Journal article
Antibodies specifically targeting a locally misfolded region of tumor associated EGFR
TPJ Garrett, AW Burgess, HK Gan, RB Luwor, G Cartwright, F Walker, SG Orchard, AHA Clayton, EC Nice, J Rothacker, B Catimel, WK Cavenee, LJ Old, E Stockert, G Ritter, TE Adams, PA Hoyne, D Wittrup, G Chao, JR Cochran Show all
Proceedings of the National Academy of Sciences of the United States of America | Published : 2009
Abstract
Epidermal Growth Factor Receptor (EGFR) is involved in stimulating the growth of many human tumors, but the success of therapeutic agents has been limited in part by interference from the EGFR on normal tissues. Previously, we reported an antibody (mab806) against a truncated form of EGFR found commonly in gliomas. Remarkably, it also recognizes full-length EGFR on tumor cells but not on normal cells. However, the mechanism for this activity was unclear. Crystallographic structures for Fab:EGFR287-302 complexes of mAb806 (and a second, related antibody, mAb175) show that this peptide epitope adopts conformations similar to those found in the wtEGFR. However, in both conformations observed fo..
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Awarded by National Cancer Institute
Funding Acknowledgements
We thank Colin Ward for valuable advice; Peter Czabotar, Marc Kvansakul, and Peter Colman for collecting some data at the National Synchrotron Light Source (NSLS), Upton, NY; the staff at beamline X29 for their assistance; and the Australian Synchrotron Research Program and the U.S. Department of Energy for providing access. This work was supported in part by National Health and Medical Research Council Program Grant 280912 and Project Grant 433615 and National Institutes of Health Grant CA96504. W.D.F. and T.P.J.G. are supported by National Health and Medical Research Council Fellowships. W.K.C. is supported in part by National Cancer Institute-National Institutes of Health Grant CA95616 and is a fellow of the National Foundation for Cancer Research.