Evidence map›Paper›PMID 24401277›Full record

ArticleThe Journal of clinical investigation2014

Human IgG Fc domain engineering enhances antitoxin neutralizing antibody activity.

Stylianos Bournazos, Siu-Kei Chow, Nareen Abboud, Arturo Casadevall, Jeffrey V Ravetch

Abstract read
In one paragraph

Article in The Journal of clinical investigation, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 42 papers.

0numbers the graph read from it
0cells of the map it votes in
42citing papers in PubMed
7.0field-weighted citation impact, top 3% 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

42 citing papers in PubMed, 62 citations in OpenAlex.

  1. Review
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  7. A Holistic Review of the Preclinical Landscape for Long-Acting Anti-infective Drugs Using HIV as a Paradigm.Clinical infectious diseases : an official publication of the Infectious Diseases Society of America · 2022
    Review
  8. Review
  9. Article
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  15. Differential requirements for FcγR engagement by protective antibodies against Ebola virus.Proceedings of the National Academy of Sciences of the United States of America · 2019
    Article
  16. Functional diversification of IgGs through Fc glycosylation.The Journal of clinical investigation · 2019
    Review
  17. Article
  18. Article
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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

5 authors at 2 institutions in 1 country.

Stylianos Bournazos
Siu-Kei Chow
Nareen Abboud
Arturo Casadevall
Jeffrey V Ravetch
Yeshiva University · USRockefeller University · US

Funding

Viral Pathogenesis and TherapeuticsU54AI057158 · NIAID · WADSWORTH CENTER · PI LIPKIN, W. IAN · 2003 to 2014
$100.8M
NIAID NIH HHS 5U54AI057158NIAID NIH HHS U54 AI057158
6 · The paper itself

Abstract

The effector activity of antibodies is dependent on engagement with Fcγ receptors (FcγRs) and activation of the associated intracellular signaling pathways. Preclinical evaluation of therapeutic humanized or chimeric mAbs to study the interactions of their Fc regions with FcγRs is hampered by substantial structural and functional FcγR diversity among species. In this report, we used mice expressing only human FcγRs to evaluate the contribution of FcγR-mediated pathways to the neutralizing activity of an anti-anthrax toxin chimeric mAb. We observed that the protective activity of this mAb was highly dependent upon FcγR engagement, with minimal protection against anthrax toxin observed in FcγR-deficient mice following mAb administration. We generated anti-anthrax toxin mAbs with specific Fc domain variants with selectively enhanced affinity for particular human FcγRs and assessed their activity in FcγR-humanized mice. We determined that Fc domain variants that were capable of selectively engaging activating FcγRs substantially enhanced the in vitro and in vivo activity of anthrax toxin-neutralizing antibodies. These findings indicate that the application of Fc domain engineering is a feasible strategy to enhance toxin-neutralizing activity and suggest that engineered antitoxin antibodies will have improved therapeutic efficacy.

Indexed as

AnimalsAnthraxAntibodies, MonoclonalAntibodies, NeutralizingAntibody-Dependent Cell CytotoxicityAntigens, BacterialAntitoxinsBacterial ToxinsEnzyme-Linked Immunosorbent AssayHEK293 CellsHumansImmunoglobulin GInhibitory Concentration 50MiceMice, TransgenicProtein Engineeringanthrax toxinAntibodies, MonoclonalAntibodies, NeutralizingAntigens, BacterialAntitoxinsBacterial ToxinsImmunoglobulin GReceptors, IgGRecombinant Proteins

Identifiers

PMID24401277
PMCPMC3904629
OpenAlexW2079435298

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.