Evidence map›Paper›PMID 29122757›Full record

ArticleBlood2018

CRISPR-mediated TCR replacement generates superior anticancer transgenic T cells.

Mateusz Legut, Garry Dolton, Afsar Ali Mian, Oliver G Ottmann, Andrew K Sewell

Open access · bronzeAbstract read
In one paragraph

Article in Blood, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 146 papers.

0numbers the graph read from it
0cells of the map it votes in
146citing papers in PubMed
9.3field-weighted citation impact, top 1% 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

146 citing papers in PubMed, 218 citations in OpenAlex.

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  9. Autologous profiling reveals inter-patient heterogeneity in Vδ2Journal for immunotherapy of cancer · 2025
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  16. Application of adoptive cell therapy in malignant melanoma.Journal of translational medicine · 2025
    Review
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86 more citing papers are in PubMed but not listed here.

4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

5 authors at 2 institutions in 2 countries.

Mateusz LegutDivision of Infection and Immunity, School of Medicine.
Garry DoltonDivision of Infection and Immunity, School of Medicine.
Afsar Ali MianHaematology, Division of Cancer and Genetics, School of Medicine, Cardiff University, Cardiff, United Kingdom.
Oliver G OttmannHaematology, Division of Cancer and Genetics, School of Medicine, Cardiff University, Cardiff, United Kingdom.ORCID 0000-0001-9559-1330
Andrew K SewellDivision of Infection and Immunity, School of Medicine.ORCID 0000-0003-3194-3135
Institute of Infection and Immunity · CACardiff University · GB

Funding

Cancer Research UKWellcome TrustWellcome Trust WT100327MA
6 · The paper itself

Abstract

Adoptive transfer of T cells genetically modified to express a cancer-specific T-cell receptor (TCR) has shown significant therapeutic potential for both hematological and solid tumors. However, a major issue of transducing T cells with a transgenic TCR is the preexisting expression of TCRs in the recipient cells. These endogenous TCRs compete with the transgenic TCR for surface expression and allow mixed dimer formation. Mixed dimers, formed by mispairing between the endogenous and transgenic TCRs, may harbor autoreactive specificities. To circumvent these problems, we designed a system where the endogenous TCR-β is knocked out from the recipient cells using clustered regularly interspaced short palindromic repeats (CRISPR)/CRISPR-associated protein-9 (Cas9) technology, simultaneously with transduction with a cancer-reactive receptor of choice. This TCR replacement strategy resulted in markedly increased surface expression of transgenic αβ and γδ TCRs, which in turn translated to a stronger, and more polyfunctional, response of engineered T cells to their target cancer cell lines. Additionally, the TCR-plus-CRISPR-modified T cells were up to a thousandfold more sensitive to antigen than standard TCR-transduced T cells or conventional model proxy systems used for studying TCR activity. Finally, transduction with a pan-cancer-reactive γδ TCR used in conjunction with CRISPR/Cas9 knockout of the endogenous αβ TCR resulted in more efficient redirection of CD4

Indexed as

TransgenesAntineoplastic AgentsCell Line, TumorCRISPR-Associated Protein 9CRISPR-Cas SystemsGene Knockout TechniquesGenes, T-Cell ReceptorHEK293 CellsHematologic NeoplasmsHumansReceptors, Antigen, T-Cell, gamma-deltaReproducibility of ResultsT-LymphocytesAntineoplastic AgentsCRISPR-Associated Protein 9Receptors, Antigen, T-Cell, gamma-delta

Identifiers

PMID29122757
PMCPMC5774207
OpenAlexW2767574526

What OpenQuestion holds

Textmetadata
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.