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Development of monoclonal anti-PDGF-CC antibodies as tools for investigating human tissue expression and for blocking PDGF-CC induced PDGFRα signalling in vivo

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posted on 2023-05-10, 06:34 authored by Hong Li, Manuel Zeitelhofer, Ingrid Nilsson, Xicong Liu, Laura Allan, Benjamin Gloria, Angelo Perani, Carmel Murone, Bruno Catimel, A Munro Neville, Fiona ScottFiona Scott, Andrew ScottAndrew 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.

Funding

This study was supported by the Swedish Heart and Lung Foundation (20110451 and 20120077, U.E.), the Swedish Research Council (2011-03861, U.E.), the Swedish Cancer Foundation (CAN 2011/792 and CAN 2014/630, U.E.), and the Karolinska Institutet. This work was supported in part by the Australian National Health and Medical Research Council (NHMRC).

History

Publication Date

2018-07-27

Journal

PLoS One

Volume

13

Issue

7

Article Number

e0201089

Pagination

20p. (p. 1-20)

Publisher

PLOS

ISSN

1932-6203

Rights Statement

© 2018 Li et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

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