Evidence map›Paper›PMID 25080123›Full record

ArticlePloS one2014

Fully human antagonistic antibodies against CCR4 potently inhibit cell signaling and chemotaxis.

Urs B Hagemann, Lavinia Gunnarsson, Solène Géraudie, Ulrike Scheffler, Remko A Griep, Herald Reiersen, Alexander R Duncan, Sergej M Kiprijanov

Open access · goldAbstract read
In one paragraph

Article in PloS one, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 14 papers.

0numbers the graph read from it
0cells of the map it votes in
14citing papers in PubMed
3.2field-weighted citation impact, top 9% 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

14 citing papers in PubMed, 23 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.

Urs B HagemannAffitech Research AS, Oslo, Norway.
Lavinia GunnarssonAffitech Research AS, Oslo, Norway.
Solène GéraudieAffitech Research AS, Oslo, Norway.
Ulrike SchefflerAffitech Research AS, Oslo, Norway.
Remko A GriepAffitech Research AS, Oslo, Norway.
Herald ReiersenAffitech Research AS, Oslo, Norway.
Alexander R DuncanAffitech Research AS, Oslo, Norway.
Sergej M KiprijanovAffitech Research AS, Oslo, Norway.

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

backgroundCC chemokine receptor 4 (CCR4) represents a potentially important target for cancer immunotherapy due to its expression on tumor infiltrating immune cells including regulatory T cells (Tregs) and on tumor cells in several cancer types and its role in metastasis. METHODOLOGY: Using phage display, human antibody library, affinity maturation and a cell-based antibody selection strategy, the antibody variants against human CCR4 were generated. These antibodies effectively competed with ligand binding, were able to block ligand-induced signaling and cell migration, and demonstrated efficient killing of CCR4-positive tumor cells via ADCC and phagocytosis. In a mouse model of human T-cell lymphoma, significant survival benefit was demonstrated for animals treated with the newly selected anti-CCR4 antibodies. SIGNIFICANCE: For the first time, successful generation of anti- G-protein coupled chemokine receptor (GPCR) antibodies using human non-immune library and phage display on GPCR-expressing cells was demonstrated. The generated anti-CCR4 antibodies possess a dual mode of action (inhibition of ligand-induced signaling and antibody-directed tumor cell killing). The data demonstrate that the anti-tumor activity in vivo is mediated, at least in part, through Fc-receptor dependent effector mechanisms, such as ADCC and phagocytosis. Anti-CC chemokine receptor 4 antibodies inhibiting receptor signaling have potential as immunomodulatory antibodies for cancer.

Indexed as

AnimalsAntineoplastic AgentsCalcium SignalingCell Line, TumorCell SurvivalChemokine CCL17ChemotaxisHEK293 CellsHumansInhibitory Concentration 50Macaca mulattaMaleMice, NudePeptide LibraryPlatelet AggregationReceptors, CCR4Antineoplastic AgentsCCR4 protein, humanChemokine CCL17Peptide LibraryReceptors, CCR4Single-Chain Antibodies

Identifiers

PMID25080123
PMCPMC4117600
OpenAlexW2035912733

What OpenQuestion holds

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LicenceCC BY
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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.