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

Eur J Cancer. 2007 May;43(8):1318-27. doi: 10.1016/j.ejca.2007.03.009. Epub 2007 Apr 23.

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.

MeSH terms

  • Animals
  • Antibodies, Monoclonal / therapeutic use*
  • Breast Neoplasms / therapy*
  • Down-Regulation
  • Female
  • Humans
  • Immunotherapy / methods*
  • Insulin-Like Growth Factor I / immunology*
  • Mice
  • Neoplasm Transplantation
  • Phosphorylation
  • Radioligand Assay
  • Receptor, IGF Type 1 / immunology*

Substances

  • Antibodies, Monoclonal
  • Insulin-Like Growth Factor I
  • Receptor, IGF Type 1