Evidence map›Paper›PMID 30429369›Full record

ArticleJCI insight2018

Epstein-Barr virus-specific T cell therapy for progressive multiple sclerosis.

Michael P Pender, Peter A Csurhes, Corey Smith, Nanette L Douglas, Michelle A Neller, Katherine K Matthews, Leone Beagley, Sweera Rehan, Pauline Crooks, Tracey J Hopkins and 10 more

Erratum issuedOpen access · goldAbstract readClinical Trial, Phase I
PubMed Full text at PMC Publisher
In one paragraph

Article in JCI insight, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. An erratum has been issued. Cited by 84 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
84citing papers in PubMed, 1 pooled it
8.6field-weighted citation impact, top 1% 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

84 citing papers in PubMed, 1 synthesis or guideline pooled it, 153 citations in OpenAlex.

  1. Pooled it
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  7. Article
  8. Article
  9. Article
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  14. Adoptive T-cell therapy for virus-associated diseases.Clinical microbiology reviews · 2025
    Review
  15. Article
  16. Review
  17. Review
  18. Article
  19. Multiple sclerosis and infection: history, EBV, and the search for mechanism.Microbiology and molecular biology reviews : MMBR · 2025
    Review
  20. Article

24 more citing papers are in PubMed but not listed here.

4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

20 authors at 4 institutions in 2 countries.

Michael P PenderFaculty of Medicine, The University of Queensland, Brisbane, Queensland, Australia.
Peter A CsurhesFaculty of Medicine, The University of Queensland, Brisbane, Queensland, Australia.
Corey SmithQIMR Berghofer Centre for Immunotherapy and Vaccine Development, QIMR Berghofer Medical Research Institute, Brisbane, Queensland, Australia.
Nanette L DouglasFaculty of Medicine, The University of Queensland, Brisbane, Queensland, Australia.
Michelle A NellerQIMR Berghofer Centre for Immunotherapy and Vaccine Development, QIMR Berghofer Medical Research Institute, Brisbane, Queensland, Australia.
Katherine K MatthewsQIMR Berghofer Centre for Immunotherapy and Vaccine Development, QIMR Berghofer Medical Research Institute, Brisbane, Queensland, Australia.
Leone BeagleyQIMR Berghofer Centre for Immunotherapy and Vaccine Development, QIMR Berghofer Medical Research Institute, Brisbane, Queensland, Australia.
Sweera RehanQIMR Berghofer Centre for Immunotherapy and Vaccine Development, QIMR Berghofer Medical Research Institute, Brisbane, Queensland, Australia.
Pauline CrooksQIMR Berghofer Centre for Immunotherapy and Vaccine Development, QIMR Berghofer Medical Research Institute, Brisbane, Queensland, Australia.
Tracey J HopkinsInternal Medicine Day Treatment Unit, Royal Brisbane and Women's Hospital, Brisbane, Queensland, Australia.
Stefan BlumFaculty of Medicine, The University of Queensland, Brisbane, Queensland, Australia.
Kerryn A GreenFaculty of Medicine, The University of Queensland, Brisbane, Queensland, Australia.
Zara A IoannidesFaculty of Medicine, The University of Queensland, Brisbane, Queensland, Australia.
Andrew SwayneFaculty of Medicine, The University of Queensland, Brisbane, Queensland, Australia.
Blake T AftabPreclinical Science and Translational Medicine, Atara Biotherapeutics, South San Francisco, California, USA.
Kaye D HooperFaculty of Medicine, The University of Queensland, Brisbane, Queensland, Australia.
Scott R BurrowsFaculty of Medicine, The University of Queensland, Brisbane, Queensland, Australia.
Kate M ThompsonDepartment of Psychology, Royal Brisbane and Women's Hospital, Brisbane, Queensland, Australia.
Alan CoulthardFaculty of Medicine, The University of Queensland, Brisbane, Queensland, Australia.
Rajiv KhannaFaculty of Medicine, The University of Queensland, Brisbane, Queensland, Australia.
The University of Queensland · AUQIMR Berghofer Medical Research Institute · AUAtara Biotherapeutics (United States) · USRoyal Brisbane and Women's Hospital · AU

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

backgroundIncreasing evidence indicates a role for EBV in the pathogenesis of multiple sclerosis (MS). EBV-infected autoreactive B cells might accumulate in the CNS because of defective cytotoxic CD8+ T cell immunity. We sought to determine the feasibility and safety of treating progressive MS patients with autologous EBV-specific T cell therapy.

methodsAn open-label phase I trial was designed to treat 5 patients with secondary progressive MS and 5 patients with primary progressive MS with 4 escalating doses of in vitro-expanded autologous EBV-specific T cells targeting EBV nuclear antigen 1, latent membrane protein 1 (LMP1), and LMP2A. Following adoptive immunotherapy, we monitored the patients for safety and clinical responses.

resultsOf the 13 recruited participants, 10 received the full course of T cell therapy. There were no serious adverse events. Seven patients showed improvement, with 6 experiencing both symptomatic and objective neurological improvement, together with a reduction in fatigue, improved quality of life, and, in 3 patients, reduced intrathecal IgG production. All 6 patients receiving T cells with strong EBV reactivity showed clinical improvement, whereas only 1 of the 4 patients receiving T cells with weak EBV reactivity showed improvement (P = 0.033, Fisher's exact test).

conclusionEBV-specific adoptive T cell therapy was well tolerated. Clinical improvement following treatment was associated with the potency of EBV-specific reactivity of the administered T cells. Further clinical trials are warranted to determine the efficacy of EBV-specific T cell therapy in MS.

trial registrationAustralian New Zealand Clinical Trials Registry, ACTRN12615000422527.

fundingMS Queensland, MS Research Australia, Perpetual Trustee Company Ltd., and donations from private individuals who wish to remain anonymous.

Indexed as

AdultAgedEpstein-Barr Virus Nuclear AntigensFemaleHerpesvirus 4, HumanHumansImmunotherapy, AdoptiveMagnetic Resonance ImagingMaleMiddle AgedMultiple SclerosisT-LymphocytesTreatment OutcomeViral Matrix ProteinsEBV-associated membrane antigen, Epstein-Barr virusEBV-encoded nuclear antigen 1Epstein-Barr Virus Nuclear AntigensViral Matrix ProteinsAutoimmune diseasesClinical TrialsNeuroscienceT cells

Identifiers

PMID30429369
PMCPMC6302936
OpenAlexW2900501647

What OpenQuestion holds

Textmetadata
Read underepoch 390

Registered trials

None linked

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.