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dc.contributor.authorReilly, Edward Ben
dc.contributor.authorPhillips, Andrew Cen
dc.contributor.authorBuchanan, Fritz Gen
dc.contributor.authorKingsbury, Gillianen
dc.contributor.authorZhang, Yuminen
dc.contributor.authorMeulbroek, Jonathan Aen
dc.contributor.authorCole, Todd Ben
dc.contributor.authorDeVries, Peter Jen
dc.contributor.authorFalls, Hugh Den
dc.contributor.authorBeam, Christineen
dc.contributor.authorGu, Jinmingen
dc.contributor.authorDigiammarino, Enrico Len
dc.contributor.authorPalma, Joann Pen
dc.contributor.authorDonawho, Cherrie Ken
dc.contributor.authorGoodwin, Neal Cen
dc.contributor.authorScott, Andrew Men
dc.date.accessioned2015-05-16T02:23:29Z
dc.date.available2015-05-16T02:23:29Z
dc.date.issued2015-03-02en
dc.identifier.citationMolecular Cancer Therapeutics 2015; 14(5): 1141-51en
dc.identifier.govdoc25731184en
dc.identifier.otherPUBMEDen
dc.identifier.urihttp://ahro.austin.org.au/austinjspui/handle/1/12664en
dc.description.abstractDespite clinical efficacy, current approved agents targeting EGFR are associated with on-target toxicities as a consequence of disrupting normal EGFR function. MAb 806 is a novel EGFR antibody that selectively targets a tumor-selective epitope suggesting that a mAb 806-based therapeutic would retain antitumor activity without the on-target toxicities associated with EGFR inhibition. To enable clinical development, a humanized variant of mAb 806 designated ABT-806 was generated and is currently in phase 1 trials. We describe the characterization of binding and functional properties of ABT-806 compared with the clinically validated anti-EGFR antibody cetuximab. ABT-806 binds the mutant EGFRvIII with high affinity and, relative to cetuximab, exhibits increased potency against glioblastoma multiforme cell line and patient-derived xenografts expressing this form of the receptor. ABT-806 also inhibits the growth of squamous cell carcinoma xenograft models expressing high levels of wild-type EGFR, associated with inhibition of EGFR signaling, although higher doses of ABT-806 than cetuximab are required for similar activity. ABT-806 enhances in vivo potency of standard-of-care therapies used to treat glioblastoma multiforme and head and neck squamous cell carcinoma. An indium-labeled version of ABT-806, [(111)In]-ABT-806, used to investigate the relationship between dose and receptor occupancy, revealed greater receptor occupancy at lowers doses in an EGFRvIII-expressing model and significant uptake in an orthotopic model. Collectively, these results suggest that ABT-806 may have antitumor activity superior to cetuximab in EGFRvIII-expressing tumors, and similar activity to cetuximab in tumors highly overexpressing wild-type EGFR with reduced toxicity. Mol Cancer Ther; 14(5); 1141-51. ©2015 AACR.en
dc.language.isoenen
dc.titleCharacterization of ABT-806, a Humanized Tumor-Specific Anti-EGFR Monoclonal Antibody.en
dc.typeJournal Articleen
dc.identifier.journaltitleMolecular cancer therapeuticsen
dc.identifier.affiliationLudwig Institute for Cancer Research, Olivia Newton-John Cancer Research Institute, and La Trobe University, Melbourne, Victoria, Australiaen
dc.identifier.affiliationAbbVie, Cancer Discovery, North Chicago, Illinois. ed.reilly@abbvie.com.en
dc.identifier.affiliationAbbVie, Cancer Discovery, North Chicago, Illinois.en
dc.identifier.affiliationAbbVie Bioresearch Center, Worcester, Massachusetts.en
dc.identifier.affiliationThe Jackson Laboratory, Sacramento, California.en
dc.identifier.doi10.1158/1535-7163.MCT-14-0820en
dc.description.pages1141-51en
dc.relation.urlhttp://www.ncbi.nlm.nih.gov/pubmed/25731184en
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