Evidence map›Paper›PMID 28431161›Full record

ArticleProtein engineering, design & selection : PEDS2017

Engineering a high-affinity peptide binding site into the anti-CEA mAb M5A.

Cindy Zer, Kendra N Avery, Kassondra Meyer, Leah Goodstein, Krzysztof P Bzymek, Gagandeep Singh, John C Williams

Abstract read
In one paragraph

Article in Protein engineering, design & selection : PEDS, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 9 papers.

0numbers the graph read from it
0cells of the map it votes in
9citing papers in PubMed
–field-weighted citation impact
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

9 citing papers in PubMed.

  1. Article
  2. The Current Landscape of Modular CAR T Cells.International journal of molecular sciences · 2025
    Review
  3. Article
  4. Article
  5. Article
  6. Article
  7. Article
  8. Article
  9. Meditope-Fab interaction: threading the hole.Acta crystallographica. Section F, Structural biology communications · 2017
    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

7 authors.

Cindy ZerDepartment of Molecular Medicine, Beckman Research Institute at City of Hope.
Kendra N AveryDepartment of Molecular Medicine, Beckman Research Institute at City of Hope.
Kassondra MeyerDepartment of Molecular Medicine, Beckman Research Institute at City of Hope.
Leah GoodsteinDepartment of Molecular Medicine, Beckman Research Institute at City of Hope.
Krzysztof P BzymekDepartment of Molecular Medicine, Beckman Research Institute at City of Hope.
Gagandeep SinghDepartment of Surgery, City of Hope National Medical Center 1500 Duarte Road, Duarte, CA 91010, USA.
John C WilliamsDepartment of Molecular Medicine, Beckman Research Institute at City of Hope.

Funding

Transgenic Mouse FacilityP30CA033572 · NCI · CITY OF HOPE/BECKMAN RESEARCH INSTITUTE · PI STANLEY R. HAMILTON · 1985 to 2026
$86.3M
Monoclonal Antibody-based Prodrugs - Novel Tools for Cancer TherapyR21CA135216 · NCI · THOMAS JEFFERSON UNIVERSITY · PI RODECK, ULRICH, WILLIAMS, JOHN CHARLES · 2010 to 2011
$392k
NCI NIH HHS P30 CA033572NCI NIH HHS R21 CA135216
6 · The paper itself

Abstract

We have previously identified a cyclic peptide called meditope which binds to the central cavity of the Fab portion of cetuximab and shown that this peptide binding site can be grafted, or 'meditope-enabled', onto trastuzumab. This peptide has been shown to act as a hitch for the non-covalent attachment of imaging agents to meditope-enabled antibodies. Herein, we explore the process of grafting this peptide binding site onto M5A, an anti-CEA antibody in clinical trials for cancer diagnostics. In order to explore the contributions of the amino acids, we sequentially introduced pairs of amino acid substitutions into the Fab and then we reverse-substituted key residues in the presence of the other substitutions. We demonstrate that Pro40Thr, Gly41Asn, Phe83Ile and Thr85Asp in the light chain are sufficient to recreate the meditope binding site in M5A with single-digit micromolar affinity. We show that Pro40 abrogates peptide binding in the presence of the other 12 residue substitutions, and that the presence of all 13 substitutions does not interfere with antibody:antigen recognition. Collectively, these studies provide detailed insight for defining and fine-tuning the binding affinity of the meditope binding site within an antibody.

Indexed as

Antibodies, MonoclonalBinding SitesCarcinoembryonic AntigenCell LineHumansModels, MolecularPeptidesProtein BindingProtein EngineeringAntibodies, MonoclonalCarcinoembryonic AntigenPeptidesantibody-drug conjugateantibody engineeringCEAgraftingmeditope

Identifiers

PMID28431161
PMCPMC5914451

What OpenQuestion holds

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Registered trials

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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.