Evidence map›Paper›PMID 27314237›Full record

ArticlePloS one2016

Combination of NK Cells and Cetuximab to Enhance Anti-Tumor Responses in RAS Mutant Metastatic Colorectal Cancer.

John Pradeep Veluchamy, Jan Spanholtz, Marleen Tordoir, Victor L Thijssen, Daniëlle A M Heideman, Henk M W Verheul, Tanja D de Gruijl, Hans J van der Vliet

Open access · goldAbstract read
In one paragraph

Article in PloS one, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 50 papers.

0numbers the graph read from it
0cells of the map it votes in
50citing papers in PubMed
5.3field-weighted citation impact, top 4% 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

50 citing papers in PubMed, 84 citations in OpenAlex.

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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

8 authors at 2 institutions in 1 country.

John Pradeep VeluchamyDepartment of Medical Oncology, VU University Medical Center, Cancer Center Amsterdam, Amsterdam, The Netherlands.ORCID http://orcid.org/0000-0002-5681-1860
Jan SpanholtzGlycostem Therapeutics, Oss, The Netherlands.
Marleen TordoirGlycostem Therapeutics, Oss, The Netherlands.
Victor L ThijssenDepartment of Medical Oncology, VU University Medical Center, Cancer Center Amsterdam, Amsterdam, The Netherlands.
Daniëlle A M HeidemanDepartment of Pathology, VU University Medical Center, Amsterdam, The Netherlands.
Henk M W VerheulDepartment of Medical Oncology, VU University Medical Center, Cancer Center Amsterdam, Amsterdam, The Netherlands.
Tanja D de GruijlDepartment of Medical Oncology, VU University Medical Center, Cancer Center Amsterdam, Amsterdam, The Netherlands.
Hans J van der VlietDepartment of Medical Oncology, VU University Medical Center, Cancer Center Amsterdam, Amsterdam, The Netherlands.
Cancer Center Amsterdam · NLAmsterdam UMC Location Vrije Universiteit Amsterdam · NL

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

The ability of Natural Killer (NK) cells to kill tumor targets has been extensively studied in various hematological malignancies. However, NK cell therapy directed against solid tumors is still in early development. Epidermal Growth Factor Receptor (EGFR) targeted therapies using monoclonal antibodies (mAbs) such as cetuximab and panitumumab are widely used for the treatment of metastatic colorectal cancer (mCRC). Still, the clinical efficacy of this treatment is hampered by mutations in RAS gene, allowing tumors to escape from anti-EGFR mAb therapy. It is well established that NK cells kill tumor cells by natural cytotoxicity and can in addition be activated upon binding of IgG1 mAbs through Fc receptors (CD16/FcγRIIIa) on their surface, thereby mediating antibody dependent cellular cytotoxicity (ADCC). In the current study, activated Peripheral Blood NK cells (PBNK) were combined with anti-EGFR mAbs to study their effect on the killing of EGFR+/- cancer cell lines, including those with RAS mutations. In vitro cytotoxicity experiments using colon cancer primary tumors and cell lines COLO320, Caco-2, SW620, SW480 and HT-29, demonstrated that PBNK cells are cytotoxic for a range of tumor cells, regardless of EGFR, RAS or BRAF status and at low E:T ratios. Cetuximab enhanced the cytotoxic activity of NK cells on EGFR+ tumor cells (either RASwt, RASmut or BRAFmut) in a CD16 dependent manner, whereas it could not increase the killing of EGFR- COLO320. Our study provides a rationale to strengthen NK cell immunotherapy through a combination with cetuximab for RAS and BRAF mutant mCRC patients.

Indexed as

Killer Cells, NaturalAntibodies, Monoclonal, HumanizedCaco-2 CellsCell- and Tissue-Based TherapyCell ProliferationCetuximabColorectal NeoplasmsErbB ReceptorsHT29 CellsHumansImmunoglobulin GMutationNeoplasm MetastasisProto-Oncogene Proteins B-rafras ProteinsAntibodies, Monoclonal, HumanizedBRAF protein, humanCetuximabEGFR protein, humanErbB ReceptorsImmunoglobulin GProto-Oncogene Proteins B-rafras Proteins

Identifiers

PMID27314237
PMCPMC4912059
OpenAlexW2438839873

What OpenQuestion holds

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Registered trials

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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.