Please use this identifier to cite or link to this item: https://ahro.austin.org.au/austinjspui/handle/1/25057
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dc.contributor.authorChia, Puey Ling-
dc.contributor.authorParakh, Sagun-
dc.contributor.authorTsao, Ming-Sound-
dc.contributor.authorPham, Nhu-An-
dc.contributor.authorGan, Hui K-
dc.contributor.authorCao, Diana-
dc.contributor.authorBurvenich, Ingrid J G-
dc.contributor.authorRigopoulos, Angela-
dc.contributor.authorReilly, Edward B-
dc.contributor.authorJohn, Thomas-
dc.contributor.authorScott, Andrew M-
dc.date2020-10-02-
dc.date.accessioned2020-10-15T03:16:45Z-
dc.date.available2020-10-15T03:16:45Z-
dc.date.issued2020-10-02-
dc.identifier.citationPharmaceuticals 2020; 13(10); 289en
dc.identifier.issn1424-8247
dc.identifier.urihttps://ahro.austin.org.au/austinjspui/handle/1/25057-
dc.description.abstractEpidermal growth factor receptor (EGFR) is highly overexpressed in malignant mesothelioma (MM). MAb806 is a novel anti-EGFR antibody that selectively targets a tumor-selective epitope. MAb806-derived antibody drug conjugates (ADCs), ABT-414, ABBV-221 and ABBV-322, may represent a novel therapeutic strategy in MM. EGFR and mAb806 epitope expressions in mesothelioma cell lines were evaluated using an array of binding assays, and the in vitro cell effects of ABT-414 and ABBV-322 were determined. In vivo therapy studies were conducted in mesothelioma xenograft and patient-derived xenograft (PDX) tumor models. We also performed biodistribution and imaging studies to allow the quantitative targeting of MM by mAb806 using a 89Zr-labeled immunoconjugate-ch806. A high EGFR expression was present in all mesothelioma cell lines evaluated and mAb806 binding present in all cell lines, except NCIH-2452. ABT-414 and ABBV-322 resulted in significant tumor growth inhibition in MM models with high EGFR and mAb806 epitope expressions. In contrast, in an EGFR-expressing PDX model that was negative for the mAb806 epitope, no growth inhibition was observed. We demonstrated the specific targeting of the mAb806 epitope expressing MM tumors using 89Zr-based PET imaging. Our data suggest that targeting EGFR in MM using specific ADCs is a valid therapeutic strategy and supports further investigation of the mAb806 epitope expression as a predictive biomarker.en
dc.language.isoeng
dc.subject806-ADCen
dc.subject89Zr-ch806en
dc.subjectEGFRen
dc.subjectmalignant mesotheliomaen
dc.titleTargeting and Efficacy of Novel mAb806-Antibody-Drug Conjugates in Malignant Mesothelioma.en
dc.typeJournal Articleen
dc.identifier.journaltitlePharmaceuticalsen
dc.identifier.affiliationOlivia Newton-John Cancer Research Instituteen
dc.identifier.affiliationPrincess Margaret Cancer Centre, University Health Network, Toronto, ON M5G 2C1, Canadaen
dc.identifier.affiliationMedical Oncologyen
dc.identifier.affiliationSchool of Cancer Medicine, La Trobe University, Plenty Rd &, Kingsbury Dr, Bundoora, Victoria 3086, Australiaen
dc.identifier.affiliationFaculty of Medicine, University of Melbourne, Melbourne, Victoria 3010, Australiaen
dc.identifier.affiliationMolecular Imaging and Therapyen
dc.identifier.affiliationAbbVie Inc., North Chicago, IL 60064, USAen
dc.identifier.doi10.3390/ph13100289en
dc.type.contentTexten
dc.identifier.orcid0000-0002-9160-5405en
dc.identifier.orcid0000-0001-8384-2403en
dc.identifier.pubmedid33023139
local.name.researcherChia, Puey Ling
item.fulltextNo Fulltext-
item.openairecristypehttp://purl.org/coar/resource_type/c_18cf-
item.cerifentitytypePublications-
item.languageiso639-1en-
item.grantfulltextnone-
item.openairetypeJournal Article-
crisitem.author.deptOlivia Newton-John Cancer Research Institute-
crisitem.author.deptMedical Oncology-
crisitem.author.deptMedical Oncology-
crisitem.author.deptOlivia Newton-John Cancer Wellness and Research Centre-
crisitem.author.deptOlivia Newton-John Cancer Research Institute-
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-
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