Evidence map›Paper›PMID 19171765›Full record

ArticleThe Journal of experimental medicine2009

Increasing functional avidity of TCR-redirected T cells by removing defined N-glycosylation sites in the TCR constant domain.

Jürgen Kuball, Beate Hauptrock, Victoria Malina, Edite Antunes, Ralf-Holger Voss, Matthias Wolfl, Roland Strong, Matthias Theobald, Philip D Greenberg

Abstract read
In one paragraph

Article in The Journal of experimental medicine, 2009. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 80 papers.

0numbers the graph read from it
0cells of the map it votes in
80citing papers in PubMed
–field-weighted citation impact
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

80 citing papers in PubMed.

  1. Article
  2. Article
  3. Review
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  6. Article
  7. Review
  8. Food for thought: Nutrient metabolism controlling early T cell development.BioEssays : news and reviews in molecular, cellular and developmental biology · 2025
    Review
  9. Review
  10. Focusing on CD8Journal of experimental & clinical cancer research : CR · 2024
    Review
  11. Article
  12. Article
  13. Review
  14. Hyper α2,6-Sialylation Promotes CD4Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2023
    Article
  15. Article
  16. Review
  17. Review
  18. Article
  19. Article
  20. Review

20 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.

Jürgen KuballProgram in Immunology, Fred Hutchinson Cancer Research Center, Seattle, WA 98109, USA. j.h.e.kuball@umcutrecht.nl
Beate Hauptrock
Victoria Malina
Edite Antunes
Ralf-Holger Voss
Matthias Wolfl
Roland Strong
Matthias Theobald
Philip D Greenberg

Funding

VIRUS-MEDIATED MYELOSUPPRESSIONP01CA018029 · NCI · FRED HUTCHINSON CANCER RESEARCH CENTER · PI Geoffrey Roger HILL · 1985 to 2026
$128.4M
MECHANISMS OF MURINE TUMOR ERADICATION BY IMMUNOTHERAPYR37CA033084 · NCI · UNIVERSITY OF WASHINGTON · PI GREENBERG, PHILIP D · 1991 to 2006
$3.5M
NCI NIH HHS P01 CA018029NCI NIH HHS P01 CA18029NCI NIH HHS R37 CA033084NCI NIH HHS R37 CA33084
6 · The paper itself

Abstract

Adoptive transfer of T lymphocytes transduced with a T cell receptor (TCR) to impart tumor reactivity has been reported as a potential strategy to redirect immune responses to target cancer cells (Schumacher, T.N. 2002. Nat. Rev. Immunol. 2:512-519). However, the affinity of most TCRs specific for shared tumor antigens that can be isolated is usually low. Thus, strategies to increase the affinity of TCRs or the functional avidity of TCR-transduced T cells might be therapeutically beneficial. Because glycosylation affects the flexibility, movement, and interactions of surface molecules, we tested if selectively removing conserved N-glycoslyation sites in the constant regions of TCR alpha or beta chains could increase the functional avidity of T cells transduced with such modified TCRs. We observed enhanced functional avidity and improved recognition of tumor cells by T cells harboring TCR chains with reduced N-glycosylation (DeltaTCR) as compared with T cells with wild-type (WT) TCR chains. T cells transduced with WT or DeltaTCR chains bound tetramer equivalently at 4 degrees C, but tetramer binding was enhanced at 37 degrees C, predominantly as a result of reduced tetramer dissociation. This suggested a temperature-dependent mechanism such as TCR movement in the cell surface or structural changes of the TCR allowing improved multimerization. This strategy was effective with mouse and human TCRs specific for different antigens and, thus, should be readily translated to TCRs with any specificity.

Indexed as

Models, MolecularAdoptive TransferAnimalsCD4-Positive T-LymphocytesCell Line, TumorEnzyme-Linked Immunosorbent AssayFlow CytometryGlycosylationHumansMiceNeoplasmsProtein BindingReceptors, Antigen, T-CellReverse Transcriptase Polymerase Chain ReactionTemperatureReceptors, Antigen, T-Cell

Identifiers

PMID19171765
PMCPMC2646573

What OpenQuestion holds

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LicenceCC BY-NC-SA
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.