{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2023,11,14]],"date-time":"2023-11-14T19:23:08Z","timestamp":1699989788632},"reference-count":29,"publisher":"Wiley","issue":"10","license":[{"start":{"date-parts":[[2006,7,20]],"date-time":"2006-07-20T00:00:00Z","timestamp":1153353600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Intl Journal of Cancer"],"published-print":{"date-parts":[[2006,11,15]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>The epidermal growth factor receptor (EGFR) plays a central role in cell life by controlling processes such as growth or proliferation. This receptor is commonly overexpressed in a number of epithelial malignancies and its upregulation is often associated with an aggressive phenotype of the tumor. Thus, targeting of EGFR represents a very promising challenge in oncology, and antibodies raised against this receptor have been investigated as potential antitumor agents. Various putative mechanisms of action were proposed for such antibodies, including decreased proliferation, induction of apoptosis, stimulation of the immunological response against targeted cancer cells or combinations thereof. We report here the development of an alternative high affinity molecule that is directed against EGFR. Production of this pentameric protein, named peptabody\u2010EGF, includes expression in a bacterial expression system and subsequent refolding and multimerization of peptabody monomers. The protein complex contains 5 human EGF ligand domains, which confer specific binding towards the extracellular portion of EGFR. Receptor binding of the peptabody\u2010EGF had a strong antiproliferative effect on different cancer cell lines overexpressing EGFR. However, cells expressing constitutive levels of the target receptor were barely affected. Peptabody\u2010EGF treated cancer cells exhibited typical characteristics of apoptosis, which was found to be induced within 30 min after the addition of the peptabody\u2010EGF. <jats:italic>In vitro<\/jats:italic> experiments demonstrated a significantly higher binding activity for peptabody\u2010EGF than for the therapeutic monoclonal EGFR antibody Mab\u2010425. Furthermore, the antitumor action provoked by the peptabody\u2010EGF was greatly superior than antibody mediated effects when tested on EGFR overexpressing cancer cell lines. These findings suggest a potential application of this high affinity molecule as a novel tool for anti\u2010EGFR therapy. \u00a9 2006 Wiley\u2010Liss, Inc.<\/jats:p>","DOI":"10.1002\/ijc.21541","type":"journal-article","created":{"date-parts":[[2006,7,20]],"date-time":"2006-07-20T17:49:04Z","timestamp":1153417744000},"page":"2455-2463","source":"Crossref","is-referenced-by-count":4,"title":["Peptabody\u2010EGF: A novel apoptosis inducer targeting ErbB1 receptor overexpressing cancer cells"],"prefix":"10.1002","volume":"119","author":[{"given":"Omar M.","family":"Fattah","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Sylvain M.","family":"Cloutier","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Christoph","family":"K\u00fcndig","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Loyse 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