Journal article
A truncated soluble epidermal growth factor receptor-Fc fusion ligand trap displays anti-tumour activity in vivo
T Adams, EJ Koziolek, PH Hoyne, JD Bentley, L Lu, G Lovrecz, CW Ward, FT Lee, AM Scott, AD Nash, J Rothacker, EC Nice, AW Burgess, TG Johns
Growth Factors | TAYLOR & FRANCIS LTD | Published : 2009
Abstract
A number of therapeutic strategies including small molecule tyrosine kinase inhibitors and monoclonal antibodies have been developed to target the epidermal growth factor receptor (EGFR) signalling axis for the treatment of cancer. To date, the focus of therapeutic intervention has been the EGFR itself. In the current study, we have assembled and expressed in mammalian cells a soluble, EGFR ligand trap comprising the first 501 amino acids of the mature EGFR sequence fused in-frame with a human IgG Fc domain. The fusion protein, designated sEGFR501.Fc, was secreted as a 220 kDa disulphide-linked homodimer that exhibited high affinity (0.4-8-nM) in competition assays for a number of EGFR ligan..
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Funding Acknowledgements
We would like to thank Dr Mike Shepherd (Receptor Biologix) for sharing information prior to publication, and Dr Neil McKern for advice with protein purification. This work was supported in part by the Australian government through the CRC program, and by grants from Zenyth Pharmaceuticals and the NH& MRC of Australia (Project Grant No. 433615).