Evidence map›Paper›PMID 39011042›Full record

ArticleFrontiers in immunology2024

EBV T-cell immunotherapy generated by peptide selection has enhanced effector functionality compared to LCL stimulation.

Rachel S Cooper, Catherine Sutherland, Linda M Smith, Graeme Cowan, Mark Barnett, Donna Mitchell, Colin McLean, Stuart Imlach, Alan Hayes, Sharon Zahra and 7 more

Abstract read
In one paragraph

Article in Frontiers in immunology, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 3 papers.

0numbers the graph read from it
0cells of the map it votes in
3citing papers in PubMed
–field-weighted citation impact
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

3 citing papers in PubMed.

  1. Review
  2. Article
  3. Article
4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

17 authors.

Rachel S CooperTissues, Cells and Advanced Therapeutics, Scottish National Blood Transfusion Service, Jack Copland Centre, Heriot Watt Research Park, Edinburgh, United Kingdom.
Catherine SutherlandInstitute of Immunology and Infection Research, School of Biological Sciences, University of Edinburgh, Edinburgh, United Kingdom.
Linda M SmithTissues, Cells and Advanced Therapeutics, Scottish National Blood Transfusion Service, Jack Copland Centre, Heriot Watt Research Park, Edinburgh, United Kingdom.
Graeme CowanInstitute of Immunology and Infection Research, School of Biological Sciences, University of Edinburgh, Edinburgh, United Kingdom.
Mark BarnettTissues, Cells and Advanced Therapeutics, Scottish National Blood Transfusion Service, Jack Copland Centre, Heriot Watt Research Park, Edinburgh, United Kingdom.
Donna MitchellTissues, Cells and Advanced Therapeutics, Scottish National Blood Transfusion Service, Jack Copland Centre, Heriot Watt Research Park, Edinburgh, United Kingdom.
Colin McLeanTissues, Cells and Advanced Therapeutics, Scottish National Blood Transfusion Service, Jack Copland Centre, Heriot Watt Research Park, Edinburgh, United Kingdom.
Stuart ImlachTissues, Cells and Advanced Therapeutics, Scottish National Blood Transfusion Service, Jack Copland Centre, Heriot Watt Research Park, Edinburgh, United Kingdom.
Alan HayesChemokine Research Group, Institute of Infection, Immunity and Inflammation, University of Glasgow, Glasgow, United Kingdom.
Sharon ZahraTissues, Cells and Advanced Therapeutics, Scottish National Blood Transfusion Service, Jack Copland Centre, Heriot Watt Research Park, Edinburgh, United Kingdom.
Champa ManchanayakeTissues, Cells and Advanced Therapeutics, Scottish National Blood Transfusion Service, Jack Copland Centre, Heriot Watt Research Park, Edinburgh, United Kingdom.
Mark A VickersBlood Transfusion Centre, Scottish National Blood Transfusion Service, Aberdeen, United Kingdom.
Gerry GrahamChemokine Research Group, Institute of Infection, Immunity and Inflammation, University of Glasgow, Glasgow, United Kingdom.
Neil W A McGowanTissues, Cells and Advanced Therapeutics, Scottish National Blood Transfusion Service, Jack Copland Centre, Heriot Watt Research Park, Edinburgh, United Kingdom.
Marc L TurnerTissues, Cells and Advanced Therapeutics, Scottish National Blood Transfusion Service, Jack Copland Centre, Heriot Watt Research Park, Edinburgh, United Kingdom.
John D M CampbellTissues, Cells and Advanced Therapeutics, Scottish National Blood Transfusion Service, Jack Copland Centre, Heriot Watt Research Park, Edinburgh, United Kingdom.
Alasdair R FraserTissues, Cells and Advanced Therapeutics, Scottish National Blood Transfusion Service, Jack Copland Centre, Heriot Watt Research Park, Edinburgh, United Kingdom.

Funding

Wellcome Trust 220096/Z/20/Z
6 · The paper itself

Abstract

Adoptive immunotherapy with Epstein-Barr virus (EBV)-specific T cells is an effective treatment for relapsed or refractory EBV-induced post-transplant lymphoproliferative disorders (PTLD) with overall survival rates of up to 69%. EBV-specific T cells have been conventionally made by repeated stimulation with EBV-transformed lymphoblastoid cell lines (LCL), which act as antigen-presenting cells. However, this process is expensive, takes many months, and has practical risks associated with live virus. We have developed a peptide-based, virus-free, serum-free closed system to manufacture a bank of virus-specific T cells (VST) for clinical use. We compared these with standard LCL-derived VST using comprehensive characterization and potency assays to determine differences that might influence clinical benefits. Multi-parameter flow cytometry revealed that peptide-derived VST had an expanded central memory population and less exhaustion marker expression than LCL-derived VST. A quantitative HLA-matched allogeneic cytotoxicity assay demonstrated similar specific killing of EBV-infected targets, though peptide-derived EBV T cells had a significantly higher expression of antiviral cytokines and degranulation markers after antigen recall. High-throughput T cell receptor-beta (TCRβ) sequencing demonstrated oligoclonal repertoires, with more matches to known EBV-binding complementary determining region 3 (CDR3) sequences in peptide-derived EBV T cells. Peptide-derived products showed broader and enhanced specificities to EBV nuclear antigens (EBNAs) in both CD8 and CD4 compartments, which may improve the targeting of highly expressed latency antigens in PTLD. Importantly, peptide-based isolation and expansion allows rapid manufacture and significantly increased product yield over conventional LCL-based approaches.

Indexed as

Epstein-Barr Virus InfectionsHerpesvirus 4, HumanImmunotherapy, AdoptivePeptidesCell Line, TransformedHumansLymphocyte ActivationT-LymphocytesPeptidescell therapyEpstein-Barr virusimmunotherapylymphoblastoid cell linepeptidepotencyT cellT cell receptor

Identifiers

PMID39011042
PMCPMC11246990

What Socratic holds

Textmetadata
LicenceCC BY
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 Socratic graph.