adoptive immunotherapy of progressive multifocal leukoencephalopathy. Although not powered to assess efficacy, our data provide additional support for this strategy as a potential life-saving therapy for some patients.
Funding:
Intramural Research Program of the National Institute of Neurological Disorders and Stroke of the NIH.
