Evidence map›Paper›PMID 24204746›Full record

Trial reportPloS one2013

Production and first-in-man use of T cells engineered to express a HSVTK-CD34 sort-suicide gene.

Hong Zhan, Kimberly Gilmour, Lucas Chan, Farzin Farzaneh, Anne Marie McNicol, Jin-Hua Xu, Stuart Adams, Boris Fehse, Paul Veys, Adrian Thrasher and 2 more

Registry-linked trialOpen access · goldAbstract readClinical Trial, Phase IClinical Trial, Phase II
In one paragraph

Trial report in PloS one, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to trial NCT01204502 (Phase I/II Clinical Trial of T-cell Suicide Gene Therapy Following Haploidentical Stem Cell Transplantation), which is not on this map. Cited by 21 papers.

0numbers the graph read from it
0cells of the map it votes in
21citing papers in PubMed
2.8field-weighted citation impact, top 10% 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.

NCT01204502 phase1 / phase2terminatednot on this map

Phase I/II Clinical Trial of T-cell Suicide Gene Therapy Following Haploidentical Stem Cell Transplantation

TypeinterventionalSponsorGreat Ormond Street Hospital for Children NHS Foundation TrustRan2011 to 2013Enrolled2ConditionsHaploidentical Stem Cell TransplantationArmsHSVTK retrovirally-transduced donor T lymphocytes
3 · Its place in the literature

Who cites it

21 citing papers in PubMed, 32 citations in OpenAlex.

  1. Review
  2. Review
  3. Enrichment strategies to enhance genome editing.Journal of biomedical science · 2023
    Review
  4. Article
  5. Spotlight on CYP4B1.International journal of molecular sciences · 2023
    Review
  6. Review
  7. Article
  8. Article
  9. Review
  10. Review
  11. Article
  12. Article
  13. Article
  14. Article
  15. Article
  16. Review
  17. Article
  18. Review
  19. Progress and prospects for engineered T cell therapies.British journal of haematology · 2014
    Review
  20. 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

12 authors at 3 institutions in 2 countries.

Hong ZhanMolecular Immunology Unit, Institute of Child Health (ICH), University College London (UCL), London, United Kingdom.
Kimberly Gilmour
Lucas Chan
Farzin Farzaneh
Anne Marie McNicol
Jin-Hua Xu
Stuart Adams
Boris Fehse
Paul Veys
Adrian Thrasher
Hubert Gaspar
Waseem Qasim
University College London · GBKing's College London · GBUniversität Hamburg · DE

Funding

Biotechnology and Biological Sciences Research Council BB/E005896/1Department of Health
6 · The paper itself

Abstract

unlabelledSuicide gene modified donor T cells can improve immune reconstitution after allogeneic haematopoietic stem cell transplantation (SCT), but can be eliminated in the event of graft versus host disease (GVHD) through the administration of prodrug. Here we report the production and first-in-man use of mismatched donor T cells modified with a gamma-retroviral vector expressing a herpes simplex thymidine kinase (HSVTK):truncated CD34 (tCD34) suicide gene/magnetic selection marker protein. A stable packaging cell line was established to produce clinical grade vector pseudotyped with the Gibbon Ape Leukaemia Virus (GALV). T cells were transduced in a closed bag system following activation with anti-CD3/CD28 beads, and enriched on the basis of CD34 expression. Engineered cells were administered in two escalating doses to three children receiving T-depleted, CD34 stem cell selected, mismatched allogeneic grafts. All patients had pre-existing viral infections and received chemotherapy conditioning without serotherapy. In all three subjects cell therapy was tolerated without acute toxicity or the development of acute GVHD. Circulating gene modified T cells were detectable by flow cytometry and by molecular tracking in all three subjects. There was resolution of virus infections, concordant with detectable antigen-specific T cell responses and gene modified cells persisted for over 12 months. These findings highlight the suitability of tCD34 as a GMP compliant selection marker and demonstrate the feasibility, safety and immunological potential of HSVTK-tCD34 suicide gene modified donor T cells.

trial registrationClinicalTrials.gov NCT01204502 <NCT01204502>

Indexed as

Antigens, CD34ChildChild, PreschoolFemaleFlow CytometryGanciclovirGenes, Transgenic, SuicideGenetic TherapyGenetic VectorsGraft vs Host DiseaseHematopoietic Stem Cell TransplantationHumansInfantInfant, NewbornLeukemia Virus, Gibbon ApeLymphocyte ActivationAntigens, CD34GanciclovirThymidine Kinase

Identifiers

PMID24204746
PMCPMC3804528
OpenAlexW1988754108

What OpenQuestion holds

Textmetadata
LicenceCC BY
Read underepoch 390

Registered trials

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.