Functional responses and in vivo anti-tumour activity of h7C10: A humanised monoclonal antibody with neutralising activity against the insulin-like growth factor-1 (IGF-1) receptor and insulin/IGF-1 hybrid receptors

Abstract A novel humanised monoclonal antibody (Mab, h7C10) was raised against the human insulin-like growth factor-1 receptor (IGF-1R); it exhibited potent inhibition of tumour growth in animal models. Further evaluation of its inhibitory activity at hybrid receptors (Hybrid-Rs) composed of the ass...

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Bibliographic Details
Published in:European journal of cancer (1990) 2007-05, Vol.43 (8), p.1318-1327
Main Authors: Pandini, Giuseppe, Wurch, Thierry, Akla, Barbara, Corvaia, Nathalie, Belfiore, Antonino, Goetsch, Liliane
Format: Article
Language:English
Subjects:
Animals
Antibodies, Monoclonal - therapeutic use
Biological and medical sciences
Breast Neoplasms - therapy
Down-Regulation
Female
Hematology, Oncology and Palliative Medicine
Humans
Hybrid receptor
IGF-1R
Immunotherapy - methods
Insulin-Like Growth Factor I - immunology
Ligand binding
Medical sciences
Mice
Monoclonal antibody
Mouse xenograft model
Neoplasm Transplantation
Pharmacology. Drug treatments
Phosphorylation
Radioligand Assay
Receptor, IGF Type 1 - immunology
Tumors
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Summary:Abstract A novel humanised monoclonal antibody (Mab, h7C10) was raised against the human insulin-like growth factor-1 receptor (IGF-1R); it exhibited potent inhibition of tumour growth in animal models. Further evaluation of its inhibitory activity at hybrid receptors (Hybrid-Rs) composed of the association between IGF-1R and insulin receptor (IR) was performed. Selective, potent and efficacious inhibition of [125 I]IGF-1 binding as well as IGF-1- and IGF-2-mediated receptor phosphorylation was demonstrated at both IGF-1R and Hybrid-Rs, without activity at IR. Ligand-independent down-regulation of both IGF-1R and Hybrid-Rs was obtained upon long-term association with h7C10. In vivo evaluation was performed in a MDA-MB-231 xenograft mouse model, showing a 14-fold higher level of Hybrid-Rs as compared to IGF-1R. A more potent anti-tumoural response was obtained for h7C10 as compared to Mabs targeting solely IGF-1R or Hybrid-Rs. The herewith described neutralising properties of h7C10 as potent inhibitor of both IGF-1R and Hybrid-Rs are likely to participate in its anti-tumoural activities and maybe of interest for therapeutic applications.
ISSN:0959-8049
1879-0852
DOI:10.1016/j.ejca.2007.03.009