Targeting the platelet-derived growth factor receptor alpha with a neutralizing human monoclonal antibody inhibits the growth of tumor xenografts: implications as a potential therapeutic target.
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| Abstract |
Platelet-derived growth factor receptor alpha (PDGFRalpha) is a type III receptor tyrosine kinase that is expressed on a variety of tumor types. A neutralizing monoclonal antibody to human PDGFRalpha, which did not cross-react with the beta form of the receptor, was generated. The fully human antibody, termed 3G3, has a Kd of 40 pmol/L and blocks both PDGF-AA and PDGF-BB ligands from binding to PDGFRalpha. In addition to blocking ligand-induced cell mitogenesis and receptor autophosphorylation, 3G3 inhibited phosphorylation of the downstream signaling molecules Akt and mitogen-activated protein kinase. This inhibition was seen in both transfected and tumor cell lines expressing PDGFRalpha. The in vivo antitumor activity of 3G3 was tested in human glioblastoma (U118) and leiomyosarcoma (SKLMS-1) xenograft tumor models in athymic nude mice. Antibody 3G3 significantly inhibited the growth of U118 (P=0.0004) and SKLMS-1 (P <0.0001) tumors relative to control. These data suggest that 3G3 may be useful for the treatment of tumors that express PDGFRalpha.
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| Authors | Nick Loizos, Yan Xu, Jim Huber, Meilin Liu, Dan Lu, Bridget Finnerty, Robin Rolser, Asra Malikzay, Anita Persaud, Erik Corcoran, Dhanvanthri S Deevi, Paul Balderes, Rajiv Bassi, Xenia Jimenez, Christopher J Joynes, Venkata R M Mangalampalli, Philipp Steiner, James R Tonra, Yan Wu, Daniel S Pereira, Zhenping Zhu, Dale L Ludwig, Daniel J Hicklin, Peter Bohlen, Larry Witte, Paul Kussie |
| Journal | Molecular cancer therapeutics (Mol Cancer Ther) Vol. 4 Issue 3 Pg. 369-79 (Mar 2005) ISSN: 1535-7163 [Print] United States |
| PMID | 15767546 (Publication Type: Journal Article) |
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