Evidence map›Paper›PMID 23211626›Full record

ArticleJournal of immunotherapy (Hagerstown, Md. : 1997)2013

Evaluation of long-term transgene expression in piggyBac-modified human T lymphocytes.

Yozo Nakazawa, Sunandan Saha, Daniel L Galvan, Leslie Huye, Lisa Rollins, Cliona M Rooney, Matthew H Wilson

Open access · greenAbstract read
In one paragraph

Article in Journal of immunotherapy (Hagerstown, Md. : 1997), 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 20 papers.

0numbers the graph read from it
0cells of the map it votes in
20citing papers in PubMed
1.1field-weighted citation impact, top 23% 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

20 citing papers in PubMed, 26 citations in OpenAlex.

  1. Article
  2. Unveiling genomic rearrangements in engineered iPSC lines by optical genome mapping.Molecular therapy. Methods & clinical development · 2025
    Article
  3. Review
  4. Challenges and new technologies in adoptive cell therapy.Journal of hematology & oncology · 2023
    Review
  5. Frontiers in immunology · 2022
    Article
  6. Article
  7. Autologous antigen-presenting cells efficiently expandMolecular therapy. Methods & clinical development · 2021
    Article
  8. Frontiers in immunology · 2021
    Article
  9. Article
  10. PiggyBac-modified CD19-expressing 4T1 cell line for the evaluation of CAR construct.International journal of clinical and experimental pathology · 2019
    Article
  11. Article
  12. Enhanced Expression of Anti-CD19 Chimeric Antigen Receptor inMolecular therapy. Methods & clinical development · 2018
    Article
  13. Article
  14. Article
  15. Article
  16. Article
  17. Article
  18. Article
  19. Article
  20. An adaptable system for improving transposon-based gene expression in vivo via transient transgene repression.FASEB journal : official publication of the Federation of American Societies for Experimental Biology · 2013
    Article
4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

7 authors at 4 institutions in 4 countries.

Yozo NakazawaCenter for Cell and Gene Therapy, Department of Pediatrics, Molecular Virology and Microbiology, Houston, TX, USA.
Sunandan Saha
Daniel L Galvan
Leslie Huye
Lisa Rollins
Cliona M Rooney
Matthew H Wilson
Center for Translational Molecular Medicine · NLGene Therapy Laboratory · FRMichael E. DeBakey VA Medical Center · USPediatrics and Genetics · US

Funding

Tumor BiologyP30CA125123 · NCI · BAYLOR COLLEGE OF MEDICINE · PI DAVID R ROWLEY · 2007 to 2026
$73.9M
Tissue ResourceP50CA126752 · NCI · BAYLOR COLLEGE OF MEDICINE · PI MALCOLM K. BRENNER, HELEN E HESLOP · 2007 to 2026
$51.4M
Novel cell therapy for sustained therapeutic protein delivery in vivoR01DK093660 · NIDDK · VANDERBILT UNIVERSITY MEDICAL CENTER · PI WILSON, MATTHEW H · 2012 to 2022
$3.4M
NCI NIH HHS P30 CA125123NCI NIH HHS P50 CA126752NHLBI NIH HHS 1 U54 HL1081007NIDDK NIH HHS R01 DK093660NIDDK NIH HHS R01DK093660
6 · The paper itself

Abstract

The piggyBac transposon system is a promising nonviral method to genetically modify T cells for immunotherapeutic applications. To evaluate the regulation and stability of transgene expression in human T cells modified with piggyBac-transposons, peripheral blood mononuclear cells were nucleofected with transposase and an enhanced green fluorescence protein (eGFP)-expressing transposon. Single-cell clones that were subsequently stimulated and expanded exhibited homogenous eGFP expression for >26 weeks in culture. CD3 stimulation of the T-cell receptor together with CD28-mediated costimulation resulted in an approximate 10-fold transient increase in eGFP expression, but immunomodulatory cytokines, including interferon-γ, interleukin-12, interleukin-4, and transforming growth factor-β, did not alter transgene expression in actively dividing, activated, or resting T cells. Epigenetic modification with 5-azacytidine or trichostatin-A increased transgene expression indicating that piggyBac-mediated transgene expression could be modulated by methylation or histone acetylation, respectively. We performed transposon copy number analysis of populations of stably transfected T cells, comparing transposon plasmids of 5.6 and 3.5 kb. The smaller vector achieved an average of 22 transposon copies per cell, whereas the larger vector achieved 1.6 copies/cell, implying that transposon copy number can be engineered to be low or high depending on the vector used. Our results provide important insight into the ability of piggyBac to achieve stable genetic modification of T cells for immunotherapy applications and how transgene expression might be regulated by TCR activation, cytokines, and epigenetic mechanisms.

Indexed as

Antineoplastic AgentsAzacitidineCells, CulturedCytokinesDNA Transposable ElementsGene ExpressionGreen Fluorescent ProteinsHistone Deacetylase InhibitorsHumansHydroxamic AcidsLeukocytes, MononuclearNerve Tissue ProteinsReceptors, Antigen, T-CellT-LymphocytesTransfectionTransgenesAntineoplastic AgentsAzacitidineCytokinesDNA Transposable Elementsenhanced green fluorescent proteinGreen Fluorescent ProteinsHistone Deacetylase InhibitorsHydroxamic AcidsNerve Tissue ProteinsPGBD1 protein, humanReceptors, Antigen, T-Celltrichostatin A

Identifiers

PMID23211626
PMCPMC3521868
OpenAlexW1971871284

What OpenQuestion holds

Textmetadata
LicenceTDM
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.