Evidence map›Paper›PMID 23977237›Full record

ArticlePloS one2013

Antagonistic TNF receptor one-specific antibody (ATROSAB): receptor binding and in vitro bioactivity.

Fabian Richter, Timo Liebig, Eric Guenzi, Andreas Herrmann, Peter Scheurich, Klaus Pfizenmaier, Roland E Kontermann

Open access · goldAbstract read
In one paragraph

Article in PloS one, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 26 papers.

0numbers the graph read from it
0cells of the map it votes in
26citing papers in PubMed
2.8field-weighted citation impact, top 10% 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

26 citing papers in PubMed, 41 citations in OpenAlex.

  1. Review
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  11. Selective Targeting of TNF Receptors as a Novel Therapeutic Approach.Frontiers in cell and developmental biology · 2020
    Review
  12. Article
  13. Article
  14. Article
  15. Article
  16. A New Venue of TNF Targeting.International journal of molecular sciences · 2018
    Review
  17. Review
  18. Review
  19. Article
  20. Essential protective role of tumor necrosis factor receptor 2 in neurodegeneration.Proceedings of the National Academy of Sciences of the United States of America · 2016
    Article
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

7 authors at 1 institution in 1 country.

Fabian RichterInstitut für Zellbiologie und Immunologie, Universität Stuttgart, Stuttgart, Germany.
Timo Liebig
Eric Guenzi
Andreas Herrmann
Peter Scheurich
Klaus Pfizenmaier
Roland E Kontermann
University of Stuttgart · DE

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

backgroundSelective inhibition of TNFR1 signaling holds the potential to greatly reduce the pro-inflammatory activity of TNF, while leaving TNFR2 untouched, thus allowing for cell survival and tissue homeostasis. ATROSAB is a humanized antagonistic anti-TNFR1 antibody developed for the treatment of inflammatory diseases. METHODOLOGY/PRINCIPAL

findingsThe epitope of ATROSAB resides in the N-terminal region of TNFR1 covering parts of CRD1 and CRD2. By site-directed mutagenesis, we identified Arg68 and His69 of TNFR1 as important residues for ATROSAB binding. ATROSAB inhibited binding of (125)I-labeled TNF to HT1080 in the subnanomolar range. Furthermore, ATROSAB inhibited release of IL-6 and IL-8 from HeLa and HT1080 cells, respectively, induced by TNF or lymphotoxin alpha (LTα). Different from an agonistic antibody (Htr-9), which binds to a region close to the ATROSAB epitope but elicits strong TNFR1 activation, ATROSAB showed a negligible induction of IL-6 and IL-8 production over a broad concentration range. We further verified that ATROSAB, comprising mutations within the Fc region known to abrogate complement fixation and antibody-mediated cellular effector functions, indeed lacks binding activity for C1q, FcγRI (CD64), FcγRIIB (CD32b), and FcγRIII (CD16) disabling ADCC and CDC. CONCLUSIONS/SIGNIFICANCE: The data corroborate ATROSAB's unique function as a TNFR1-selective antagonist efficiently blocking both TNF and LTα action. In agreement with recent studies of TNFR1 complex formation and activation, we suggest a model of the underlying mechanism of TNFR1 inhibition by ATROSAB.

Indexed as

Amino Acid SequenceAnimalsAntibodies, Monoclonal, HumanizedCell Line, TumorComplement C1qGene Expression RegulationHumansInterleukin-6Interleukin-6 InhibitorsInterleukin-8KineticsLymphotoxin-alphaMiceModels, MolecularMolecular Sequence DataProtein BindingAntibodies, Monoclonal, HumanizedComplement C1qIL6 protein, humanInterleukin-6Interleukin-6 InhibitorsInterleukin-8Lymphotoxin-alphaReceptors, IgGReceptors, Tumor Necrosis Factor, Type ITumor Necrosis Factor-alpha

Identifiers

PMID23977237
PMCPMC3747052
OpenAlexW1979125528

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.