Evidence map›Paper›PMID 26546838›Full record

ArticleBiochimie2016

In vivo imaging of protease activity by Probody therapeutic activation.

Kenneth R Wong, Elizabeth Menendez, Charles S Craik, W Michael Kavanaugh, Olga Vasiljeva

Open access · hybridAbstract read
In one paragraph

Article in Biochimie, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 13 papers.

0numbers the graph read from it
0cells of the map it votes in
13citing papers in PubMed
0.6field-weighted citation impact, top 33% 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

13 citing papers in PubMed, 29 citations in OpenAlex.

  1. Article
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  11. Masked Chimeric Antigen Receptor for Tumor-Specific Activation.Molecular therapy : the journal of the American Society of Gene Therapy · 2017
    Article
  12. Article
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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

5 authors at 2 institutions in 1 country.

Kenneth R WongCytomX Therapeutics, Inc., 343 Oyster Point Blvd, South San Francisco, CA 94080, USA.
Elizabeth MenendezCytomX Therapeutics, Inc., 343 Oyster Point Blvd, South San Francisco, CA 94080, USA.
Charles S CraikDepartment of Pharmaceutical Chemistry, University of California, 600 16th Street, San Francisco, CA 94158, USA.
W Michael KavanaughCytomX Therapeutics, Inc., 343 Oyster Point Blvd, South San Francisco, CA 94080, USA.
Olga VasiljevaCytomX Therapeutics, Inc., 343 Oyster Point Blvd, South San Francisco, CA 94080, USA. Electronic address: olga@cytomx.com.
CytomX Therapeutics (United States) · USUniversity of California, San Francisco · US

Funding

Renewable antibodies to secreted proteins and single and multi-pass cell surfaceP41CA196276 · NCI · UNIVERSITY OF CALIFORNIA, SAN FRANCISCO · PI WELLS, JAMES A · 2014 to 2018
$5.8M
NCI NIH HHS 1P41CA196276NCI NIH HHS P41 CA196276
6 · The paper itself

Abstract

Probody™ therapeutics are recombinant, proteolytically-activated antibody prodrugs, engineered to remain inert until activated locally by tumor-associated proteases. Probody therapeutics exploit the fundamental dysregulation of extracellular protease activity that exists in tumors relative to healthy tissue. Leveraging the ability of a Probody therapeutic to bind its target at the site of disease after proteolytic cleavage, we developed a novel method for profiling protease activity in living animals. Using NIR optical imaging, we demonstrated that a non-labeled anti-EGFR Probody therapeutic can become activated and compete for binding to tumor cells in vivo with a labeled anti-EGFR monoclonal antibody. Furthermore, by inhibiting matriptase activity in vivo with a blocking-matriptase antibody, we show that the ability of the Probody therapeutic to bind EGFR in vivo was dependent on protease activity. These results demonstrate that in vivo imaging of Probody therapeutic activation can be used for screening and characterization of protease activity in living animals, and provide a method that avoids some of the limitations of prior methods. This approach can improve our understanding of the activity of proteases in disease models and help to develop efficient strategies for cancer diagnosis and treatment.

Indexed as

AnimalsAntibodies, MonoclonalAntineoplastic AgentsBinding, CompetitiveCell Line, TumorCetuximabDiagnostic ImagingErbB ReceptorsFemaleFluorescent DyesHumansLung NeoplasmsMice, NudePeptide HydrolasesProdrugsProtein BindingAlexa Fluor 750Antibodies, MonoclonalAntineoplastic AgentsCetuximabErbB ReceptorsFluorescent DyesPeptide HydrolasesProdrugsSuccinimidesIn vivo imagingMonoclonal antibodyProtease activityTumor targeting

Identifiers

PMID26546838
PMCPMC5709043
OpenAlexW2158096129

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.