Evidence map›Paper›PMID 27463727›Full record

ArticleToxins2016

Protection of the Furin Cleavage Site in Low-Toxicity Immunotoxins Based on Pseudomonas Exotoxin A.

Gilad Kaplan, Fred Lee, Masanori Onda, Emily Kolyvas, Gaurav Bhardwaj, David Baker, Ira Pastan

Open access · goldAbstract readComparative Study
In one paragraph

Article in Toxins, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 16 papers.

0numbers the graph read from it
0cells of the map it votes in
16citing papers in PubMed
1.2field-weighted citation impact, top 21% 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

16 citing papers in PubMed, 30 citations in OpenAlex.

  1. Taming Bacterial Toxins into an Anticancer Platform.Biochemical and biophysical research communications · 2025
    Article
  2. Article
  3. Antibody-drug conjugates: Recent advances in payloads.Acta pharmaceutica Sinica. B · 2023
    Review
  4. Article
  5. Review
  6. Review
  7. Frontiers in oncology · 2021
    Review
  8. Antibody-Drug Conjugates: The New Frontier of Chemotherapy.International journal of molecular sciences · 2020
    Review
  9. Review
  10. Review
  11. Article
  12. Review
  13. Improving theMolecular cancer therapeutics · 2018
    Article
  14. Domain II ofToxins · 2018
    Article
  15. Recombinant immunotoxins with albumin-binding domains have long half-lives and high antitumor activity.Proceedings of the National Academy of Sciences of the United States of America · 2018
    Article
  16. 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

7 authors at 4 institutions in 1 country.

Gilad KaplanLaboratory of Molecular Biology, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892, USA. gilad.kaplan@nih.gov.
Fred LeeLaboratory of Molecular Biology, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892, USA. fred.lee@nih.gov.
Masanori OndaLaboratory of Molecular Biology, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892, USA. OndaM@mail.nih.gov.
Emily KolyvasLaboratory of Molecular Biology, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892, USA. emily.kolyvas@nih.gov.
Gaurav BhardwajDepartment of Biochemistry, University of Washington, Seattle, WA 98195, USA. Gauravb@uw.edu.
David BakerDepartment of Biochemistry, University of Washington, Seattle, WA 98195, USA. dabaker@uw.edu.
Ira PastanLaboratory of Molecular Biology, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892, USA. pastani@mail.nih.gov.
National Cancer Institute · USNational Institutes of Health · USUniversity of Washington · USCenter for Cancer Research · US

Funding

Immunotoxin Therapy of Solid and Hematopoietic Tumors: Preclinical StudiesZIABC008753 · NCI · DIVISION OF BASIC SCIENCES - NCI · PI PASTAN, IRA · 2009 to 2024
$33.1M
Howard Hughes Medical Institute
6 · The paper itself

Abstract

Recombinant immunotoxins (RITs) are fusions of an Fv-based targeting moiety and a toxin. Pseudomonas exotoxin A (PE) has been used to make several immunotoxins that have been evaluated in clinical trials. Immunogenicity of the bacterial toxin and off-target toxicity have limited the efficacy of these immunotoxins. To address these issues, we have previously made RITs in which the Fv is connected to domain III (PE24) by a furin cleavage site (FCS), thereby removing unneeded sequences of domain II. However, the PE24 containing RITs do not contain the naturally occurring disulfide bond around the furin cleavage sequence, because it was removed when domain II was deleted. This could potentially allow PE24 containing immunotoxins to be cleaved and inactivated before internalization by cell surface furin or other proteases in the blood stream or tumor microenvironment. Here, we describe five new RITs in which a disulfide bond is engineered to protect the FCS. The most active of these, SS1-Fab-DS3-PE24, shows a longer serum half-life than an RIT without the disulfide bond and has the same anti-tumor activity, despite being less cytotoxic in vitro. These results have significance for the production of de-immunized, low toxicity, PE24-based immunotoxins with a longer serum half-life.

Indexed as

Drug DesignADP Ribose TransferasesAnimalsBacterial ToxinsCell Line, TumorCell ProliferationDisulfidesDose-Response Relationship, DrugDrug StabilityExotoxinsFurinHalf-LifeHumansImmunoglobulin Variable RegionImmunotoxinsInhibitory Concentration 50ADP Ribose TransferasesBacterial ToxinsDisulfidesExotoxinsFurinImmunoglobulin Variable RegionImmunotoxinsMesothelinMsln protein, mousePseudomonas aeruginosa Exotoxin ARecombinant ProteinsVirulence Factorsdisulfide bondmesothelinPseudomonas exotoxin Arecombinant immunotoxin

Identifiers

PMID27463727
PMCPMC4999843
OpenAlexW2491001938

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.