Evidence map›Paper›PMID 18841159›Full record

ArticleBritish journal of cancer2008

Targeting ErbB2 and ErbB3 with a bispecific single-chain Fv enhances targeting selectivity and induces a therapeutic effect in vitro.

M K Robinson, K M Hodge, E Horak, A L Sundberg, M Russeva, C C Shaller, M von Mehren, I Shchaveleva, H H Simmons, J D Marks and 1 more

Open access · hybridAbstract read
In one paragraph

Article in British journal of cancer, 2008. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 56 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
56citing papers in PubMed, 1 pooled it
4.7field-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

56 citing papers in PubMed, 1 synthesis or guideline pooled it, 128 citations in OpenAlex.

  1. Pooled it
  2. Trial
  3. Article
  4. Review
  5. Article
  6. Article
  7. Article
  8. Article
  9. Article
  10. Article
  11. A quantitative view of strategies to engineer cell-selective ligand binding.Integrative biology : quantitative biosciences from nano to macro · 2021
    Article
  12. HER3 PET Imaging:Cancers · 2021
    Article
  13. Article
  14. PET and SPECT Imaging of the EGFR Family (RTK Class I) in Oncology.International journal of molecular sciences · 2021
    Review
  15. Article
  16. Development of [European journal of nuclear medicine and molecular imaging · 2021
    Article
  17. Article
  18. Article
  19. Increase in negative charge ofScientific reports · 2019
    Article
  20. 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

11 authors at 2 institutions in 1 country.

M K RobinsonDepartment of Medical Oncology, Fox Chase Cancer Center, Philadelphia, PA, USA. mk_robinson@ fccc.edu
K M Hodge
E Horak
A L Sundberg
M Russeva
C C Shaller
M von Mehren
I Shchaveleva
H H Simmons
J D Marks
G P Adams
Fox Chase Cancer Center · USUniversity of California, San Francisco · US

Funding

WORD PROCESSING CENTER--COREP30CA006927 · NCI · RESEARCH INST OF FOX CHASE CAN CTR · PI Margaret von Mehren · 1985 to 2026
$138.8M
NCI NIH HHS P30 CA006927NCI NIH HHS P30CA006927
6 · The paper itself

Abstract

Inappropriate signalling through the EGFR and ErbB2/HER2 members of the epidermal growth factor family of receptor tyrosine kinases is well recognised as being causally linked to a variety of cancers. Consequently, monoclonal antibodies specific for these receptors have become increasingly important components of effective treatment strategies for cancer. Increasing evidence suggests that ErbB3 plays a critical role in cancer progression and resistance to therapy. We hypothesised that co-targeting the preferred ErbB2/ErbB3 heterodimer with a bispecific single-chain Fv (bs-scFv) antibody would promote increased targeting selectivity over antibodies specific for a single tumour-associated antigen (TAA). In addition, we hypothesised that targeting this important heterodimer could induce a therapeutic effect. Here, we describe the construction and evaluation of the A5-linker-ML3.9 bs-scFv (ALM), an anti-ErbB3/ErbB2 bs-scFv. The A5-linker-ML3.9 bs-scFv exhibits selective targeting of tumour cells in vitro and in vivo that co-express the two target antigens over tumour cells that express only one target antigen or normal cells that express low levels of both antigens. The A5-linker-ML3.9 bs-scFv also exhibits significantly greater in vivo targeting of ErbB2'+'/ErbB3'+' tumours than derivative molecules that contain only one functional arm targeting ErbB2 or ErbB3. Binding of ALM to ErbB2'+'/ErbB3'+' cells mediates inhibition of tumour cell growth in vitro by effectively targeting the therapeutic anti-ErbB3 A5 scFv. This suggests both that ALM could provide the basis for an effective therapeutic agent and that engineered antibodies selected to co-target critical functional pairs of TAAs can enhance the targeting specificity and efficacy of antibody-based cancer therapeutics.

Indexed as

AnimalsAntibodies, BispecificAntigens, NeoplasmCell Line, TumorDimerizationErb-b2 Receptor Tyrosine KinasesHumansImmunoglobulin Fc FragmentsMaleMiceMice, Inbred ICRNeoplasmsReceptor, ErbB-3Antibodies, BispecificAntigens, NeoplasmERBB2 protein, humanErb-b2 Receptor Tyrosine KinasesImmunoglobulin Fc FragmentsReceptor, ErbB-3

Identifiers

PMID18841159
PMCPMC2576487
OpenAlexW2059769719

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.