Evidence map›Paper›PMID 31267741›Full record

ArticleJournal of proteome research2019

Pharmacokinetic Analysis of a Novel Human EGFRvIII:CD3 Bispecific Antibody in Plasma and Whole Blood Using a High-Resolution Targeted Mass Spectrometry Approach.

Teilo H Schaller, Matthew W Foster, J Will Thompson, Ivan Spasojevic, Deimante Normantaite, M Arthur Moseley, Luis Sanchez-Perez, John H Sampson

Open access · greenAbstract read
In one paragraph

Article in Journal of proteome research, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 18 papers.

0numbers the graph read from it
0cells of the map it votes in
18citing papers in PubMed
1.7field-weighted citation impact, top 16% 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

18 citing papers in PubMed, 21 citations in OpenAlex.

  1. Article
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  8. Review
  9. Article
  10. Review
  11. Article
  12. Review
  13. Neural stem cells secreting bispecific T cell engager to induce selective antiglioma activity.Proceedings of the National Academy of Sciences of the United States of America · 2021
    Article
  14. Updated Insights on EGFR Signaling Pathways in Glioma.International journal of molecular sciences · 2021
    Review
  15. Article
  16. Toward Drug-Like Multispecific Antibodies by Design.International journal of molecular sciences · 2020
    Review
  17. Review
  18. 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

8 authors at 2 institutions in 1 country.

Teilo H SchallerPreston Robert Tisch Brain Tumor Center , Duke University Medical Center , Durham , North Carolina , United States.ORCID 0000-0002-5036-5820
Matthew W FosterDuke Proteomics and Metabolomics Shared Resource, Duke Center for Genomic and Computational Biology , Duke University , Durham , North Carolina , United States.
J Will ThompsonDuke Proteomics and Metabolomics Shared Resource, Duke Center for Genomic and Computational Biology , Duke University , Durham , North Carolina , United States.ORCID 0000-0001-6567-1268
Ivan SpasojevicDuke Cancer Institute PK/PD Core Laboratory , Durham , North Carolina , United States.
Deimante NormantaitePreston Robert Tisch Brain Tumor Center , Duke University Medical Center , Durham , North Carolina , United States.
M Arthur MoseleyDuke Proteomics and Metabolomics Shared Resource, Duke Center for Genomic and Computational Biology , Duke University , Durham , North Carolina , United States.
Luis Sanchez-PerezPreston Robert Tisch Brain Tumor Center , Duke University Medical Center , Durham , North Carolina , United States.
John H SampsonPreston Robert Tisch Brain Tumor Center , Duke University Medical Center , Durham , North Carolina , United States.
Duke Medical Center · USDuke University · US

Funding

Women's Cancer Research ProgramP30CA014236 · NCI · DUKE UNIVERSITY · PI DONNA NIEDZWIECKI · 1985 to 2026
$174.8M
Human EGFRvIII-specific BiTE for the treatment of GlioblastomaU01NS090284 · NINDS · DUKE UNIVERSITY · PI SAMPSON, JOHN H. · 2015 to 2019
$5.2M
EGFRvIII-targeted Bispecific T cell Engagers for brain tumorsR01NS085412 · NINDS · DUKE UNIVERSITY · PI SAMPSON, JOHN H. · 2013 to 2017
$2.0M
NCI NIH HHS P30 CA014236NINDS NIH HHS R01 NS085412NINDS NIH HHS U01 NS090284
6 · The paper itself

Abstract

Bispecific single chain antibody fragments (bi-scFv) represent an emerging class of biotherapeutics. We recently developed a fully human bi-scFv (EGFRvIII:CD3 bi-scFv) with the goal of redirecting CD3-expressing T cells to recognize and destroy malignant, EGFRvIII-expressing glioma. In mice, we showed that EGFRvIII:CD3 bi-scFv effectively treats orthotopic patient-derived malignant glioma and syngeneic glioblastoma. Here, we developed a targeted assay for pharmacokinetic (PK) analysis of EGFRvIII:CD3 bi-scFv, a necessary step in the drug development process. Using microflow liquid chromatography coupled to a high resolution parallel reaction monitoring mass spectrometry, and data analysis in Skyline, we developed a bottom-up proteomic assay for quantification of EGFRvIII:CD3 bi-scFv in both plasma and whole blood. Importantly, a protein calibrator, along with stable isotope-labeled EGFRvIII:CD3 bi-scFv protein, were used for absolute quantification. A PK analysis in a CD3 humanized mouse revealed that EGFRvIII:CD3 bi-scFv in plasma and whole blood has an initial half-life of ∼8 min and a terminal half-life of ∼2.5 h. Our results establish a sensitive, high-throughput assay for direct quantification of EGFRvIII:CD3 bi-scFv without the need for immunoaffinity enrichment. Moreover, these pharmacokinetic parameters will guide drug optimization and dosing regimens in future IND-enabling and phase I studies of EGFRvIII:CD3 bi-scFv.

Indexed as

AnimalsAntibodies, BispecificCD3 ComplexCell Line, TumorChromatography, LiquidErbB ReceptorsGlioblastomaHumansMass SpectrometryMiceProteomicsT-LymphocytesXenograft Model Antitumor AssaysAntibodies, BispecificCD3 Complexepidermal growth factor receptor VIIIErbB Receptorsabsolute quantificationbiotherapeuticbispecific antibodygliomamass spectrometryparallel reaction monitoringpharmacokinetic analysisstable isotope labeled proteintargeted proteomics

Identifiers

PMID31267741
PMCPMC7325320
OpenAlexW2954493613

What OpenQuestion holds

Textmetadata
LicenceTDM
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.