Evidence map›Paper›PMID 26260789›Full record

ArticleThe Journal of biological chemistry2015

Impact of Cell-surface Antigen Expression on Target Engagement and Function of an Epidermal Growth Factor Receptor × c-MET Bispecific Antibody.

Stephen W Jarantow, Barbara S Bushey, Jose R Pardinas, Ken Boakye, Eilyn R Lacy, Renouard Sanders, Manuel A Sepulveda, Sheri L Moores, Mark L Chiu

Open access · hybridAbstract read
In one paragraph

Article in The Journal of biological chemistry, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 38 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
38citing papers in PubMed, 1 pooled it
3.8field-weighted citation impact, top 7% 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

38 citing papers in PubMed, 1 synthesis or guideline pooled it, 57 citations in OpenAlex.

  1. Pooled it
  2. Article
  3. Review
  4. Article
  5. Review
  6. Article
  7. Bispecific Antibodies in Solid Tumors: Advances and Challenges.International journal of molecular sciences · 2025
    Review
  8. The User's Guide to Amivantamab.Targeted oncology · 2025
    Review
  9. Article
  10. Review
  11. Article
  12. Review
  13. Review
  14. Article
  15. Article
  16. Review
  17. Article
  18. Review
  19. Article
  20. 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

9 authors at 1 institution in 1 country.

Stephen W JarantowFrom Janssen Research and Development, LLC, Spring House, Pennsylvania 19477 and.
Barbara S BusheyFrom Janssen Research and Development, LLC, Spring House, Pennsylvania 19477 and.
Jose R PardinasFrom Janssen Research and Development, LLC, Spring House, Pennsylvania 19477 and.
Ken BoakyeFrom Janssen Research and Development, LLC, Spring House, Pennsylvania 19477 and.
Eilyn R LacyFrom Janssen Research and Development, LLC, Spring House, Pennsylvania 19477 and.
Renouard SandersJanssen Diagnostics, Janssen Research and Development, Huntingdon Valley, Pennsylvania 19104.
Manuel A SepulvedaFrom Janssen Research and Development, LLC, Spring House, Pennsylvania 19477 and.
Sheri L MooresFrom Janssen Research and Development, LLC, Spring House, Pennsylvania 19477 and.
Mark L ChiuFrom Janssen Research and Development, LLC, Spring House, Pennsylvania 19477 and MChiu@its.jnj.com.
Janssen (United States) · US

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

The efficacy of engaging multiple drug targets using bispecific antibodies (BsAbs) is affected by the relative cell-surface protein levels of the respective targets. In this work, the receptor density values were correlated to the in vitro activity of a BsAb (JNJ-61186372) targeting epidermal growth factor receptor (EGFR) and hepatocyte growth factor receptor (c-MET). Simultaneous binding of the BsAb to both receptors was confirmed in vitro. By using controlled Fab-arm exchange, a set of BsAbs targeting EGFR and c-MET was generated to establish an accurate receptor quantitation of a panel of lung and gastric cancer cell lines expressing heterogeneous levels of EGFR and c-MET. EGFR and c-MET receptor density levels were correlated to the respective gene expression levels as well as to the respective receptor phosphorylation inhibition values. We observed a bias in BsAb binding toward the more highly expressed of the two receptors, EGFR or c-MET, which resulted in the enhanced in vitro potency of JNJ-61186372 against the less highly expressed target. On the basis of these observations, we propose an avidity model of how JNJ-61186372 engages EGFR and c-MET with potentially broad implications for bispecific drug efficacy and design.

Indexed as

Gene Expression RegulationMolecular Targeted TherapyAntibodies, BispecificAntigens, SurfaceCell Line, TumorErbB ReceptorsHumansImmunoglobulin Fab FragmentsModels, MolecularMutationPhosphorylationProtein MultimerizationProtein Structure, QuaternaryProto-Oncogene Proteins c-metRNA, MessengerAntibodies, BispecificAntigens, SurfaceEGFR protein, humanErbB ReceptorsImmunoglobulin Fab FragmentsMET protein, humanProto-Oncogene Proteins c-metRNA, Messengerbispecific antibodycancer therapycell-surface receptorc-METepidermal growth factor (EGF)epidermal growth factor receptor (EGFR)hepatocyte growth factor/scatter factor (HGF/SF)quantitative flow cytometry

Identifiers

PMID26260789
PMCPMC4598982
OpenAlexW2262441789

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.