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Title: Preferential Antibody and Drug Conjugate Targeting of the ADAM10 Metalloprotease in Tumours.
Austin Authors: Yan, Hengkang;Vail, Mary E;Hii, Linda;Guo, Nancy;McMurrick, Paul J;Oliva, Karen;Wilkins, Simon;Saha, Nayanendu;Nikolov, Dimitar B;Lee, Fook-Thean;Scott, Andrew M ;Janes, Peter W 
Affiliation: Department of Epidemiology and Preventive Medicine, Monash University, Melbourne, VIC 3004, Australia..
Olivia Newton-John Cancer Research Institute
School of Cancer Medicine, La Trobe University, Heidelberg, VIC 3084, Australia..
Monash Biomedicine Discovery Institute, Department of Biochemistry and Molecular Biology, Monash University, Clayton, VIC 3800, Australia..
Cabrini Monash University Department of Surgery, Cabrini Hospital, Malvern, VIC 3144, Australia..
Structural Biology Program, Memorial Sloan-Kettering Cancer Centre, New York, NY 10065, USA..
Issue Date: 28-Jun-2022
Date: 2022
Publication information: Cancers 2022; 14(13): 3171
Abstract: ADAM10 is a transmembrane metalloprotease that sheds a variety of cell surface proteins, including receptors and ligands that regulate a range of developmental processes which re-emerge during tumour development. While ADAM10 is ubiquitously expressed, its activity is normally tightly regulated, but becomes deregulated in tumours. We previously reported the generation of a monoclonal antibody, 8C7, which preferentially recognises an active form of ADAM10 in human and mouse tumours. We now report our investigation of the mechanism of this specificity, and the preferential targeting of 8C7 to human tumour cell xenografts in mice. We also report the development of novel 8C7 antibody-drug conjugates that preferentially kill cells displaying the 8C7 epitope, and that can inhibit tumour growth in mice. This study provides the first demonstration that antibody-drug conjugates targeting an active conformer of ADAM10, a widely expressed transmembrane metalloprotease, enable tumour-selective targeting and inhibition.
DOI: 10.3390/cancers14133171
ORCID: 0000-0002-2856-2959
Journal: Cancers
PubMed URL: 35804938
PubMed URL:
ISSN: 2072-6694
Type: Journal Article
Subjects: ADAM metalloprotease
antibody–drug conjugate
brain cancer
colon cancer
therapeutic antibody
Appears in Collections:Journal articles

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