Evidence map›Paper›PMID 34302788›Full record

ArticleThe Lancet. Neurology2021

BK virus-specific T cells for immunotherapy of progressive multifocal leukoencephalopathy: an open-label, single-cohort pilot study.

Irene Cortese, Erin S Beck, Omar Al-Louzi, Joan Ohayon, Frances Andrada, Ikesinachi Osuorah, Jenifer Dwyer, B Jeanne Billioux, Nigar Dargah-Zada, Matthew K Schindler and 15 more

Open access · greenAbstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in The Lancet. Neurology, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 32 papers.

0numbers the graph read from it
0cells of the map it votes in
32citing papers in PubMed
4.1field-weighted citation impact, top 4% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

32 citing papers in PubMed, 59 citations in OpenAlex.

  1. Trial
  2. Article
  3. Adoptive T-cell therapy for virus-associated diseases.Clinical microbiology reviews · 2025
    Review
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  5. Article
  6. JC Polyomavirus Infection: A Narrative Review.Infectious diseases and therapy · 2025
    Review
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  8. Article
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  10. Virus-Specific T-Cell Therapy for the Management of Viral Infections in the Immunocompromised.Transfusion medicine and hemotherapy : offizielles Organ der Deutschen Gesellschaft fur Transfusionsmedizin und Immunhamatologie · 2025
    Review
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4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

25 authors at 4 institutions in 1 country.

Irene CorteseNeuroimmunology Clinic, National Institutes of Health, Bethesda, MD, USA. Electronic address: corteseir@ninds.nih.gov.
Erin S BeckTranslational Neuroradiology Section, National Institutes of Health, Bethesda, MD, USA.
Omar Al-LouziTranslational Neuroradiology Section, National Institutes of Health, Bethesda, MD, USA.
Joan OhayonNeuroimmunology Clinic, National Institutes of Health, Bethesda, MD, USA.
Frances AndradaNeuroimmunology Clinic, National Institutes of Health, Bethesda, MD, USA.
Ikesinachi OsuorahNeuroimmunology Clinic, National Institutes of Health, Bethesda, MD, USA.
Jenifer DwyerNeuroimmunology Clinic, National Institutes of Health, Bethesda, MD, USA.
B Jeanne BilliouxViral Immunology Section, National Institutes of Health, Bethesda, MD, USA.
Nigar Dargah-ZadaNeuroimmunology Clinic, National Institutes of Health, Bethesda, MD, USA.
Matthew K SchindlerTranslational Neuroradiology Section, National Institutes of Health, Bethesda, MD, USA.
Kyle BinderNational Institute of Neurological Disorders and Stroke, and Molecular Development of the Immune System Section, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD, USA.
Lauren ReomaClinical Trials Unit, National Institutes of Health, Bethesda, MD, USA.
Gina NoratoClinical Trials Unit, National Institutes of Health, Bethesda, MD, USA.
Yoshimi Enose-AkahataViral Immunology Section, National Institutes of Health, Bethesda, MD, USA.
Bryan R SmithSection of Infections of the Nervous System, National Institutes of Health, Bethesda, MD, USA.
Maria Chiara MonacoLaboratory of Molecular Medicine and Neuroscience, National Institutes of Health, Bethesda, MD, USA.
Eugene O MajorLaboratory of Molecular Medicine and Neuroscience, National Institutes of Health, Bethesda, MD, USA.
Steven JacobsonViral Immunology Section, National Institutes of Health, Bethesda, MD, USA.
David StroncekCenter for Cellular Engineering, Department of Transfusion Medicine, National Institutes of Health, Bethesda, MD, USA.
Steven HighfillCenter for Cellular Engineering, Department of Transfusion Medicine, National Institutes of Health, Bethesda, MD, USA.
Sandhya PanchCenter for Cellular Engineering, Department of Transfusion Medicine, National Institutes of Health, Bethesda, MD, USA.
Daniel S ReichTranslational Neuroradiology Section, National Institutes of Health, Bethesda, MD, USA.
John BarrettHematology Branch, Heart, Lung, and Blood Institute, National Institutes of Health, Bethesda, MD, USA; George Washington University Cancer Center, George Washington University, Washington, DC, USA.
Avindra NathSection of Infections of the Nervous System, National Institutes of Health, Bethesda, MD, USA.
Pawel MuranskiHematology Branch, Heart, Lung, and Blood Institute, National Institutes of Health, Bethesda, MD, USA; Herbert Irving Comprehensive Cancer Center, Columbia University Medical Center, New York, NY, USA.
National Institutes of Health · USNational Institutes of Health Clinical Center · USNational Heart Lung and Blood Institute · USNational Institute of Neurological Disorders and Stroke · US

Funding

NINDS Office of the Clinical DirectorZIDNS003101 · NINDS · NATIONAL INSTITUTE OF NEUROLOGICAL DISORDERS AND STROKE · PI NATH, AVINDRA · 2009 to 2025
$219.6M
Multimodal MRI in Multiple SclerosisZIANS003119 · NINDS · NATIONAL INSTITUTE OF NEUROLOGICAL DISORDERS AND STROKE · PI REICH, DANIEL · 2010 to 2025
$53.4M
Studies of Occupational CancerZIACP010120 · NCI · DIVISION OF CANCER EPIDEMIOLOGY AND GENETICS · PI LAN, QING · 2009 to 2025
$34.4M
Translational studies of human viruses and chronic neurologic diseaseZIANS003040 · NINDS · NATIONAL INSTITUTE OF NEUROLOGICAL DISORDERS AND STROKE · PI JACOBSON, STEVEN · 2009 to 2025
$10.1M
Translational Studies in Progressive Multifocal LeukoencephalopathyZIANS009426 · NINDS · NATIONAL INSTITUTE OF NEUROLOGICAL DISORDERS AND STROKE · PI CORTESE, IRENE · 2021 to 2025
$7.5M
Immunophenotyping by high-dimensional cytometry and machine learningZIABC011807 · NCI · DIVISION OF BASIC SCIENCES - NCI · PI ALTAN-BONNET, GRÉGOIRE · 2018 to 2025
$3.6M
Development of novel cell and gene therapiesZIACL002120 · CLC · CLINICAL CENTER · PI STRONCEK, DAVID · 2009 to 2025
$0k
Intramural NIH HHS Z99 NS999999Intramural NIH HHS ZID NS003101
6 · The paper itself

Abstract

backgroundProgressive 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.

methodsWe 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 × 10

findingsBetween 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.

interpretationWe 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.

fundingIntramural Research Program of the National Institute of Neurological Disorders and Stroke of the NIH.

Indexed as

AdultAgedBK VirusBlood DonorsCohort StudiesEndpoint DeterminationFeasibility StudiesFemaleHumansImmunotherapyJC VirusLeukoencephalopathy, Progressive MultifocalMagnetic Resonance ImagingMaleMiddle AgedMonocytes

Identifiers

PMID34302788
PMCPMC8395368
OpenAlexW3186556934

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Registered trials

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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.