Evidence map›Paper›PMID 31460422›Full record

ArticleACS omega2019

Antibody-Drug Conjugate that Exhibits Synergistic Cytotoxicity with an Endosome-Disruptive Peptide.

Kelsey E Knewtson, Chamani Perera, David Hymel, Zhe Gao, Molly M Lee, Blake R Peterson

Open access · goldAbstract read
In one paragraph

Article in ACS omega, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 5 papers.

0numbers the graph read from it
0cells of the map it votes in
5citing papers in PubMed
2.2field-weighted citation impact, top 12% 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

5 citing papers in PubMed, 15 citations in OpenAlex.

  1. Article
  2. Article
  3. Targeted Fluorogenic Cyanine Carbamates EnableJournal of the American Chemical Society · 2021
    Article
  4. Coiled coil exposure and histidine tags drive function of an intracellular protein drug carrier.Journal of controlled release : official journal of the Controlled Release Society · 2021
    Article
  5. 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

6 authors at 1 institution in 1 country.

Kelsey E KnewtsonDepartment of Medicinal Chemistry, The University of Kansas, Lawrence, Kansas 66045, United States.
Chamani PereraDepartment of Medicinal Chemistry, The University of Kansas, Lawrence, Kansas 66045, United States.
David HymelDepartment of Medicinal Chemistry, The University of Kansas, Lawrence, Kansas 66045, United States.
Zhe GaoDepartment of Medicinal Chemistry, The University of Kansas, Lawrence, Kansas 66045, United States.
Molly M LeeDepartment of Medicinal Chemistry, The University of Kansas, Lawrence, Kansas 66045, United States.
Blake R PetersonDepartment of Medicinal Chemistry, The University of Kansas, Lawrence, Kansas 66045, United States.
University of Kansas · US

Funding

Synthetic Chemical Biology CoreP20GM113117 · NIGMS · UNIVERSITY OF KANSAS LAWRENCE · PI OROZCO, ROBIN C. · 2016 to 2025
$23.9M
Understanding the mechanobiology of stem cells in a microengineered 3D cardiac tissue environment with cardiomyopathyP20GM103638 · NIGMS · UNIVERSITY OF KANSAS LAWRENCE · PI HOLMSTROM, ERIK D · 2012 to 2021
$22.1M
PHARMACEUTICAL ASPECTS OF BIOTECHNOLOGY TRAININGT32GM008359 · NIGMS · UNIVERSITY OF KANSAS LAWRENCE · PI SIAHAAN, TERUNA J., VOLKIN, DAVID · 1989 to 2018
$5.0M
TRAINING GRANT IN DYNAMIC ASPECTS OF CHEMICAL BIOLOGYT32GM008545 · NIGMS · UNIVERSITY OF KANSAS LAWRENCE · PI LAMB, AUDREY L · 1994 to 2019
$4.9M
Synthetic Lethal Targeting of Growth Factor ReceptorsR01CA211720 · NCI · UNIVERSITY OF KANSAS LAWRENCE · PI PETERSON, BLAKE · 2017 to 2021
$1.7M
NCI NIH HHS R01 CA211720NIGMS NIH HHS P20 GM103638NIGMS NIH HHS P20 GM113117NIGMS NIH HHS T32 GM008359NIGMS NIH HHS T32 GM008545
6 · The paper itself

Abstract

Antibody-drug conjugates are an important class of cancer therapeutics. These agents generally bind a specific cell surface receptor, undergo receptor-mediated endocytosis, and enter the endosomal-lysosomal system, where the environment in these organelles facilitates the release of a membrane-permeable cytotoxin. By using a membrane-impermeable cytotoxin, we describe here a method that allows the cytotoxicity of an antibody conjugate to be triggered by co-administration with an endosome-disruptive peptide that exhibits low toxicity. This approach was validated by conjugation of an anionic derivative of the tubulin-binding cytotoxin colchinol methyl ether to lysine residues of the HER2-targeting antibody trastuzumab (Herceptin) via a disulfide. When this antibody binds HER2 on SKBR3 breast cancer cells and undergoes endocytosis, the membrane-impermeable cytotoxin is released, but it becomes trapped in endosomes, resulting in relatively low cytotoxicity (IC

Identifiers

PMID31460422
PMCPMC6690568
OpenAlexW2965336536

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.