Evidence map›Paper›PMID 30183492›Full record

ArticlemAbs

A synthetic anti-Frizzled antibody engineered for broadened specificity exhibits enhanced anti-tumor properties.

Zvezdan Pavlovic, Jarrett J Adams, Levi L Blazer, Amandeep K Gakhal, Nick Jarvik, Zachary Steinhart, Mélanie Robitaille, Keith Mascall, James Pan, Stephane Angers and 2 more

Open access · goldAbstract read
In one paragraph

Article in mAbs. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 38 papers.

0numbers the graph read from it
0cells of the map it votes in
38citing papers in PubMed
2.1field-weighted citation impact, top 12% 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, 69 citations in OpenAlex.

  1. Beyond the target: implications of Wnt pathway inhibitors on bone health.Journal of molecular medicine (Berlin, Germany) · 2026
    Review
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  6. Evolutionary conservation and cancer implications of the WNT signaling pathway.Medical oncology (Northwood, London, England) · 2025
    Review
  7. Review
  8. Article
  9. Article
  10. Frizzled receptors: gatekeepers of Wnt signaling in development and disease.Frontiers in cell and developmental biology · 2025
    Review
  11. Article
  12. Article
  13. Review
  14. Article
  15. Review
  16. Article
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  19. Wnt Signaling Inhibitors and Their Promising Role in Tumor Treatment.International journal of molecular sciences · 2023
    Review
  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

12 authors at 2 institutions in 1 country.

Zvezdan Pavlovica Terrence Donnelly Centre for Cellular and Biomolecular Research , University of Toronto , Toronto , Canada.
Jarrett J Adamsa Terrence Donnelly Centre for Cellular and Biomolecular Research , University of Toronto , Toronto , Canada.ORCID 0000-0002-0182-922X
Levi L Blazera Terrence Donnelly Centre for Cellular and Biomolecular Research , University of Toronto , Toronto , Canada.ORCID 0000-0001-9594-4642
Amandeep K Gakhala Terrence Donnelly Centre for Cellular and Biomolecular Research , University of Toronto , Toronto , Canada.ORCID 0000-0003-0617-5787
Nick Jarvika Terrence Donnelly Centre for Cellular and Biomolecular Research , University of Toronto , Toronto , Canada.
Zachary Steinhartb Department of Pharmaceutical Sciences, Leslie Dan Faculty of Pharmacy , University of Toronto , Toronto , Canada.
Mélanie Robitailleb Department of Pharmaceutical Sciences, Leslie Dan Faculty of Pharmacy , University of Toronto , Toronto , Canada.ORCID 0000-0001-9354-5162
Keith Mascallb Department of Pharmaceutical Sciences, Leslie Dan Faculty of Pharmacy , University of Toronto , Toronto , Canada.
James Pana Terrence Donnelly Centre for Cellular and Biomolecular Research , University of Toronto , Toronto , Canada.
Stephane Angersb Department of Pharmaceutical Sciences, Leslie Dan Faculty of Pharmacy , University of Toronto , Toronto , Canada.
Jason Moffata Terrence Donnelly Centre for Cellular and Biomolecular Research , University of Toronto , Toronto , Canada.ORCID 0000-0002-5663-8586
Sachdev S Sidhua Terrence Donnelly Centre for Cellular and Biomolecular Research , University of Toronto , Toronto , Canada.
University of Toronto · CACanadian Institute for Advanced Research · CA

Funding

CIHR 364969CIHR MOP-136944CIHR MOP-93725
6 · The paper itself

Abstract

Secreted Wnt ligands play a major role in the development and progression of many cancers by modulating signaling through cell-surface Frizzled receptors (FZDs). In order to achieve maximal effect on Wnt signaling by targeting the cell surface, we developed a synthetic antibody targeting six of the 10 human FZDs. We first identified an anti-FZD antagonist antibody (F2) with a specificity profile matching that of OMP-18R5, a monoclonal antibody that inhibits growth of many cancers by targeting FZD7, FZD1, FZD2, FZD5 and FZD8. We then used combinatorial antibody engineering by phage display to develop a variant antibody F2.A with specificity broadened to include FZD4. We confirmed that F2.A blocked binding of Wnt ligands, but not binding of Norrin, a ligand that also activates FZD4. Importantly, F2.A proved to be much more efficacious than either OMP-18R5 or F2 in inhibiting the growth of multiple RNF43-mutant pancreatic ductal adenocarcinoma cell lines, including patient-derived cells.

Indexed as

Amino Acid SequenceAntibodies, MonoclonalAntibody SpecificityCarcinoma, Pancreatic DuctalCell Line, TumorCell ProliferationCells, CulturedFrizzled ReceptorsHEK293 CellsHumansImmunoglobulin GPancreatic NeoplasmsProtein BindingProtein IsoformsSequence Homology, Amino AcidAntibodies, MonoclonalFrizzled ReceptorsImmunoglobulin GProtein Isoformsanti-Frizzled synthetic antibodiespancreatic ductal adenocarcinomaphage displayWnt signaling

Identifiers

PMID30183492
PMCPMC6284576
OpenAlexW2891096931

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.