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Title: Development of monoclonal anti-PDGF-CC antibodies as tools for investigating human tissue expression and for blocking PDGF-CC induced PDGFRα signalling in vivo.
Authors: Li, Hong;Zeitelhofer, Manuel;Nilsson, Ingrid;Liu, Xicong;Allan, Laura C;Gloria, Benjamin;Perani, Angelo;Murone, Carmel;Catimel, Bruno;Neville, A Munro;Scott, Fiona E;Scott, Andrew M;Eriksson, Ulf
Affiliation: Department of Medical Biochemistry and Biophysics, Karolinska Institutet, Stockholm, Sweden
Ludwig Institute for Cancer Research, Austin Health, Heidelberg, Victoria, Australia
Ludwig Institute for Cancer Research, New York, New York, United States of America
Olivia Newton-John Cancer Research Institute, Heidelberg, Victoria, Australia
School of Cancer Medicine, La Trobe University, Melbourne, Australia
Issue Date: 27-Jul-2018
EDate: 2018-07-27
Citation: PloS one 2018; 13(7): e0201089
Abstract: PDGF-CC is a member of the platelet-derived growth factor (PDGF) family that stimulates PDGFRα phosphorylation and thereby activates intracellular signalling events essential for development but also in cancer, fibrosis and neuropathologies involving blood-brain barrier (BBB) disruption. In order to elucidate the biological and pathological role(s) of PDGF-CC signalling, we have generated high affinity neutralizing monoclonal antibodies (mAbs) recognizing human PDGF-CC. We determined the complementarity determining regions (CDRs) of the selected clones, and mapped the binding epitope for clone 6B3. Using the monoclonal 6B3, we determined the expression pattern for PDGF-CC in different human primary tumours and control tissues, and explored its ability to neutralize PDGF-CC-induced phosphorylation of PDGFRα. In addition, we showed that PDGF-CC induced disruption of the blood-retinal barrier (BRB) was significantly reduced upon intraperitoneal administration of a chimeric anti-PDGF-CC antibody. In summary, we report on high affinity monoclonal antibodies against PDGF-CC that have therapeutic efficacy in vivo.
DOI: 10.1371/journal.pone.0201089
PubMed URL: 30052660
Type: Journal Article
Appears in Collections:Journal articles

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