Evidence map›Paper›PMID 30247737›Full record

ArticleProtein engineering, design & selection : PEDS2018

Adnectin-drug conjugates for Glypican-3-specific delivery of a cytotoxic payload to tumors.

Daša Lipovšek, Irvith Carvajal, Alban J Allentoff, Anthony Barros, John Brailsford, Qiang Cong, Pete Cotter, Sanjeev Gangwar, Cris Hollander, Virginie Lafont and 13 more

Open access · bronzeAbstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Protein engineering, design & selection : PEDS, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 15 papers.

0numbers the graph read from it
0cells of the map it votes in
15citing papers in PubMed
2.7field-weighted citation impact, top 9% 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

15 citing papers in PubMed, 23 citations in OpenAlex.

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  12. The Role of Glypicans in Cancer Progression and Therapy.The journal of histochemistry and cytochemistry : official journal of the Histochemistry Society · 2020
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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

23 authors at 1 institution in 1 country.

Daša LipovšekMolecular Discovery Technologies, Bristol-Myers Squibb, Waltham, MA, USA.
Irvith CarvajalMolecular Discovery Technologies, Bristol-Myers Squibb, Waltham, MA, USA.
Alban J AllentoffRadiochemistry, Bristol-Myers Squibb, Lawrenceville, NJ, USA.
Anthony BarrosPreclinical Candidate Optimization, Bristol-Myers Squibb, Lawrenceville, NJ, USA.
John BrailsfordRadiochemistry, Bristol-Myers Squibb, Lawrenceville, NJ, USA.
Qiang CongDiscovery Chemistry Oncology, Bristol-Myers Squibb, Redwood City, CA, USA.
Pete CotterMolecular Discovery Technologies, Bristol-Myers Squibb, Waltham, MA, USA.
Sanjeev GangwarDiscovery Chemistry Oncology, Bristol-Myers Squibb, Redwood City, CA, USA.
Cris HollanderMolecular Discovery Technologies, Bristol-Myers Squibb, Waltham, MA, USA.
Virginie LafontMolecular Discovery Technologies, Bristol-Myers Squibb, Lawrenceville, NJ, USA.
Wai Leung LauMolecular Discovery Technologies, Bristol-Myers Squibb, Waltham, MA, USA.
Wenying LiPreclinical Candidate Optimization, Bristol-Myers Squibb, Lawrenceville, NJ, USA.
Miguel MoretaMolecular Discovery Technologies, Bristol-Myers Squibb, Waltham, MA, USA.
Steven O'NeilMolecular Discovery Technologies, Bristol-Myers Squibb, Waltham, MA, USA.
Jason PinckneyMolecular Discovery Technologies, Bristol-Myers Squibb, Waltham, MA, USA.
Michael J SmithChemical and Synthetic Development, Bristol-Myers Squibb, New Brunswick, NJ, USA.
Julie SuMolecular Discovery Technologies, Bristol-Myers Squibb, Waltham, MA, USA.
Christina TerragniMolecular Discovery Technologies, Bristol-Myers Squibb, Waltham, MA, USA.
Michael A WallaceRadiochemistry, Bristol-Myers Squibb, Lawrenceville, NJ, USA.
Lifei WangPreclinical Candidate Optimization, Bristol-Myers Squibb, Lawrenceville, NJ, USA.
Martin WrightMolecular Discovery Technologies, Bristol-Myers Squibb, Waltham, MA, USA.
H Nicholas MarshMolecular Discovery Technologies, Bristol-Myers Squibb, Waltham, MA, USA.
James W BrysonMolecular Discovery Technologies, Bristol-Myers Squibb, Waltham, MA, USA.
Bristol-Myers Squibb (United States) · US

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

Tumor-specific delivery of cytotoxic agents remains a challenge in cancer therapy. Antibody-drug conjugates (ADC) deliver their payloads to tumor cells that overexpress specific tumor-associated antigens-but the multi-day half-life of ADC leads to high exposure even of normal, antigen-free, tissues and thus contributes to dose-limiting toxicity. Here, we present Adnectin-drug conjugates, an alternative platform for tumor-specific delivery of cytotoxic payloads. Due to their small size (10 kDa), renal filtration eliminates Adnectins from the bloodstream within minutes to hours, ensuring low exposure to normal tissues. We used an engineered cysteine to conjugate an Adnectin that binds Glypican-3, a membrane protein overexpressed in hepatocellular carcinoma, to a cytotoxic derivative of tubulysin, with the drug-to-Adnectin ratio of 1. We demonstrate specific, nanomolar binding of this Adnectin-drug conjugate to human and murine Glypican-3; its high thermostability; its localization to target-expressing tumor cells in vitro and in vivo, its fast clearance from normal tissues and its efficacy against Glypican-3-positive mouse xenograft models.

Indexed as

Amino Acid SequenceAnimalsDrug StabilityFemaleGlypicansHEK293 CellsHumansImmunoconjugatesMiceNeoplasmsTissue DistributionGlypicansImmunoconjugates

Identifiers

PMID30247737
PMCPMC6158766
OpenAlexW2808760242

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.