Evidence map›Paper›PMID 36505931›Full record

ArticleiScience2022

Antibody specificity against highly conserved membrane protein Claudin 6 driven by single atomic contact point.

Brad Screnci, Lewis J Stafford, Trevor Barnes, Kristen Shema, Samantha Gilman, Rebecca Wright, Suzie Al Absi, Tim Phillips, Charles Azuelos, Katherine Slovik and 6 more

Open access · goldAbstract read
In one paragraph

Article in iScience, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 14 papers.

0numbers the graph read from it
0cells of the map it votes in
14citing papers in PubMed
1.0field-weighted citation impact, top 26% 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

14 citing papers in PubMed, 12 citations in OpenAlex.

  1. Article
  2. Targeting claudins in cancer.Nature reviews. Drug discovery · 2026
    Review
  3. Review
  4. Article
  5. Review
  6. Article
  7. Article
  8. Article
  9. Discovery of Therapeutic Antibodies Targeting Complex Multi-Spanning Membrane Proteins.BioDrugs : clinical immunotherapeutics, biopharmaceuticals and gene therapy · 2024
    Review
  10. Applications of Flow Cytometry in Drug Discovery and Translational Research.International journal of molecular sciences · 2024
    Review
  11. Review
  12. Methods for Engineering Binders to Multi-Pass Membrane Proteins.Bioengineering (Basel, Switzerland) · 2023
    Review
  13. Review
  14. 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

16 authors at 1 institution in 1 country.

Brad ScrenciIntegral Molecular, 3711 Market Street, Suite 900, Philadelphia, PA 19104, USA.
Lewis J StaffordIntegral Molecular, 3711 Market Street, Suite 900, Philadelphia, PA 19104, USA.
Trevor BarnesIntegral Molecular, 3711 Market Street, Suite 900, Philadelphia, PA 19104, USA.
Kristen ShemaIntegral Molecular, 3711 Market Street, Suite 900, Philadelphia, PA 19104, USA.
Samantha GilmanIntegral Molecular, 3711 Market Street, Suite 900, Philadelphia, PA 19104, USA.
Rebecca WrightIntegral Molecular, 3711 Market Street, Suite 900, Philadelphia, PA 19104, USA.
Suzie Al AbsiIntegral Molecular, 3711 Market Street, Suite 900, Philadelphia, PA 19104, USA.
Tim PhillipsIntegral Molecular, 3711 Market Street, Suite 900, Philadelphia, PA 19104, USA.
Charles AzuelosIntegral Molecular, 3711 Market Street, Suite 900, Philadelphia, PA 19104, USA.
Katherine SlovikIntegral Molecular, 3711 Market Street, Suite 900, Philadelphia, PA 19104, USA.
Paige MurphyIntegral Molecular, 3711 Market Street, Suite 900, Philadelphia, PA 19104, USA.
Daniel B HarmonIntegral Molecular, 3711 Market Street, Suite 900, Philadelphia, PA 19104, USA.
Tom CharpentierIntegral Molecular, 3711 Market Street, Suite 900, Philadelphia, PA 19104, USA.
Benjamin J DoranzIntegral Molecular, 3711 Market Street, Suite 900, Philadelphia, PA 19104, USA.
Joseph B RuckerIntegral Molecular, 3711 Market Street, Suite 900, Philadelphia, PA 19104, USA.
Ross ChambersIntegral Molecular, 3711 Market Street, Suite 900, Philadelphia, PA 19104, USA.
Integral Molecular (United States) · US

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

The tight junction protein claudin 6 (CLDN6) is differentially expressed on cancer cells with almost no expression in healthy tissue. However, achieving therapeutic MAb specificity for this 4 transmembrane protein is challenging because it is nearly identical to the widely expressed CLDN9, with only 3 extracellular amino acids different. Most other CLDN6 MAbs, including those in clinical development are cross-reactive with CLDN9, and several trials have now been stopped. Here we isolated rare MAbs that bind CLDN6 with up to picomolar affinity and display minimal cross-reactivity with CLDN9, 22 other CLDN family members, or across the human membrane proteome. Amino acid-level epitope mapping distinguished the binding sites of our MAbs from existing clinical-stage MAbs. Atomic-level epitope mapping identified the structural mechanism by which our MAbs differentiate CLDN6 and CLDN9 through steric hindrance at a single molecular contact point, the γ carbon on CLDN6 residue Q156.

Indexed as

BiochemistryCancerImmunology

Identifiers

PMID36505931
PMCPMC9732412
OpenAlexW4309891838

What OpenQuestion holds

Textmetadata
LicenceCC BY-NC-ND
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.