The IGF-trap: novel inhibitor of carcinoma growth and metastasis

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DOIResolve DOI: https://doi.org/10.1158/1535-7163.MCT-14-0751
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Name affiliation
  1. National Research Council of Canada. Human Health Therapeutics
FormatText, Article
Journal titleMolecular Cancer Therapeutics
ISSN1535-7163
1538-8514
Volume14
Issue4
Pages982–993
SubjectIGF; Trap; breast cancer; colon cancer; liver metastasis
Abstract
The IGFI receptor promotes malignant progression and has been recognized as a target for cancer therapy. Clinical trials with anti-IGFIR antibodies provided evidence of therapeutic efficacy but exposed limitations due in part to effects on, and the compensatory function of, the insulin receptor system. Here, we report on the production, characterization, and biologic activity of a novel, IGF-targeting protein (the IGF-Trap) comprising a soluble form of hIGFIR and the Fc portion of hIgG1. The IGF-Trap has a high affinity for hIGFI and hIGFII but low affinity for insulin, as revealed by surface plasmon resonance. It efficiently blocked IGFIR signaling in several carcinoma cell types and inhibited tumor cell proliferation, migration, and invasion in vitro. In vivo, the IGF-Trap showed favorable pharmacokinetic properties and could suppress the growth of established breast carcinoma tumors when administered therapeutically into tumor-bearing mice, improving disease-free survival. Moreover, IGF-Trap treatment markedly reduced experimental liver metastasis of colon and lung carcinoma cells, increasing tumor cell apoptosis and reducing angiogenesis. Finally, when compared with an anti-IGFIR antibody or IGF-binding protein-1 that were used at similar or higher concentrations, the IGF-Trap showed superior therapeutic efficacy to both inhibitors. Taken together, we have developed a targeted therapeutic molecule with highly potent anticancer effects that could address limitations of current IGFIR-targeting agents
Publication date
LanguageEnglish
Peer reviewedYes
NRC numberNRC-HHT-53244
NPARC number21275362
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Record identifier82c3e9ff-bb92-4e4b-a320-669e049fe750
Record created2015-06-16
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