Publication Date:
2018-07-28
Description:
by Hong Li, Manuel Zeitelhofer, Ingrid Nilsson, Xicong Liu, Laura Allan, Benjamin Gloria, Angelo Perani, Carmel Murone, Bruno Catimel, A. Munro Neville, Fiona E. Scott, Andrew M. Scott, Ulf Eriksson 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 .
Electronic ISSN:
1932-6203
Topics:
Medicine
,
Natural Sciences in General
