Evidence map›Paper›PMID 26502778›Full record

ArticleMolecular therapy : the journal of the American Society of Gene Therapy2016

Evaluation of TCR Gene Editing Achieved by TALENs, CRISPR/Cas9, and megaTAL Nucleases.

Mark J Osborn, Beau R Webber, Friederike Knipping, Cara-lin Lonetree, Nicole Tennis, Anthony P DeFeo, Amber N McElroy, Colby G Starker, Catherine Lee, Sarah Merkel and 12 more

Registry-linked trialOpen access · bronzeAbstract read
In one paragraph

Article in Molecular therapy : the journal of the American Society of Gene Therapy, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to trial NCT04426669 (A Phase I/II Trial in Patients With Metastatic Gastrointestinal Epithelial Cancer Administering Tumor-Infiltrating Lymphocytes in Which the Gene Encoding CISH Was Inactivated Using the CRISPR/Cas9 System), which is not on this map. Cited by 133 papers.

0numbers the graph read from it
0cells of the map it votes in
133citing papers in PubMed
7.2field-weighted citation impact, top 2% 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.

NCT04426669 phase1 / phase2completednot on this mapstarted 2020, after this paper: background citation

A Phase I/II Trial in Patients With Metastatic Gastrointestinal Epithelial Cancer Administering Tumor-Infiltrating Lymphocytes in Which the Gene Encoding CISH Was Inactivated Using the CRISPR/Cas9 System

TypeinterventionalSponsorIntima Bioscience, Inc.Ran2020 to 2026Enrolled23ConditionsGastrointestinal Epithelial Cancer, Gastrointestinal Neoplasms, Cancer of Gastrointestinal Tract, Cancer, GastrointestinalArmsCyclophosphamide, Fludarabine, Tumor-Infiltrating Lymphocytes (TIL), Aldesleukin
3 · Its place in the literature

Who cites it

133 citing papers in PubMed, 198 citations in OpenAlex.

  1. Article
  2. Review
  3. Strategies to eliminate native T cell receptors for adoptive T cell therapies.Molecular therapy : the journal of the American Society of Gene Therapy · 2026
    Review
  4. Review
  5. Review
  6. Article
  7. Review
  8. Review
  9. Article
  10. Review
  11. Review
  12. Article
  13. Review
  14. Article
  15. Review
  16. Practical immunomodulatory landscape of glioblastoma multiforme (GBM) therapy.Journal of the Egyptian National Cancer Institute · 2024
    Review
  17. Review
  18. Review
  19. Article
  20. Synthetic Gene Circuits for Regulation of Next-Generation Cell-Based Therapeutics.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2024
    Review

73 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

22 authors at 6 institutions in 2 countries.

Mark J OsbornDepartment of Pediatrics, Division of Blood and Marrow Transplantation, University of Minnesota, Minneapolis, Minnesota, USA.
Beau R WebberDepartment of Pediatrics, Division of Blood and Marrow Transplantation, University of Minnesota, Minneapolis, Minnesota, USA.
Friederike KnippingGerman Cancer Research Center (DKFZ), Heidelberg, Germany.
Cara-lin LonetreeDepartment of Pediatrics, Division of Blood and Marrow Transplantation, University of Minnesota, Minneapolis, Minnesota, USA.
Nicole TennisDepartment of Pediatrics, Division of Blood and Marrow Transplantation, University of Minnesota, Minneapolis, Minnesota, USA.
Anthony P DeFeoDepartment of Pediatrics, Division of Blood and Marrow Transplantation, University of Minnesota, Minneapolis, Minnesota, USA.
Amber N McElroyDepartment of Pediatrics, Division of Blood and Marrow Transplantation, University of Minnesota, Minneapolis, Minnesota, USA.
Colby G StarkerCenter for Genome Engineering, University of Minnesota, Minneapolis, Minnesota, USA.
Catherine LeeDepartment of Pediatrics, Division of Blood and Marrow Transplantation, University of Minnesota, Minneapolis, Minnesota, USA.
Sarah MerkelDepartment of Pediatrics, Division of Blood and Marrow Transplantation, University of Minnesota, Minneapolis, Minnesota, USA.
Troy C LundDepartment of Pediatrics, Division of Blood and Marrow Transplantation, University of Minnesota, Minneapolis, Minnesota, USA.
Karen S Kelly-SprattBen Towne Center for Childhood Cancer Research, Seattle Children's Research Institute, Seattle, Washington, USA.
Michael C JensenBen Towne Center for Childhood Cancer Research, Seattle Children's Research Institute, Seattle, Washington, USA.
Daniel F VoytasCenter for Genome Engineering, University of Minnesota, Minneapolis, Minnesota, USA.
Christof von KalleGerman Cancer Research Center (DKFZ), Heidelberg, Germany.
Manfred SchmidtGerman Cancer Research Center (DKFZ), Heidelberg, Germany.
Richard GabrielGerman Cancer Research Center (DKFZ), Heidelberg, Germany.
Keli L HippenDepartment of Pediatrics, Division of Blood and Marrow Transplantation, University of Minnesota, Minneapolis, Minnesota, USA.
Jeffrey S MillerDepartment of Medicine, University of Minnesota, Minneapolis, Minnesota, USA.
Andrew M ScharenbergSeattle Children's Research Institute, and University of Washington School of Medicine, Seattle, Washington, USA.
Jakub TolarDepartment of Pediatrics, Division of Blood and Marrow Transplantation, University of Minnesota, Minneapolis, Minnesota, USA.
Bruce R BlazarDepartment of Pediatrics, Division of Blood and Marrow Transplantation, University of Minnesota, Minneapolis, Minnesota, USA.
University of Minnesota · USSeattle Children's Hospital · USGerman Cancer Research Center · DEHeidelberg University · DENational Center for Tumor Diseases · DEUniversity of Washington · US

Funding

Women's CancerP30CA077598 · NCI · UNIVERSITY OF MINNESOTA TWIN CITIES · PI Douglas Yee · 1998 to 2026
$100.4M
Trial Design and Biostatistical Support CoreP01CA065493 · NCI · UNIVERSITY OF MINNESOTA TWIN CITIES · PI Mark J Osborn · 1995 to 2026
$48.2M
University of Minnesota Clinical and Translational Science Institute (UMN CTSI)UL1TR000114 · NCATS · UNIVERSITY OF MINNESOTA · PI BLAZAR, BRUCE R · 2012 to 2015
$35.0M
TRAINING IN HEMOGLOBIN &CELL MEMBRANE RESEARCHT32HL007062 · NHLBI · UNIVERSITY OF MINNESOTA TWIN CITIES · PI Jeffrey S. Miller, Gregory M Vercellotti · 1985 to 2026
$10.3M
GVL TO REDUCE AML RELAPSE AFTER MURINE ALLOGENEIC BMTR01CA072669 · NCI · UNIVERSITY OF MINNESOTA TWIN CITIES · PI BLAZAR, BRUCE R · 1997 to 2017
$4.9M
Skin-targeted Cell Therapy for Recessive Dystrophic Epidermolysis BullosaR01AR063070 · NIAMS · UNIVERSITY OF MINNESOTA · PI Mark J Osborn, Jakub Tolar · 2013 to 2026
$4.5M
Stem Cell Biology Training ProgramT32GM113846 · NIGMS · UNIVERSITY OF MINNESOTA · PI PERLINGEIRO, RITA C. R. · 2015 to 2019
$712k
NCATS NIH HHS 8UL1TR000114-02NCATS NIH HHS UL1 TR000114NCATS NIH HHS UL1TR000114NCI NIH HHS P01 CA065493NCI NIH HHS P30 CA077598NCI NIH HHS R01 CA072669NHLBI NIH HHS T32 HL007062NHLBI NIH HHS T32-HL007062NIAMS NIH HHS R01 AR063070NIGMS NIH HHS T32 GM113846
6 · The paper itself

Abstract

Present adoptive immunotherapy strategies are based on the re-targeting of autologous T-cells to recognize tumor antigens. As T-cell properties may vary significantly between patients, this approach can result in significant variability in cell potency that may affect therapeutic outcome. More consistent results could be achieved by generating allogeneic cells from healthy donors. An impediment to such an approach is the endogenous T-cell receptors present on T-cells, which have the potential to direct dangerous off-tumor antihost reactivity. To address these limitations, we assessed the ability of three different TCR-α-targeted nucleases to disrupt T-cell receptor expression in primary human T-cells. We optimized the conditions for the delivery of each reagent and assessed off-target cleavage. The megaTAL and CRISPR/Cas9 reagents exhibited the highest disruption efficiency combined with low levels of toxicity and off-target cleavage, and we used them for a translatable manufacturing process to produce safe cellular substrates for next-generation immunotherapies.

Indexed as

CRISPR-Cas SystemsEndonucleasesGene EditingTranscription Activator-Like Effector NucleasesBinding SitesCell Culture TechniquesCell LineGene TargetingGenetic LociGene Transfer TechniquesGenomeHumansImmunophenotypingNeoplasmsPhenotypeProtein BindingEndonucleasesReceptors, Antigen, T-CellRecombinant Fusion ProteinsTranscription Activator-Like Effector Nucleases

Identifiers

PMID26502778
PMCPMC4786913
OpenAlexW2247762492

What OpenQuestion holds

Textmetadata
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.