Selection of affibody molecules to the ligand-binding site of the insulin-like growth factor-1 receptor

Biotechnol Appl Biochem. 2010 Feb 25;55(2):99-109. doi: 10.1042/BA20090226.

Abstract

Affibody molecules binding to the site of hormone interaction in IGF-1R (insulin-like growth factor-1 receptor) were successfully selected by phage-display technology employing a competitive-elution strategy during biopanning, whereby release of receptor-bound phagemids was accomplished by competition with IGF-1 (insulin-like growth factor-1). In non-competitive selections, the elution of receptor-bound phagemids was performed by imidazole or low-pH incubation, which also resulted in the isolation of affibody molecules that could bind to the receptor. An ELISA-based assay showed that the affibody molecules generated by IGF-1 competition during elution, in addition to affibody molecules generated in the non-competitive selections, could compete with IGF-1 for binding to the receptor. The affinities of the isolated variants to IGF-1R-overexpressing MCF-7 cells were determined and ranged from high nanomolar to 2.3 nM. The most promising variant, Z4:40, was shown to recognize IGF-1R efficiently in several different contexts: in analyses based on flow cytometry, fluorescence microscopy and receptor pull-down from cell extracts. In addition, when Z4:40 was added to the medium of MCF-7 cells that were dependent on IGF-1 for efficient growth, it was found to have a dose-dependent growth-inhibitory effect on the cells. Applications of affibody-based reagents for quantitative and qualitative analyses of IGF-1R status, as well as applications of affibody-based reagents for therapy, are discussed.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antibodies, Monoclonal / chemistry*
  • Antibodies, Monoclonal / genetics
  • Antibodies, Monoclonal / immunology
  • Cell Line, Tumor
  • Enzyme-Linked Immunosorbent Assay
  • Humans
  • Mice
  • Receptor, IGF Type 1 / chemistry*
  • Receptor, IGF Type 1 / immunology
  • Single-Chain Antibodies / chemistry*
  • Single-Chain Antibodies / genetics
  • Single-Chain Antibodies / immunology

Substances

  • Antibodies, Monoclonal
  • Single-Chain Antibodies
  • Receptor, IGF Type 1