Evidence map›Paper›PMID 31777319›Full record

ArticlemAbs

Structure-based engineering of pH-dependent antibody binding for selective targeting of solid-tumor microenvironment.

Traian Sulea, Nazanin Rohani, Jason Baardsnes, Christopher R Corbeil, Christophe Deprez, Yuneivy Cepero-Donates, Alma Robert, Joseph D Schrag, Marie Parat, Mélanie Duchesne and 3 more

Abstract 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 48 papers.

0numbers the graph read from it
0cells of the map it votes in
48citing 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

48 citing papers in PubMed.

  1. Article
  2. Review
  3. Conditionally Activatable Antibody Platforms: Mechanisms, Modalities, and Clinical Translation Potential.BioDrugs : clinical immunotherapeutics, biopharmaceuticals and gene therapy · 2026
    Review
  4. Article
  5. Article
  6. Article
  7. Article
  8. Article
  9. Improved Structure-Based Histidine pJournal of chemical information and modeling · 2025
    Article
  10. Review
  11. Article
  12. Review
  13. Review
  14. Article
  15. Review
  16. Review
  17. Review
  18. Cancer therapy with antibodies.Nature reviews. Cancer · 2024
    Review
  19. Article
  20. Exploring the next generation of antibody-drug conjugates.Nature reviews. Clinical oncology · 2024
    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

13 authors.

Traian SuleaHuman Health Therapeutics Research Centre, National Research Council Canada, Montreal, Quebec, Canada.ORCID 0000-0001-5301-8261
Nazanin RohaniHuman Health Therapeutics Research Centre, National Research Council Canada, Montreal, Quebec, Canada.
Jason BaardsnesHuman Health Therapeutics Research Centre, National Research Council Canada, Montreal, Quebec, Canada.ORCID 0000-0001-5587-3034
Christopher R CorbeilHuman Health Therapeutics Research Centre, National Research Council Canada, Montreal, Quebec, Canada.ORCID 0000-0001-7657-0286
Christophe DeprezHuman Health Therapeutics Research Centre, National Research Council Canada, Montreal, Quebec, Canada.ORCID 0000-0003-2687-3144
Yuneivy Cepero-DonatesHuman Health Therapeutics Research Centre, National Research Council Canada, Montreal, Quebec, Canada.ORCID 0000-0002-1357-1713
Alma RobertHuman Health Therapeutics Research Centre, National Research Council Canada, Montreal, Quebec, Canada.
Joseph D SchragHuman Health Therapeutics Research Centre, National Research Council Canada, Montreal, Quebec, Canada.
Marie ParatHuman Health Therapeutics Research Centre, National Research Council Canada, Montreal, Quebec, Canada.ORCID 0000-0003-4835-4345
Mélanie DuchesneHuman Health Therapeutics Research Centre, National Research Council Canada, Montreal, Quebec, Canada.
Maria L JaramilloHuman Health Therapeutics Research Centre, National Research Council Canada, Montreal, Quebec, Canada.ORCID 0000-0002-2416-9009
Enrico O PurisimaHuman Health Therapeutics Research Centre, National Research Council Canada, Montreal, Quebec, Canada.
John C ZwaagstraHuman Health Therapeutics Research Centre, National Research Council Canada, Montreal, Quebec, Canada.

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

Recent development of monoclonal antibodies as mainstream anticancer agents demands further optimization of their safety for use in humans. Potent targeting and/or effector activities on normal tissues is an obvious toxicity concern. Optimization of specific tumor targeting could be achieved by taking advantage of the extracellular acidity of solid tumors relative to normal tissues. Here, we applied a structure-based computational approach to engineer anti-human epidermal growth factor receptor 2 (Her2) antibodies with selective binding in the acidic tumor microenvironment. We used an affinity maturation platform in which dual-pH histidine-scanning mutagenesis was implemented for pH selectivity optimization. Testing of a small set of designs for binding to the recombinant Her2 ectodomain led to the identification of antigen-binding fragment (Fab) variants with the desired pH-dependent binding behavior. Binding selectivity toward acidic pH was improved by as much as 25-fold relative to the parental bH1-Fab.

Indexed as

Antibody AffinityAntineoplastic Agents, ImmunologicalCell Line, TumorErb-b2 Receptor Tyrosine KinasesHistidineHumansHydrogen-Ion ConcentrationImmunotherapyMutagenesis, Site-DirectedNeoplasmsProtein BindingProtein ConformationProtein EngineeringTrastuzumabTumor MicroenvironmentAntineoplastic Agents, ImmunologicalERBB2 protein, humanErb-b2 Receptor Tyrosine KinasesHistidineTrastuzumabacidic pH selectivitycell bindingspheroid growthtumor targetingVirtual histidine scanning

Identifiers

PMID31777319
PMCPMC6927761

What OpenQuestion holds

Textmetadata
LicenceCC BY-NC
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.