Development of ABX-EGF, a fully human anti-EGF receptor monoclonal antibody, for cancer therapy
Section snippets
Evolution of monoclonal antibody technology
With the development of hybridoma technology by Kohler and Milstein more than 25 years ago, the potential of monoclonal antibodies (mAbs) for human therapy was easily appreciated [1]. However, the promise of the ‘magic bullet’ was not immediately realized since the first generation of mAbs was derived from mouse and the mouse mAbs were in general immunogenic in humans leading to the generation of human anti-mouse antibody (HAMA) responses, thus limiting efficacy in long term and repeated
EGFr overexpression on human tumors
Various growth factors and growth factor receptors have been implicated in a wide variety of human cancers. EGF is a mitogenic hormone that regulates the proliferation and differentiation of normal and neoplastic cells in vitro as well as in vivo. Production of TGF-α, an EGF-related polypeptide growth factor, has been associated with cellular transformation. The EGFr, which binds both EGF and TGF-α, is structurally related to the transforming protein encoded by the v-erbB oncogene of avian
Conclusion
XenoMouse technology has been proven to be a useful tool to develop human therapeutic mAbs for the treatment of variety of diseases, including cancer and inflammatory diseases [21], [24]. The XenoMouse-derived fully human anti-EGFr mAb, ABX-EGF, demonstrated potent anti-tumor activity as a monotherapeutic agent in a variety of human carcinoma xenografts that overexpress EGFr. The observation that tumor growth inhibition by ABX-EGF is dependent on EGFr number suggests that the growth of EGFr
Reviewers
This article was reviewed by Dr Robert B. Cohen, Division of Hematology/Oncology, Box 800716, University of Virginia Health System, Charlottesville, VA 22908, USA; Shimon Slavin, MD, Cancer Immunotherapy Research Center, Hadassah University Hospital, Jerusalem 91120, Israel; Gerd Ritter, Ph.D., Associate Member, Lundwig Institute for Cancer Research, New York Branch @ MSKCC, 1275 York Avenue, New York, NY 10021, USA.
Xiao-Dong Yang is Senior Scientist and the head of the Preclinical Biology Division at Abgenix, Inc.
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Xiao-Dong Yang is Senior Scientist and the head of the Preclinical Biology Division at Abgenix, Inc.