Please use this identifier to cite or link to this item: https://ahro.austin.org.au/austinjspui/handle/1/25057
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
metadata.dc.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.
URI: https://ahro.austin.org.au/austinjspui/handle/1/25057
DOI: 10.3390/ph13100289
ORCID: 0000-0002-9160-5405
0000-0001-8384-2403
PubMed URL: 33023139
ISSN: 1424-8247
Type: Journal Article
Subjects: 806-ADC
89Zr-ch806
EGFR
malignant mesothelioma
Appears in Collections:Journal articles

Show full item record

Page view(s)

24
checked on May 8, 2021

Google ScholarTM

Check


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