Please use this identifier to cite or link to this item: https://ahro.austin.org.au/austinjspui/handle/1/17187
Full metadata record
DC FieldValueLanguage
dc.contributor.authorPhillips, Andrew C-
dc.contributor.authorBoghaert, Erwin R-
dc.contributor.authorVaidya, Kedar S-
dc.contributor.authorFalls, Hugh D-
dc.contributor.authorMitten, Michael J-
dc.contributor.authorDeVries, Peter J-
dc.contributor.authorBenatuil, Lorenzo-
dc.contributor.authorHsieh, Chung-Ming-
dc.contributor.authorMeulbroek, Jonathan A-
dc.contributor.authorPanchal, Sanjay C-
dc.contributor.authorBuchanan, Fritz G-
dc.contributor.authorDurbin, Kenneth R-
dc.contributor.authorVoorbach, Martin J-
dc.contributor.authorReuter, David R-
dc.contributor.authorMudd, Sarah R-
dc.contributor.authorLoberg, Lise I-
dc.contributor.authorRalston, Sherry L-
dc.contributor.authorCao, Diana-
dc.contributor.authorGan, Hui K-
dc.contributor.authorScott, Andrew M-
dc.contributor.authorReilly, Edward B-
dc.date2018-02-26-
dc.date.accessioned2018-03-01T04:12:57Z-
dc.date.available2018-03-01T04:12:57Z-
dc.date.issued2018-02-26-
dc.identifier.citationMolecular cancer therapeutics 2018; 17(4): 795-805-
dc.identifier.urihttps://ahro.austin.org.au/austinjspui/handle/1/17187-
dc.description.abstractDepatuxizumab mafodotin (depatux-m, ABT-414) is a tumor-selective antibody drug conjugate (ADC) comprised of the anti-EGFR antibody ABT-806 and the monomethyl auristatin F (MMAF) warhead. Depatux-m has demonstrated promising clinical activity in glioblastoma multiforme (GBM) patients and is currently being evaluated in clinical trials in first-line and recurrent GBM disease settings. Depatux-m responses have been restricted to patients with amplified EGFR highlighting the need for therapies with activity against tumors with non-amplified EGFR overexpression. Additionally, depatux-m dosing has been limited by corneal side effects common to MMAF conjugates. We hypothesized that a monomethyl auristatin E (MMAE) ADC utilizing an EGFR-targeting antibody with increased affinity may have broader utility against tumors with more modest EGFR overexpression while mitigating the risk of corneal side effects. We describe here preclinical characterization of ABBV-221, an EGFR targeting ADC comprised of an affinity matured ABT-806 conjugated to MMAE. ABBV-221 binds to a similar EGFR epitope as depatux-m and retains tumor selectivity with increased binding to EGFR-positive tumor cells and greater in vitro potency. ABBV-221 displays increased tumor uptake and anti-tumor activity against wild-type EGFR-positive xenografts with a greatly reduced incidence of corneal side effects relative to depatux-m. ABBV-221 has similar activity as depatux-m against an EGFR amplified GBM PDX model and is highly effective alone and in combination with standard of care (SOC) temozolomide in an EGFRvIII positive GBM xenograft model. Based on these results, ABBV-221 has advanced to a phase 1 clinical trial in patients with advanced solid tumors associated with elevated levels of EGFR.-
dc.language.isoeng-
dc.titleCharacterization of ABBV-221, a Tumor-Selective EGFR Targeting Antibody Drug Conjugate.-
dc.typeJournal Article-
dc.identifier.journaltitleMolecular cancer therapeutics-
dc.identifier.affiliationAbbVie Inc-
dc.identifier.affiliationAbbVie Bioresearch Center-
dc.identifier.affiliationBiologics Discovery, Merck Research Laboratories-
dc.identifier.affiliationGlobal Protein Sciences, AbbVie Inc-
dc.identifier.affiliationTranslational Imaging, AbbVie Inc-
dc.identifier.affiliationPreclinical Safety, AbbVie Inc-
dc.identifier.affiliationOlivia Newton-John Cancer Research Institute, Heidelberg, Victoria, Australia-
dc.identifier.doi10.1158/1535-7163.MCT-17-0710-
dc.identifier.orcid0000-0002-6656-295X-
dc.identifier.pubmedid29483208-
dc.type.austinJournal Article-
local.name.researcherGan, Hui K
item.openairecristypehttp://purl.org/coar/resource_type/c_18cf-
item.cerifentitytypePublications-
item.fulltextNo Fulltext-
item.grantfulltextnone-
item.languageiso639-1en-
item.openairetypeJournal Article-
crisitem.author.deptMedical Oncology-
crisitem.author.deptOlivia Newton-John Cancer Wellness and Research Centre-
crisitem.author.deptMolecular Imaging and Therapy-
crisitem.author.deptOlivia Newton-John Cancer Research Institute-
Appears in Collections:Journal articles
Show simple item record

Page view(s)

50
checked on Mar 28, 2024

Google ScholarTM

Check


Items in AHRO are protected by copyright, with all rights reserved, unless otherwise indicated.