Evidence map›Paper›PMID 19752751›Full record

ArticleJournal of immunotherapy (Hagerstown, Md. : 1997)2009

Optimization of the PiggyBac transposon system for the sustained genetic modification of human T lymphocytes.

Yozo Nakazawa, Leslie E Huye, Gianpietro Dotti, Aaron E Foster, Juan F Vera, Pallavi R Manuri, Carl H June, Cliona M Rooney, Matthew H Wilson

Open access · greenAbstract read
In one paragraph

Article in Journal of immunotherapy (Hagerstown, Md. : 1997), 2009. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 78 papers.

0numbers the graph read from it
0cells of the map it votes in
78citing papers in PubMed
4.3field-weighted citation impact, top 5% 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

78 citing papers in PubMed, 110 citations in OpenAlex.

  1. Article
  2. Article
  3. Article
  4. Article
  5. Optimizing CAR-T treatment: A TMolecular therapy : the journal of the American Society of Gene Therapy · 2025
    Review
  6. Spatial Control of CAR T Cell Activation Using Tumor-Homing Polymers.Journal of the American Chemical Society · 2025
    Article
  7. Article
  8. Targeted gene delivery systems for T-cell engineering.Cellular oncology (Dordrecht, Netherlands) · 2024
    Review
  9. Review
  10. Article
  11. Review
  12. Article
  13. Article
  14. Article
  15. Review
  16. Frontiers in immunology · 2022
    Article
  17. Review
  18. Review
  19. Article
  20. piggyBac system to co-express NKG2D CAR and IL-15 to augment theMolecular therapy. Methods & clinical development · 2021
    Article

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

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

9 authors at 5 institutions in 1 country.

Yozo NakazawaCenter for Cell and Gene Therapy, Baylor College of Medicine, Houston, TX 77030, USA.
Leslie E Huye
Gianpietro Dotti
Aaron E Foster
Juan F Vera
Pallavi R Manuri
Carl H June
Cliona M Rooney
Matthew H Wilson
Pediatrics and Genetics · USBaylor College of Medicine · USMichael E. DeBakey VA Medical Center · USPhiladelphia University · USThe University of Texas MD Anderson Cancer Center · US

Funding

Tissue ResourceP50CA126752 · NCI · BAYLOR COLLEGE OF MEDICINE · PI MALCOLM K. BRENNER, HELEN E HESLOP · 2007 to 2026
$51.4M
Validation of Suicide Strategies for Cellular TherapyU54HL081007 · NHLBI · BAYLOR COLLEGE OF MEDICINE · PI BRENNER, MALCOLM K. · 2005 to 2009
$10.2M
Culture systems to propogate human T cell subsetsR01CA105216 · NCI · UNIVERSITY OF PENNSYLVANIA · PI JUNE, CARL H. · 2004 to 2008
$1.5M
NCI NIH HHS P50 CA126752NCI NIH HHS R01 CA105216NHLBI NIH HHS 1 U54 HL1081007NHLBI NIH HHS U54 HL081007
6 · The paper itself

Abstract

Optimal implementation of adoptive T-cell therapy for cancer will likely require multiple and maintained genetic modifications of the infused T cells and their progeny so that they home to tumor sites and recognize tumor cells, overcome tumor immune evasion strategies, and remain safe. Retroviral vectors readily transduce T cells and integrate into the host cell genome, but have a limited capacity for multigene insertion and cotransduction and are prohibitively expensive to produce at clinical grade. Genetic modification of T cells using transposons as integrating plasmids is an attractive alternative because of the increased simplicity and cost of production. Of available transposons, piggyBac has the higher transposase activity and larger cargo capacity, and we now evaluate piggyBac for potential adoptive therapies with primary T cells. PiggyBac transposons mediated stable gene expression in approximately 20% of primary T cells without selection. Treatment and maintenance of T cells with interleukin-15 increased stable transgene expression up to approximately 40% and expression was sustained through multiple logs of expansion for over 9 weeks in culture. We demonstrate simultaneous integration of 2 independent transposons in 20% of T cells, a frequency that could be increased to over 85% by selection of a transgenic surface marker (truncated CD19). PiggyBac could also deliver transposons of up to 13 kb with 10,000-fold expansion of transduced T cells in culture and finally we demonstrate delivery of a functional suicide gene (iCasp9). PiggyBac transposons may thus be used to express the multiple integrated transgenes that will likely be necessary for the broader success of T-cell therapy.

Indexed as

Genetic VectorsImmunotherapy, AdoptiveApoptosisCancer VaccinesCaspase 9Cells, CulturedDNA Transposable ElementsGenetic EngineeringHumansInterleukin-15T-LymphocytesTransgenesCancer VaccinesCASP9 protein, humanCaspase 9DNA Transposable ElementsInterleukin-15

Identifiers

PMID19752751
PMCPMC2796278
OpenAlexW2028984998

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.