Evidence map›Paper›PMID 23675426›Full record

ArticlePloS one2013

Inhibiting HER3-mediated tumor cell growth with affibody molecules engineered to low picomolar affinity by position-directed error-prone PCR-like diversification.

Magdalena Malm, Nina Kronqvist, Hanna Lindberg, Lindvi Gudmundsdotter, Tarek Bass, Fredrik Y Frejd, Ingmarie Höidén-Guthenberg, Zohreh Varasteh, Anna Orlova, Vladimir Tolmachev and 2 more

Erratum issuedOpen access · goldAbstract read
In one paragraph

Article in PloS one, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. An erratum has been issued. Cited by 39 papers.

0numbers the graph read from it
0cells of the map it votes in
39citing papers in PubMed
5.8field-weighted citation impact, top 4% 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

39 citing papers in PubMed, 73 citations in OpenAlex.

  1. Article
  2. Article
  3. Article
  4. Review
  5. Article
  6. Bacterial Cell Display for Selection of Affibody Molecules.Methods in molecular biology (Clifton, N.J.) · 2023
    Review
  7. Article
  8. Article
  9. Article
  10. HER3 PET Imaging:Cancers · 2021
    Article
  11. Article
  12. Article
  13. Article
  14. The Radiolabeled HER3 Targeting Molecules for Tumor Imaging.Iranian journal of pharmaceutical research : IJPR · 2021
    Review
  15. Article
  16. Article
  17. Review
  18. Article
  19. Article
  20. Article
4 · The record

Corrections and comments

  • Erratum issued
5 · Who and what money

Authors and funding

12 authors at 3 institutions in 1 country.

Magdalena MalmDivision of Protein Technology, School of Biotechnology, KTH Royal Institute of Technology, Stockholm, Sweden.
Nina Kronqvist
Hanna Lindberg
Lindvi Gudmundsdotter
Tarek Bass
Fredrik Y Frejd
Ingmarie Höidén-Guthenberg
Zohreh Varasteh
Anna Orlova
Vladimir Tolmachev
Stefan Ståhl
John Löfblom
KTH Royal Institute of Technology · SEUppsala University · SEAffibody (Sweden) · SE

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

The HER3 receptor is implicated in the progression of various cancers as well as in resistance to several currently used drugs, and is hence a potential target for development of new therapies. We have previously generated Affibody molecules that inhibit heregulin-induced signaling of the HER3 pathways. The aim of this study was to improve the affinity of the binders to hopefully increase receptor inhibition efficacy and enable a high receptor-mediated uptake in tumors. We explored a novel strategy for affinity maturation of Affibody molecules that is based on alanine scanning followed by design of library diversification to mimic the result from an error-prone PCR reaction, but with full control over mutated positions and thus less biases. Using bacterial surface display and flow-cytometric sorting of the maturation library, the affinity for HER3 was improved more than 30-fold down to 21 pM. The affinity is among the higher that has been reported for Affibody molecules and we believe that the maturation strategy should be generally applicable for improvement of affinity proteins. The new binders also demonstrated an improved thermal stability as well as complete refolding after denaturation. Moreover, inhibition of ligand-induced proliferation of HER3-positive breast cancer cells was improved more than two orders of magnitude compared to the previously best-performing clone. Radiolabeled Affibody molecules showed specific targeting of a number of HER3-positive cell lines in vitro as well as targeting of HER3 in in vivo mouse models and represent promising candidates for future development of targeted therapies and diagnostics.

Indexed as

AlanineAnimalsBiosensing TechniquesCell Line, TumorCell ProliferationCell Surface Display TechniquesCircular DichroismFemaleHumansInhibitory Concentration 50LigandsMiceMutationNeoplasmsPeptide LibraryPhosphorylationAlanineLigandsPeptide LibraryReceptor, ErbB-3Recombinant Fusion Proteins

Identifiers

PMID23675426
PMCPMC3651084
OpenAlexW2127797287

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.