Evidence map›Paper›PMID 32125783›Full record

ArticlePharmacology research & perspectives2020

Complex formation of anti-VEGF-C with VEGF-C released during blood coagulation resulted in an artifact in its serum pharmacokinetics.

Daniela Bumbaca Yadav, Arthur E Reyes, Priyanka Gupta, Jean-Michel Vernes, Y Gloria Meng, Michelle G Schweiger, Shannon L Stainton, Germaine Fuh, Paul J Fielder, Amrita V Kamath and 1 more

Open access · goldAbstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Pharmacology research & perspectives, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 3 papers.

0numbers the graph read from it
0cells of the map it votes in
3citing papers in PubMed
0.3field-weighted citation impact, top 47% 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

3 citing papers in PubMed, 4 citations in OpenAlex.

  1. Review
  2. Review
  3. 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

11 authors at 3 institutions in 2 countries.

Daniela Bumbaca YadavPreclinical and Translational Pharmacokinetics and Pharmacodynamics Department, Genentech, Inc., South San Francisco, CA, USA.
Arthur E ReyesPreclinical and Translational Pharmacokinetics and Pharmacodynamics Department, Genentech, Inc., South San Francisco, CA, USA.
Priyanka GuptaPreclinical and Translational Pharmacokinetics and Pharmacodynamics Department, Genentech, Inc., South San Francisco, CA, USA.
Jean-Michel VernesBiochemical and Cellular Pharmacology Department, Genentech, Inc., South San Francisco, CA, USA.
Y Gloria MengBiochemical and Cellular Pharmacology Department, Genentech, Inc., South San Francisco, CA, USA.
Michelle G SchweigerSafety Assessment Department, Genentech, Inc., South San Francisco, CA, USA.
Shannon L StaintonSafety Assessment Department, Genentech, Inc., South San Francisco, CA, USA.
Germaine FuhAntibody Engineering Department, Genentech, Inc., South San Francisco, CA, USA.
Paul J FielderPreclinical and Translational Pharmacokinetics and Pharmacodynamics Department, Genentech, Inc., South San Francisco, CA, USA.
Amrita V KamathPreclinical and Translational Pharmacokinetics and Pharmacodynamics Department, Genentech, Inc., South San Francisco, CA, USA.
Ben-Quan ShenPreclinical and Translational Pharmacokinetics and Pharmacodynamics Department, Genentech, Inc., South San Francisco, CA, USA.ORCID 0000-0002-8214-6825
Biochemical Society · GBImpact Assessment · USResearch & Diagnostic Antibodies (United States) · US

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

A phage-derived human monoclonal antibody against VEGF-C was developed as a potential anti-tumor therapeutic and exhibited fast clearance in preclinical species, with notably faster clearance in serum than in plasma. The purpose of this work was to understand the factors contributing to its fast clearance. In vitro incubations in animal and human blood, plasma, and serum were conducted with radiolabeled anti-VEGF-C to determine potential protein and cell-based interactions with the antibody as well as any matrix-dependent recovery dependent upon the matrix. A tissue distribution study was conducted in mice with and without heparin infusion in order to identify a tissue sink and determine whether heparin could affect antibody recovery from serum and/or plasma. Incubation of radiolabeled anti-VEGF-C in human and animal blood, plasma, or serum revealed that the antibody formed a complex with an endogenous protein, likely VEGF-C. This complex was trapped within the blood clot during serum preparation from blood, but not within the blood cell pellet during plasma preparation. Low level heparin infusion in mice slowed down clot formation during serum preparation and allowed for better recovery of the radiolabeled antibody in serum. No tissue sink was found in mice. Thus, during this characterization, we determined that the blood sampling matrix greatly impacted the amount of antibody recovered in the samples, therefore, altering its derived pharmacokinetic parameters. Target biology should be considered when selecting appropriate sampling matrices for PK analysis.

Indexed as

AnimalsAntibodies, MonoclonalArtifactsBlood CoagulationFemaleHumansMacaca fascicularisMice, NudeRats, Sprague-DawleyTissue DistributionVascular Endothelial Growth Factor CAntibodies, MonoclonalVascular Endothelial Growth Factor Cimmunocomplexmatrix effectspharmacokineticsVEGF-C

Identifiers

PMID32125783
PMCPMC7053556
OpenAlexW3009390223

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.