Conformation-Specific Inhibitory Anti-MMP-7 Monoclonal Antibody Sensitizes Pancreatic Ductal Adenocarcinoma Cells to Chemotherapeutic Cell Kill.

drug synergy fas ligand gemcitabine matrilysin matrix metalloproteinase-7 monoclonal antibody oxaliplatin pancreatic ductal adenocarcinoma

Journal

Cancers
ISSN: 2072-6694
Titre abrégé: Cancers (Basel)
Pays: Switzerland
ID NLM: 101526829

Informations de publication

Date de publication:
02 Apr 2021
Historique:
received: 23 02 2021
revised: 23 03 2021
accepted: 30 03 2021
entrez: 30 4 2021
pubmed: 1 5 2021
medline: 1 5 2021
Statut: epublish

Résumé

Matrix metalloproteases (MMPs) undergo post-translational modifications including pro-domain shedding. The activated forms of these enzymes are effective drug targets, but generating potent biological inhibitors against them remains challenging. We report the generation of anti-MMP-7 inhibitory monoclonal antibody (GSM-192), using an alternating immunization strategy with an active site mimicry antigen and the activated enzyme. Our protocol yielded highly selective anti-MMP-7 monoclonal antibody, which specifically inhibits MMP-7's enzyme activity with high affinity (IC

Identifiants

pubmed: 33918254
pii: cancers13071679
doi: 10.3390/cancers13071679
pmc: PMC8038143
pii:
doi:

Types de publication

Journal Article

Langues

eng

Subventions

Organisme : European Union Framework Programme 7 [FP7/2007-2013] "SaveMe"
ID : 263307
Organisme : Israeli Science Foundation
ID : 1800/19
Organisme : NCI NIH HHS
ID : P30 CA008748
Pays : United States
Organisme : The Thompson Family Foundation, Inc. grant
ID : Targeting Pancreas Cancer
Organisme : European Union's Horizon 2020 research and innovation programme
ID : 801126
Organisme : European Research Council (ERC) under the European Union's Horizon 2020 research and innovation programme
ID : 695437
Organisme : Big C
ID : 14-09R
Organisme : The USA-Israel Binational Science Foundation
ID : 712506-01

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Auteurs

Vishnu Mohan (V)

Department of Biological Regulation, Weizmann Institute of Science, Rehovot IL76100, Israel.

Jean P Gaffney (JP)

Department of Biological Regulation, Weizmann Institute of Science, Rehovot IL76100, Israel.

Inna Solomonov (I)

Department of Biological Regulation, Weizmann Institute of Science, Rehovot IL76100, Israel.

Maxim Levin (M)

Department of Biological Regulation, Weizmann Institute of Science, Rehovot IL76100, Israel.

Mordehay Klepfish (M)

Department of Biological Regulation, Weizmann Institute of Science, Rehovot IL76100, Israel.

Sophia Akbareian (S)

School of Biological Sciences, University of East Anglia, Norwich NR4 7TJ, UK.

Barbara Grünwald (B)

Institut für Molekulare Immunologie und Experimentelle Onkologie, Klinikum Rechts der Isar der Technischen Universität München, 81675 Munich, Germany.

Orly Dym (O)

Structural Proteomics Unit, Faculty of Biochemistry, Weizmann Institute of Science, Rehovot IL76100, Israel.

Miriam Eisenstein (M)

Department of Molecular Genetics, Faculty of Biochemistry, Weizmann Institute of Science, Rehovot IL76100, Israel.

Kenneth H Yu (KH)

Department of Medicine, Memorial Sloan Kettering Cancer, New York, NY 10065, USA.

David P Kelsen (DP)

Department of Medicine, Memorial Sloan Kettering Cancer, New York, NY 10065, USA.

Achim Krüger (A)

Institut für Molekulare Immunologie und Experimentelle Onkologie, Klinikum Rechts der Isar der Technischen Universität München, 81675 Munich, Germany.

Dylan R Edwards (DR)

School of Biological Sciences, University of East Anglia, Norwich NR4 7TJ, UK.

Irit Sagi (I)

Department of Biological Regulation, Weizmann Institute of Science, Rehovot IL76100, Israel.

Classifications MeSH