Evidence map›Paper›PMID 31133742›Full record

ArticleNature biotechnology2019

A coiled-coil masking domain for selective activation of therapeutic antibodies.

Vivian H Trang, Xinqun Zhang, Roma C Yumul, Weiping Zeng, Ivan J Stone, Serena W Wo, Melissa M Dominguez, Julia H Cochran, Jessica K Simmons, Maureen C Ryan and 3 more

Abstract read
PubMed Publisher
In one paragraph

Article in Nature biotechnology, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 56 papers.

0numbers the graph read from it
0cells of the map it votes in
56citing 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

56 citing papers in PubMed.

  1. Article
  2. Article
  3. Article
  4. Article
  5. Article
  6. Review
  7. Conditionally Activatable Antibody Platforms: Mechanisms, Modalities, and Clinical Translation Potential.BioDrugs : clinical immunotherapeutics, biopharmaceuticals and gene therapy · 2026
    Review
  8. Review
  9. Article
  10. Article
  11. Article
  12. Article
  13. Article
  14. Article
  15. A facile yeast-display approach for antibody mask discovery.Protein engineering, design & selection : PEDS · 2025
    Article
  16. Review
  17. Article
  18. Article
  19. 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

13 authors.

Vivian H TrangDepartment of Protein Sciences, Seattle Genetics Inc., Bothell, WA, USA.
Xinqun ZhangDepartment of Protein Sciences, Seattle Genetics Inc., Bothell, WA, USA.
Roma C YumulDepartment of Nonclinical Science, Seattle Genetics Inc., Bothell, WA, USA.
Weiping ZengDepartment of Nonclinical Science, Seattle Genetics Inc., Bothell, WA, USA.
Ivan J StoneDepartment of Nonclinical Science, Seattle Genetics Inc., Bothell, WA, USA.
Serena W WoDepartment of Protein Sciences, Seattle Genetics Inc., Bothell, WA, USA.
Melissa M DominguezDepartment of Protein Sciences, Seattle Genetics Inc., Bothell, WA, USA.
Julia H CochranDepartment of Protein Sciences, Seattle Genetics Inc., Bothell, WA, USA.
Jessica K SimmonsDepartment of Nonclinical Science, Seattle Genetics Inc., Bothell, WA, USA.
Maureen C RyanDepartment of Antibody Discovery, Seattle Genetics Inc., Bothell, WA, USA.
Robert P LyonDepartment of Protein Sciences, Seattle Genetics Inc., Bothell, WA, USA.
Peter D SenterDepartment of Chemistry, Seattle Genetics Inc., Bothell, WA, USA.
Matthew R LevengoodDepartment of Protein Sciences, Seattle Genetics Inc., Bothell, WA, USA. mlevengood@seagen.com.ORCID http://orcid.org/0000-0002-3762-9983

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

The use of monoclonal antibodies in cancer therapy is limited by their cross-reactivity to healthy tissue. Tumor targeting has been improved by generating masked antibodies that are selectively activated in the tumor microenvironment, but each such antibody necessitates a custom design. Here, we present a generalizable approach for masking the binding domains of antibodies with a heterodimeric coiled-coil domain that sterically occludes the complementarity-determining regions. On exposure to tumor-associated proteases, such as matrix metalloproteinases 2 and 9, the coiled-coil peptides are cleaved and antigen binding is restored. We test multiple coiled-coil formats and show that the optimized masking domain is broadly applicable to antibodies of interest. Our approach prevents anti-CD3-associated cytokine release in mice and substantially improves circulation half-life by protecting the antibody from an antigen sink. When applied to antibody-drug conjugates, our masked antibodies are preferentially unmasked at the tumor site and have increased anti-tumor efficacy compared with unmasked antibodies in mouse models of cancer.

Indexed as

AnimalsAntibodies, MonoclonalCell SurvivalCytokinesHEK293 CellsHumansImmunoconjugatesIntegrinsMiceModels, MolecularNeoplasmsProtein ConformationProtein DomainsAntibodies, MonoclonalCytokinesImmunoconjugatesIntegrins

Identifiers

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.