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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.identifier.citationPharmaceuticals 2020; 13(10); 289en
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.subjectmalignant mesotheliomaen
dc.titleTargeting and Efficacy of Novel mAb806-Antibody-Drug Conjugates in Malignant Mesothelioma.en
dc.typeJournal Articleen
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.pubmedid33023139, Puey Ling
item.fulltextNo Fulltext-
item.openairetypeJournal Article- Newton-John Cancer Research Institute- Oncology- Oncology- Newton-John Cancer Wellness and Research Centre- Newton-John Cancer Research Institute- Oncology- Newton-John Cancer Wellness and Research Centre- Imaging and Therapy- Newton-John Cancer Research Institute-
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