Evidence map›Paper›PMID 25427612›Full record

ArticleGene therapy2015

The Tol2 transposon system mediates the genetic engineering of T-cells with CD19-specific chimeric antigen receptors for B-cell malignancies.

T Tsukahara, N Iwase, K Kawakami, M Iwasaki, C Yamamoto, K Ohmine, R Uchibori, T Teruya, H Ido, Y Saga and 6 more

Open access · greenAbstract read
In one paragraph

Article in Gene therapy, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 22 papers.

0numbers the graph read from it
0cells of the map it votes in
22citing papers in PubMed
1.5field-weighted citation impact, top 17% 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

22 citing papers in PubMed, 32 citations in OpenAlex.

  1. Article
  2. Review
  3. Current Non-Viral-Based Strategies to Manufacture CAR-T Cells.International journal of molecular sciences · 2024
    Review
  4. Article
  5. Article
  6. Article
  7. Article
  8. Review
  9. Review
  10. Characterizing piggyBat-a transposase for genetic modification of T cells.Molecular therapy. Methods & clinical development · 2022
    Article
  11. Review
  12. CAR T-Cell Production Using Nonviral Approaches.Journal of immunology research · 2021
    Review
  13. Article
  14. Review
  15. Review
  16. Review
  17. Review
  18. Article
  19. Article
  20. Review
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

16 authors at 5 institutions in 2 countries.

T Tsukahara1] Division of Genetic Therapeutics, Center for Molecular Medicine, Jichi Medical University, Shimotsuke, Tochigi, Japan [2] Division of Immuno-Gene and Cell Therapy (Takara Bio), Jichi Medical University, Shimotsuke, Tochigi, Japan.
N IwaseDivision of Genetic Therapeutics, Center for Molecular Medicine, Jichi Medical University, Shimotsuke, Tochigi, Japan.
K KawakamiDivision of Molecular and Developmental Biology, National Institute of Genetics, Mishima, Shizuoka, Japan.
M IwasakiDivision of Molecular and Developmental Biology, National Institute of Genetics, Mishima, Shizuoka, Japan.
C Yamamoto1] Division of Genetic Therapeutics, Center for Molecular Medicine, Jichi Medical University, Shimotsuke, Tochigi, Japan [2] Division of Hematology, Department of Medicine, Jichi Medical University, Shimotsuke, Tochigi, Japan.
K Ohmine1] Division of Immuno-Gene and Cell Therapy (Takara Bio), Jichi Medical University, Shimotsuke, Tochigi, Japan [2] Division of Hematology, Department of Medicine, Jichi Medical University, Shimotsuke, Tochigi, Japan.
R Uchibori1] Division of Genetic Therapeutics, Center for Molecular Medicine, Jichi Medical University, Shimotsuke, Tochigi, Japan [2] Division of Immuno-Gene and Cell Therapy (Takara Bio), Jichi Medical University, Shimotsuke, Tochigi, Japan.
T TeruyaDivision of Immuno-Gene and Cell Therapy (Takara Bio), Jichi Medical University, Shimotsuke, Tochigi, Japan.
H IdoDivision of Immuno-Gene and Cell Therapy (Takara Bio), Jichi Medical University, Shimotsuke, Tochigi, Japan.
Y Saga1] Division of Genetic Therapeutics, Center for Molecular Medicine, Jichi Medical University, Shimotsuke, Tochigi, Japan [2] Department of Obstetrics and Gynecology, Jichi Medical University, Shimotsuke, Tochigi, Japan.
M UrabeDivision of Genetic Therapeutics, Center for Molecular Medicine, Jichi Medical University, Shimotsuke, Tochigi, Japan.
H MizukamiDivision of Genetic Therapeutics, Center for Molecular Medicine, Jichi Medical University, Shimotsuke, Tochigi, Japan.
A KumeDivision of Genetic Therapeutics, Center for Molecular Medicine, Jichi Medical University, Shimotsuke, Tochigi, Japan.
M NakamuraHuman Gene Sciences Center, Tokyo Medical and Dental University, Bunkyo-ku, Tokyo, Japan.
R BrentjensDepartment of Medicine, Memorial Sloan Kettering Cancer Center, New York, NY, USA.
K Ozawa1] Division of Genetic Therapeutics, Center for Molecular Medicine, Jichi Medical University, Shimotsuke, Tochigi, Japan [2] Division of Immuno-Gene and Cell Therapy (Takara Bio), Jichi Medical University, Shimotsuke, Tochigi, Japan [3] Division of Hematology, Department of Medicine, Jichi Medical University, Shimotsuke, Tochigi, Japan.
Jichi Medical University · JPTakara (Japan) · JPNational Institute of Genetics · JPMemorial Sloan Kettering Cancer Center · USTokyo Medical and Dental University · JP

Funding

X-RAY CRYSTALLOGRAPHYP30CA008748 · NCI · SLOAN-KETTERING INSTITUTE FOR CANCER RES · PI Nicholas D Socci · 1985 to 2026
$347.4M
NCI NIH HHS P30 CA008748
6 · The paper itself

Abstract

Engineered T-cell therapy using a CD19-specific chimeric antigen receptor (CD19-CAR) is a promising strategy for the treatment of advanced B-cell malignancies. Gene transfer of CARs to T-cells has widely relied on retroviral vectors, but transposon-based gene transfer has recently emerged as a suitable nonviral method to mediate stable transgene expression. The advantages of transposon vectors compared with viral vectors include their simplicity and cost-effectiveness. We used the Tol2 transposon system to stably transfer CD19-CAR into human T-cells. Normal human peripheral blood lymphocytes were co-nucleofected with the Tol2 transposon donor plasmid carrying CD19-CAR and the transposase expression plasmid and were selectively propagated on NIH3T3 cells expressing human CD19. Expanded CD3(+) T-cells with stable and high-level transgene expression (~95%) produced interferon-γ upon stimulation with CD19 and specifically lysed Raji cells, a CD19(+) human B-cell lymphoma cell line. Adoptive transfer of these T-cells suppressed tumor progression in Raji tumor-bearing Rag2(-/-)γc(-/-) immunodeficient mice compared with control mice. These results demonstrate that the Tol2 transposon system could be used to express CD19-CAR in genetically engineered T-cells for the treatment of refractory B-cell malignancies.

Indexed as

DNA Transposable ElementsAnimalsAntigens, CD19Cell Line, TumorCoculture TechniquesGenetic EngineeringGenetic TherapyHumansImmunotherapy, AdoptiveLymphoma, B-CellMiceMice, Inbred BALB CMice, KnockoutMolecular Sequence DataNeoplasm TransplantationNIH 3T3 CellsAntigens, CD19DNA Transposable ElementsReceptors, Antigen, T-CellRecombinant Fusion Proteins

Identifiers

PMID25427612
PMCPMC5548386
OpenAlexW2050002181

What OpenQuestion holds

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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.