A phase I clinical trial with monoclonal antibody ch806 targeting transitional state and mutant epidermal growth factor receptors

• DOI: 10.1073/pnas.0611693104
• Publication Date: 2007-03-01T06:29:21Z
• Authors: Andrew M. Scott; Fook-Thean Lee; Niall Tebbutt; Rebecca Herbertson; Sanjeev S. Gill; Zhanqi Liu; Effie Skrinos; Carmel Murone; Timothy H. Saunder; Bridget Chappell; Anthony T. Papenfuss; Aurora M. T. Poon; Wendie Hopkins; Fiona E. Smyth; Duncan MacGregor; Lawrence M. Cher; Achim A. Jungbluth; Gerd Ritter; Martin W. Brechbiel; Roger Murphy; Antony W. Burgess; Eric W. Hoffman; Terrance G. Johns; Lloyd J. Old
• Keywords: Tumor Antigen

An array of cell-surface antigens expressed by human cancers have been identified as targets for antibody-based therapies. The great majority these antibodies do not specificity cancer but recognize on a range normal cell types (differentiation antigens). Over the past two decades, our group has analyzed thousands mouse monoclonal and battery with limited representation cells. most tumor-specific is 806, an antibody that detects unique epitope epidermal growth factor receptor (EGFR) exposed only overexpressed, mutant, or ligand-activated forms in cancer. In vitro immunohistochemical analysis shows little no detectable 806 reactivity tissues, even those high levels wild-type (wt)EGFR expression. Preclinical studies demonstrated specifically subset EGFR tumor cells, significant anti-tumor effects xenografts, primarily through abrogation signaling pathways. present clinical study was designed to examine vivo chimeric form mAb (ch806) targeting/biodistribution/pharmacokinetic patients diverse types. ch806 showed excellent targeting sites all patients, evidence tissue uptake, toxicity. These characteristics distinguish it from other EGFR.