Evidence map›Paper›PMID 35799328›Full record

ArticlemAbs

Mechanistic insights into the rational design of masked antibodies.

Carolina T Orozco, Manuela Bersellini, Lorraine M Irving, Wesley W Howard, David Hargreaves, Paul W A Devine, Elise Siouve, Gareth J Browne, Nicholas J Bond, Jonathan J Phillips and 2 more

Open access · goldAbstract 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 9 papers.

0numbers the graph read from it
0cells of the map it votes in
9citing papers in PubMed
1.6field-weighted citation impact, top 18% 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

9 citing papers in PubMed, 11 citations in OpenAlex.

  1. Article
  2. Protein engineering: status report.Protein engineering, design & selection : PEDS · 2026
    Review
  3. Journal of the American Chemical Society · 2025
    Article
  4. Article
  5. Article
  6. Article
  7. Article
  8. Fibroblasts: invigorated targets in pre-metastatic niche formation.International journal of biological sciences · 2024
    Review
  9. 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

12 authors at 4 institutions in 3 countries.

Carolina T OrozcoYusuf Hamied Department of Chemistry, University of Cambridge, Cambridge, UK.ORCID 0000-0001-7274-8833
Manuela BerselliniBiologics Engineering, R&D, AstraZeneca, Cambridge, UK.
Lorraine M IrvingBiologics Engineering, R&D, AstraZeneca, Cambridge, UK.ORCID 0000-0002-0816-5729
Wesley W HowardAnalytical Sciences, Biopharmaceutical Development, R&D, AstraZeneca, Gaithersburg, MD, USA.ORCID 0000-0001-8314-8454
David HargreavesDiscovery Sciences, R&D, AstraZeneca, Cambridge, UK.ORCID 0000-0003-4441-0039
Paul W A DevineAnalytical Sciences, Biopharmaceutical Development, R&D, AstraZeneca, Cambridge, UK.
Elise SiouveBiologics Engineering, R&D, AstraZeneca, Cambridge, UK.ORCID 0000-0001-8254-6610
Gareth J BrowneBiologics Engineering, R&D, AstraZeneca, Cambridge, UK.ORCID 0000-0002-4579-2625
Nicholas J BondAnalytical Sciences, Biopharmaceutical Development, R&D, AstraZeneca, Cambridge, UK.ORCID 0000-0002-0312-7360
Jonathan J PhillipsLiving Systems Institute, University of Exeter, Exeter, UK.ORCID 0000-0002-5361-9582
Peter RavnBiologics Engineering, R&D, AstraZeneca, Cambridge, UK.ORCID 0000-0003-3032-9037
Sophie E JacksonYusuf Hamied Department of Chemistry, University of Cambridge, Cambridge, UK.ORCID 0000-0002-7470-9800
AstraZeneca (United Kingdom) · GBAstraZeneca (United States) · USUniversity of Cambridge · GBUniversity of Exeter · GB

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

Although monoclonal antibodies have greatly improved cancer therapy, they can trigger side effects due to on-target, off-tumor toxicity. Over the past decade, strategies have emerged to successfully mask the antigen-binding site of antibodies, such that they are only activated at the relevant site, for example, after proteolytic cleavage. However, the methods for designing an ideal affinity-based mask and what parameters are important are not yet well understood. Here, we undertook mechanistic studies using three masks with different properties and identified four critical factors: binding site and affinity, as well as association and dissociation rate constants, which also played an important role. HDX-MS was used to identify the location of binding sites on the antibody, which were subsequently validated by obtaining a high-resolution crystal structure for one of the mask-antibody complexes. These findings will inform future designs of optimal affinity-based masks for antibodies and other therapeutic proteins.

Indexed as

Antibodies, MonoclonalAntibody AffinityBinding SitesAntibodies, MonoclonalMasked antibodiesoff-tumor cytotoxicitypro-antibodypro-biologicspro-drugprotein designprotein-protein interaction

Identifiers

PMID35799328
PMCPMC9272835
OpenAlexW4284881222

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.