Evidence map›Paper›PMID 30278129›Full record

ArticleACS chemical biology2018

Modular Pore-Forming Immunotoxins with Caged Cytotoxicity Tailored by Directed Evolution.

Natalie L Mutter, Misha Soskine, Gang Huang, Inês S Albuquerque, Gonçalo J L Bernardes, Giovanni Maglia

Open access · hybridAbstract read
In one paragraph

Article in ACS chemical biology, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 20 papers.

0numbers the graph read from it
0cells of the map it votes in
20citing papers in PubMed
1.5field-weighted citation impact, top 17% 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

20 citing papers in PubMed, 30 citations in OpenAlex.

  1. Article
  2. Review
  3. Review
  4. Article
  5. Review
  6. Tropical life sciences research · 2022
    Article
  7. Bacterial pore-forming toxins.Microbiology (Reading, England) · 2022
    Article
  8. Article
  9. Review
  10. Cytotoxic effect of sea anemone pore-forming toxin on K562 chronic myeloid leukemia cells.Veterinary research forum : an international quarterly journal · 2021
    Article
  11. Review
  12. Article
  13. Review
  14. Nanobodies: new avenue to treat kidney disease.Cell and tissue research · 2021
    Review
  15. Article
  16. Sea AnemoneMolecules (Basel, Switzerland) · 2020
    Article
  17. Review
  18. Review
  19. Article
  20. Reversible Photocontrolled Nanopore Assembly.Journal of the American Chemical Society · 2019
    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 2 institutions in 3 countries.

Natalie L MutterGroningen Biomolecular Science & Biotechnology Institute , University of Groningen , 9747 AG , Groningen , The Netherlands.ORCID 0000-0002-9144-7443
Misha SoskineGroningen Biomolecular Science & Biotechnology Institute , University of Groningen , 9747 AG , Groningen , The Netherlands.
Gang HuangGroningen Biomolecular Science & Biotechnology Institute , University of Groningen , 9747 AG , Groningen , The Netherlands.
Inês S AlbuquerqueInstituto de Medicina Molecular, Faculdade de Medicina , Universidade de Lisboa , Avenida Professor Egas Moniz , 1649-028 , Lisboa , Portugal.
Gonçalo J L BernardesInstituto de Medicina Molecular, Faculdade de Medicina , Universidade de Lisboa , Avenida Professor Egas Moniz , 1649-028 , Lisboa , Portugal.ORCID 0000-0001-6594-8917
Giovanni MagliaGroningen Biomolecular Science & Biotechnology Institute , University of Groningen , 9747 AG , Groningen , The Netherlands.ORCID 0000-0003-2784-0811
University of Groningen · NLUniversity of Lisbon · PT

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

Immunotoxins are proteins containing a cell-targeting element linked to a toxin that are under investigation for next-generation cancer treatment. However, these agents are difficult to synthesize, chemically heterogeneous, expensive, and show toxicity toward healthy cells. In this work, we describe the synthesis and characterization of a new type of immunotoxin that showed exquisite selectivity toward targeted cells. In our construct, targeting molecules were covalently attached or genetically fused to oligomeric pore-forming toxins. The activity of the immunotoxin was then caged by fusing a soluble protein to the transmembrane domain and activated via cleavage with furin, which is a protease that is overexpressed in many cancer cells. During the several coupling steps, directed evolution allowed the efficient synthesis of the molecules in E. coli cells, as well as selection for further specificity toward targeted cells. The final construct showed no off-target activity, while acquiring an additional degree of specificity toward the targeted cells upon activation. The pore-forming toxins described here do not require internalization to operate, while the many protomeric subunits can be individually modified to refine target specificity.

Indexed as

AnimalsCell Line, TumorCell MembraneCnidarian VenomsDirected Molecular EvolutionDrug DesignEscherichia coliFolic AcidFurinHumansImmunotoxinsMutagenesisPore Forming Cytotoxic ProteinsProteolysisRecombinant Fusion ProteinsSalmonella typhiCnidarian VenomsFolic Acidfragaceatoxin CFurinImmunotoxinsPore Forming Cytotoxic ProteinsRecombinant Fusion ProteinsTetrahydrofolate Dehydrogenase

Identifiers

PMID30278129
PMCPMC6243392
OpenAlexW2894871613

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.