Evidence map›Paper›PMID 22526592›Full record

ArticleJournal of clinical immunology2012

Dual targeting of ErbB2 and MUC1 in breast cancer using chimeric antigen receptors engineered to provide complementary signaling.

Scott Wilkie, May C I van Schalkwyk, Steve Hobbs, David M Davies, Sjoukje J C van der Stegen, Ana C Parente Pereira, Sophie E Burbridge, Carol Box, Suzanne A Eccles, John Maher

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In one paragraph

Article in Journal of clinical immunology, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 306 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
306citing papers in PubMed, 1 pooled it
7.0field-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.

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

306 citing papers in PubMed, 1 synthesis or guideline pooled it, 481 citations in OpenAlex.

  1. Mapping the clinical landscape of multifunctional CAR T cells: Targets, trends, and synergies.Molecular therapy : the journal of the American Society of Gene Therapy · 2026
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  20. Engineering resilient CAR T cells for immunosuppressive environment.Molecular therapy : the journal of the American Society of Gene Therapy · 2025
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246 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

10 authors at 5 institutions in 1 country.

Scott WilkieKing's College London, King's Health Partners Integrated Cancer Center, Department of Research Oncology, Guy's Hospital Campus, Great Maze Pond, London, SE1 9RT, UK.
May C I van Schalkwyk
Steve Hobbs
David M Davies
Sjoukje J C van der Stegen
Ana C Parente Pereira
Sophie E Burbridge
Carol Box
Suzanne A Eccles
John Maher
King's College London · GBCancer Research UK · GBGuy's Hospital · GBKings Health Partners · GBInstitute of Cancer Research · GB

Funding

Breast Cancer Now 2006NOVPR18Cancer Research UK 11566Cancer Research UK CA309/A8274Prostate Cancer UK PA12-06
6 · The paper itself

Abstract

purposeChimeric antigen receptor (CAR) engineered T-cells occupy an increasing niche in cancer immunotherapy. In this context, CAR-mediated CD3ζ signaling is sufficient to elicit cytotoxicity and interferon-γ production while the additional provision of CD28-mediated signal 2 promotes T-cell proliferation and interleukin (IL)-2 production. This compartmentalisation of signaling opens the possibility that complementary CARs could be used to focus T-cell activation within the tumor microenvironment.

methodsHere, we have tested this principle by co-expressing an ErbB2- and MUC1-specific CAR that signal using CD3ζ and CD28 respectively. Stoichiometric co-expression of transgenes was achieved using the SFG retroviral vector containing an intervening Thosea asigna peptide.

resultsWe found that "dual-targeted" T-cells kill ErbB2(+) tumor cells efficiently and proliferate in a manner that requires co-expression of MUC1 and ErbB2 by target cells. Notably, however, IL-2 production was modest when compared to control CAR-engineered T-cells in which signaling is delivered by a fused CD28 + CD3ζ endodomain.

conclusionsThese findings demonstrate the principle that dual targeting may be achieved using genetically targeted T-cells and pave the way for testing of this strategy in vivo.

Indexed as

Immunotherapy, AdoptiveAdaptor Proteins, Signal TransducingBreast NeoplasmsCell Line, TumorCell ProliferationCells, CulturedFemaleHumansInterferon-gammaInterleukin-2Mucin-1Receptors, Antigen, T-CellSignal TransductionT-LymphocytesAdaptor Proteins, Signal TransducingERBIN protein, humanInterferon-gammaInterleukin-2MUC1 protein, humanMucin-1Receptors, Antigen, T-Cell

Identifiers

PMID22526592
OpenAlexW1965411082

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.