Therapeutic potential of ABX-EGF: a fully human anti-epidermal growth factor receptor monoclonal antibody for cancer treatment.
Overexpression of the epidermal growth factor receptor (EGFR) has been observed in a wide variety of human cancers and is associated with a poor clinical prognosis. In many cases, growth of the tumor cells is dependent on EGFR-mediated signals, because inhibition of binding of factors to the EGFR leads to cell death. Using XenoMouse technology, a fully human EGFR-specific monoclonal antibody, ABX-EGF, with high affinity (5 x 10(-11) mol/L) has been generated. ABX-EGF blocks binding of both epidermal growth factor and transforming growth factor alpha to the EGFR, inhibits tyrosine phosphorylation of the EGFR, and inhibits cellular proliferation. In vivo, ABX-EGF not only blocks formation of human epidermoid carcinoma A431 xenografts in athymic mice, but also mediates therapeutic elimination of established tumors and acts cooperatively with chemotherapeutics in mediating tumor regression. These observations provide a strong basis for the development of ABX-EGF as a therapeutic agent for human solid tumors that overexpress EGFR.
Lynch
David H
DH
Department of Cancer Biology, Immunex Corporation, Seattle, WA 98101, USA.
Yang
Xiao-Dong
XD
D000818:Animals; D000911:Antibodies, Monoclonal / Q000494:pharmacology*; D000970:Antineoplastic Agents / Q000494:pharmacology*; D017209:Apoptosis; D066246:ErbB Receptors / Q000096:biosynthesis / Q000187:drug effects*; D006801:Humans; D051379:Mice; D008819:Mice, Nude; D009369:Neoplasms / Q000188:drug therapy; D009374:Neoplasms, Experimental; D000077544:Panitumumab; D010766:Phosphorylation; D011379:Prognosis; D015398:Signal Transduction / Q000187:drug effects; D014183:Transplantation, Heterologous; D014443:Tyrosine / Q000378:metabolism; D015854:Up-Regulation
D000911:Antibodies, Monoclonal; D000970:Antineoplastic Agents; D014443:Tyrosine; D000077544:Panitumumab; D066246:ErbB Receptors