Evidence map›Paper›PMID 30721414›Full record

ArticlePharmaceutical research2019

The Binding of Human IgG to Minipig FcγRs - Implications for Preclinical Assessment of Therapeutic Antibodies.

Jerome Egli, Tilman Schlothauer, Christian Spick, Stefan Seeber, Thomas Singer, Alex Odermatt, Antonio Iglesias

Open access · hybridAbstract read
In one paragraph

Article in Pharmaceutical research, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 10 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
10citing papers in PubMed, 1 pooled it
2.0field-weighted citation impact, top 14% 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

10 citing papers in PubMed, 1 synthesis or guideline pooled it, 15 citations in OpenAlex.

  1. FcRn as a Transporter for Nasal Delivery of Biologics: A Systematic Review.International journal of molecular sciences · 2021
    Pooled it
  2. Article
  3. Article
  4. Article
  5. Article
  6. Article
  7. Article
  8. Article
  9. Article
  10. 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 2 institutions in 1 country.

Jerome EgliPharma Research and Early Development (pRED), Pharmaceutical Sciences, Roche Innovation Center Basel, Basel, Switzerland.
Tilman SchlothauerPharma Research and Early Development (pRED), Pharmaceutical Sciences, Roche Innovation Center Munich, Munich, Germany.
Christian SpickPharma Research and Early Development (pRED), Pharmaceutical Sciences, Roche Innovation Center Munich, Munich, Germany.
Stefan SeeberPharma Research and Early Development (pRED), Pharmaceutical Sciences, Roche Innovation Center Munich, Munich, Germany.
Thomas SingerPharma Research and Early Development (pRED), Pharmaceutical Sciences, Roche Innovation Center Basel, Basel, Switzerland.
Alex OdermattDivision of Molecular and Systems Toxicology, Department of Pharmaceutical Sciences, University of Basel, Basel, Switzerland.
Antonio IglesiasPharma Research and Early Development (pRED), Pharmaceutical Sciences, Roche Innovation Center Basel, Basel, Switzerland. antonio.iglesias@roche.com.ORCID http://orcid.org/0000-0002-9528-5883
Roche (Switzerland) · CHUniversity of Basel · CH

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

purposeThe Göttingen minipig is a relevant non-rodent species for regulatory toxicological studies. Yet, its use with therapeutic antibodies has been limited by the unknown binding properties of human immunoglobulins (huIgG) to porcine Fc gamma receptors (poFcγR) influencing safety and efficacy readouts. Therefore, knowing IgG-FcγR interactions in the animal model is a prerequisite for the use of minipigs in preclinical safety and efficacy studies with therapeutic antibodies.

methodsHere, we describe the cloning and expression of poFcγRs and their interactions with free and complexed human therapeutic IgG1 by surface plasmon resonance and flow cytometry.

resultsWe show here that poFcγRIa, poFcγRIIa, and poFcγRIIb bind huIgG1 antibodies with comparable affinities as corresponding huFcγRs. Importantly, poFcγRs bind huIgG immune complexes with high avidity, thus probably allowing human-like effector functions. However, poFcγRIIIa binds poIgG1a but not to huIgG1.

conclusionsThe lack of binding of poFcγRIIIa to huIgG1 might cause underestimation of FcγRIIIa-mediated efficacy or toxicity as mediated by porcine natural killer cells. Therefore, the suitability of minipigs in preclinical studies with human therapeutic antibodies has to be assessed case by case. Our results facilitate the use of Göttingen minipigs for assessment of human therapeutic antibodies in preclinical studies.

Indexed as

AnimalsAntibody AffinityHumansImmunoglobulin Fc FragmentsImmunoglobulin GKiller Cells, NaturalProtein BindingReceptors, IgGSwineSwine, MiniatureImmunoglobulin Fc FragmentsImmunoglobulin GReceptors, IgGantibody effector functionFcγRGöttingen minipigIgGinteraction map

Identifiers

PMID30721414
PMCPMC6373530
OpenAlexW2913970656

What OpenQuestion holds

Textmetadata
LicenceCC BY
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.