PEDS Advance Access originally published online on June 18, 2004
Protein Engineering Design and Selection 2004 17(5):455-462; doi:10.1093/protein/gzh053
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Selection and characterization of HER2/neu-binding affibody ligands
1Department of Biotechnology, AlbaNova University Center, Kungl Tekniska Högskolan (KTH), SE-106 91 Stockholm, 2Department of Oncology, Radiology and Clinical Immunology, Rudbeck Laboratory, Uppsala University, SE-751 85 Uppsala, 3Affibody AB, PO Box 20137, SE-161 02 Bromma, Sweden and 4Department of Medical Oncology, Fox Chase Cancer Center, Philadelphia, PA 19111, USA
5 To whom correspondence should be addressed. E-mail: stefans{at}biotech.kth.se
Affibody® (affibody) ligands that are specific for the extracellular domain of human epidermal growth factor receptor 2 (HER2/neu) have been selected by phage display technology from a combinatorial protein library based on the 58 amino acid residue staphylococcal protein A-derived Z domain. The predominant variants from the phage selection were produced in Escherichia coli, purified by affinity chromatography, and characterized by biosensor analyses. Two affibody variants were shown to selectively bind to the extracellular domain of HER2/neu (HER2-ECD), but not to control proteins. One of the variants, denoted His6-ZHER2/neu:4, was demonstrated to bind with nanomolar affinity (
50 nM) to the HER2-ECD molecule at a different site than the monoclonal antibody trastuzumab. Furthermore, radiolabeled His6-ZHER2/neu:4 affibody showed specific binding to native HER2/neu, overexpressed on the SKBR-3 tumor cell line. Such affibody ligands might be considered in tumor targeting applications for radionuclide diagnostics and therapy of adenocarcinomas such as breast and ovarian cancers.
Received March 10, 2004; revised May 17, 2004; accepted May 26, 2004.
Edited by Mathias Uhlen
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