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Title: Targeting and Efficacy of Novel mAb806-Antibody-Drug Conjugates in Malignant Mesothelioma.
Austin Authors: Chia, Puey Ling ;Parakh, Sagun ;Tsao, Ming-Sound;Pham, Nhu-An;Gan, Hui K ;Cao, Diana;Burvenich, Ingrid J G;Rigopoulos, Angela;Reilly, Edward B;John, Thomas ;Scott, Andrew M 
Affiliation: Olivia Newton-John Cancer Research Institute
Princess Margaret Cancer Centre, University Health Network, Toronto, ON M5G 2C1, Canada
Medical Oncology
School of Cancer Medicine, La Trobe University, Plenty Rd &, Kingsbury Dr, Bundoora, Victoria 3086, Australia
Faculty of Medicine, University of Melbourne, Melbourne, Victoria 3010, Australia
Molecular Imaging and Therapy
AbbVie Inc., North Chicago, IL 60064, USA
Issue Date: 2-Oct-2020
Date: 2020-10-02
Publication information: Pharmaceuticals 2020; 13(10); 289
Abstract: Epidermal 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.
DOI: 10.3390/ph13100289
ORCID: 0000-0002-9160-5405
Journal: Pharmaceuticals
PubMed URL: 33023139
ISSN: 1424-8247
Type: Journal Article
Subjects: 806-ADC
malignant mesothelioma
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