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|Title:||Characterization of ABT-806, a Humanized Tumor-Specific Anti-EGFR Monoclonal Antibody.||Austin Authors:||Reilly, Edward B;Phillips, Andrew C;Buchanan, Fritz G;Kingsbury, Gillian;Zhang, Yumin;Meulbroek, Jonathan A;Cole, Todd B;DeVries, Peter J;Falls, Hugh D;Beam, Christine;Gu, Jinming;Digiammarino, Enrico L;Palma, Joann P;Donawho, Cherrie K;Goodwin, Neal C;Scott, Andrew M||Affiliation:||Ludwig Institute for Cancer Research, Olivia Newton-John Cancer Research Institute, and La Trobe University, Melbourne, Victoria, Australia
AbbVie, Cancer Discovery, North Chicago, Illinois.
AbbVie Bioresearch Center, Worcester, Massachusetts.
The Jackson Laboratory, Sacramento, California.
|Issue Date:||2-Mar-2015||Publication information:||Molecular Cancer Therapeutics 2015; 14(5): 1141-51||Abstract:||Despite 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.||Gov't Doc #:||25731184||URI:||http://ahro.austin.org.au/austinjspui/handle/1/12664||DOI:||10.1158/1535-7163.MCT-14-0820||Journal:||Molecular cancer therapeutics||URL:||https://pubmed.ncbi.nlm.nih.gov/25731184||Type:||Journal Article|
|Appears in Collections:||Journal articles|
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