Evidence map›Paper›PMID 29335534›Full record

ArticleScientific reports2018

Cell-type specific potent Wnt signaling blockade by bispecific antibody.

Nam-Kyung Lee, Yafeng Zhang, Yang Su, Scott Bidlingmaier, Daniel W Sherbenou, Kevin D Ha, Bin Liu

Open access · goldAbstract read
In one paragraph

Article in Scientific reports, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 7 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
7citing papers in PubMed, 1 pooled it
0.6field-weighted citation impact, top 33% 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

7 citing papers in PubMed, 1 synthesis or guideline pooled it, 13 citations in OpenAlex.

  1. Clinical Data for Parametrization ofFrontiers in bioengineering and biotechnology · 2022
    Pooled it
  2. Article
  3. Article
  4. Emerging roles and biomarker potential of WNT6 in human cancers.Cell communication and signaling : CCS · 2024
    Review
  5. Review
  6. Article
  7. Expanding the Boundaries of Biotherapeutics with Bispecific Antibodies.BioDrugs : clinical immunotherapeutics, biopharmaceuticals and gene therapy · 2018
    Review
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 1 institution in 1 country.

Nam-Kyung LeeDepartment of Anesthesia, UCSF Helen Diller Family Comprehensive Cancer Center, 1001 Potrero Ave., 1305, San Francisco, CA, 94110-1305, USA.
Yafeng ZhangDepartment of Anesthesia, UCSF Helen Diller Family Comprehensive Cancer Center, 1001 Potrero Ave., 1305, San Francisco, CA, 94110-1305, USA.
Yang SuDepartment of Anesthesia, UCSF Helen Diller Family Comprehensive Cancer Center, 1001 Potrero Ave., 1305, San Francisco, CA, 94110-1305, USA.
Scott BidlingmaierDepartment of Anesthesia, UCSF Helen Diller Family Comprehensive Cancer Center, 1001 Potrero Ave., 1305, San Francisco, CA, 94110-1305, USA.
Daniel W SherbenouDepartment of Anesthesia, UCSF Helen Diller Family Comprehensive Cancer Center, 1001 Potrero Ave., 1305, San Francisco, CA, 94110-1305, USA.
Kevin D HaDepartment of Anesthesia, UCSF Helen Diller Family Comprehensive Cancer Center, 1001 Potrero Ave., 1305, San Francisco, CA, 94110-1305, USA.
Bin LiuDepartment of Anesthesia, UCSF Helen Diller Family Comprehensive Cancer Center, 1001 Potrero Ave., 1305, San Francisco, CA, 94110-1305, USA. bin.liu@ucsf.edu.
UCSF Helen Diller Family Comprehensive Cancer Center · US

Funding

Mapping a clinically significant internalizing tumor epitope space.R01CA118919 · NCI · UNIVERSITY OF CALIFORNIA, SAN FRANCISCO · PI LIU, BIN · 2006 to 2013
$2.5M
Internalizing human antibody-targeted nanosized siRNA therapeuticsR01CA171315 · NCI · UNIVERSITY OF CALIFORNIA, SAN FRANCISCO · PI LIU, BIN · 2012 to 2016
$1.6M
Identifying antigens bound by novel scFvs targeting all subtypes of mesotheliomaR01CA129491 · NCI · UNIVERSITY OF CALIFORNIA, SAN FRANCISCO · PI LIU, BIN · 2010 to 2013
$1.2M
NCI NIH HHS R01 CA118919NCI NIH HHS R01 CA129491NCI NIH HHS R01 CA171315
6 · The paper itself

Abstract

Cell signaling pathways are often shared between normal and diseased cells. How to achieve cell type-specific, potent inhibition of signaling pathways is a major challenge with implications for therapeutic development. Using the Wnt/β-catenin signaling pathway as a model system, we report here a novel and generally applicable method to achieve cell type-selective signaling blockade. We constructed a bispecific antibody targeting the Wnt co-receptor LRP6 (the effector antigen) and a cell type-associated antigen (the guide antigen) that provides the targeting specificity. We found that the bispecific antibody inhibits Wnt-induced reporter activities with over one hundred-fold enhancement in potency, and in a cell type-selective manner. Potency enhancement is dependent on the expression level of the guide antigen on the target cell surface and the apparent affinity of the anti-guide antibody. Both internalizing and non-internalizing guide antigens can be used, with internalizing bispecific antibody being able to block signaling by all ligands binding to the target receptor due to its removal from the cell surface. It is thus feasible to develop bispecific-based therapeutic strategies that potently and selectively inhibit signaling pathways in a cell type-selective manner, creating opportunity for therapeutic targeting.

Indexed as

Antibodies, Bispecificbeta CateninCell Line, TumorCell ProliferationHumansImmunologic FactorsLow Density Lipoprotein Receptor-Related Protein-6Wnt ProteinsWnt Signaling PathwayAntibodies, Bispecificbeta CateninImmunologic FactorsLow Density Lipoprotein Receptor-Related Protein-6LRP6 protein, humanWnt Proteins

Identifiers

PMID29335534
PMCPMC5768681
OpenAlexW2783865958

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.