Development of monoclonal anti-PDGF-CC antibodies as tools for investigating human tissue expression and for blocking PDGF-CC induced PDGFRα signalling in vivo
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...
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| creator | Li, Hong Zeitelhofer, Manuel Nilsson, Ingrid Liu, Xicong Allan, Laura Gloria, Benjamin Perani, Angelo Murone, Carmel Catimel, Bruno Neville, A Munro Scott, Fiona E Scott, Andrew M Eriksson, Ulf |
| description | 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_str_mv | 10.1371/journal.pone.0201089 |
| format | Article |
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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.</description><identifier>ISSN: 1932-6203</identifier><identifier>EISSN: 1932-6203</identifier><identifier>DOI: 10.1371/journal.pone.0201089</identifier><identifier>PMID: 30052660</identifier><language>eng</language><publisher>United States: Public Library of Science</publisher><subject>A549 Cells ; Affinity ; Animals ; Antibodies, Monoclonal - immunology ; Biochemistry ; Biology and Life Sciences ; Biophysics ; Blood platelets ; Blood-brain barrier ; Blood-Retinal Barrier - drug effects ; Blood-Retinal Barrier - metabolism ; Blood-Retinal Barrier - pathology ; Brain research ; Breast cancer ; Cancer ; Capillary Permeability ; Complementarity ; Diabetic retinopathy ; Epitopes ; Fibroblasts ; Fibrosis ; Gene Expression - drug effects ; Growth factors ; Humans ; Immunoglobulins ; Immunohistochemistry ; Intracellular signalling ; Lymphokines - antagonists & inhibitors ; Lymphokines - immunology ; Medical research ; Medicine ; Medicine and Health Sciences ; Mice, Inbred C57BL ; Mice, Transgenic ; Monoclonal antibodies ; Neoplasms - metabolism ; Neoplasms - pathology ; Newton-John, Olivia ; Phosphorylation ; Platelet-derived growth factor ; Platelet-Derived Growth Factor - antagonists & inhibitors ; Platelet-Derived Growth Factor - immunology ; Receptor, Platelet-Derived Growth Factor alpha - metabolism ; Recombinant Proteins - immunology ; Research and Analysis Methods ; Retina ; Rodents ; Signal Transduction - drug effects ; Tumors</subject><ispartof>PloS one, 2018, Vol.13 (7), p.e0201089</ispartof><rights>2018 Li et al. This is an open access article distributed under the terms of the Creative Commons Attribution License: http://creativecommons.org/licenses/by/4.0/ (the “License”), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. Notwithstanding the ProQuest Terms and Conditions, you may use this content in accordance with the terms of the License.</rights><rights>2018 Li et al 2018 Li et al</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c564t-b184e51d9e3d980be4f883b257f85edd8c525eba1590d24d27eca0bfe99534a23</citedby><cites>FETCH-LOGICAL-c564t-b184e51d9e3d980be4f883b257f85edd8c525eba1590d24d27eca0bfe99534a23</cites><orcidid>0000-0002-4439-3980</orcidid></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC6063412/pdf/$$EPDF$$P50$$Gpubmedcentral$$Hfree_for_read</linktopdf><linktohtml>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC6063412/$$EHTML$$P50$$Gpubmedcentral$$Hfree_for_read</linktohtml><link.rule.ids>230,314,550,723,776,780,860,881,2096,2915,4010,23845,27900,27901,27902,53766,53768,79342,79343</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/30052660$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink><backlink>$$Uhttp://kipublications.ki.se/Default.aspx?queryparsed=id:138851935$$DView record from Swedish Publication Index$$Hfree_for_read</backlink></links><search><creatorcontrib>Li, Hong</creatorcontrib><creatorcontrib>Zeitelhofer, Manuel</creatorcontrib><creatorcontrib>Nilsson, Ingrid</creatorcontrib><creatorcontrib>Liu, Xicong</creatorcontrib><creatorcontrib>Allan, Laura</creatorcontrib><creatorcontrib>Gloria, Benjamin</creatorcontrib><creatorcontrib>Perani, Angelo</creatorcontrib><creatorcontrib>Murone, Carmel</creatorcontrib><creatorcontrib>Catimel, Bruno</creatorcontrib><creatorcontrib>Neville, A Munro</creatorcontrib><creatorcontrib>Scott, Fiona E</creatorcontrib><creatorcontrib>Scott, Andrew M</creatorcontrib><creatorcontrib>Eriksson, Ulf</creatorcontrib><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</title><title>PloS one</title><addtitle>PLoS One</addtitle><description>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.</description><subject>A549 Cells</subject><subject>Affinity</subject><subject>Animals</subject><subject>Antibodies, Monoclonal - immunology</subject><subject>Biochemistry</subject><subject>Biology and Life Sciences</subject><subject>Biophysics</subject><subject>Blood platelets</subject><subject>Blood-brain barrier</subject><subject>Blood-Retinal Barrier - drug effects</subject><subject>Blood-Retinal Barrier - metabolism</subject><subject>Blood-Retinal Barrier - pathology</subject><subject>Brain research</subject><subject>Breast cancer</subject><subject>Cancer</subject><subject>Capillary Permeability</subject><subject>Complementarity</subject><subject>Diabetic retinopathy</subject><subject>Epitopes</subject><subject>Fibroblasts</subject><subject>Fibrosis</subject><subject>Gene Expression - drug effects</subject><subject>Growth factors</subject><subject>Humans</subject><subject>Immunoglobulins</subject><subject>Immunohistochemistry</subject><subject>Intracellular signalling</subject><subject>Lymphokines - antagonists & inhibitors</subject><subject>Lymphokines - immunology</subject><subject>Medical research</subject><subject>Medicine</subject><subject>Medicine and Health Sciences</subject><subject>Mice, Inbred C57BL</subject><subject>Mice, Transgenic</subject><subject>Monoclonal antibodies</subject><subject>Neoplasms - metabolism</subject><subject>Neoplasms - pathology</subject><subject>Newton-John, Olivia</subject><subject>Phosphorylation</subject><subject>Platelet-derived growth factor</subject><subject>Platelet-Derived Growth Factor - antagonists & inhibitors</subject><subject>Platelet-Derived Growth Factor - immunology</subject><subject>Receptor, Platelet-Derived Growth Factor alpha - metabolism</subject><subject>Recombinant Proteins - immunology</subject><subject>Research and Analysis Methods</subject><subject>Retina</subject><subject>Rodents</subject><subject>Signal Transduction - drug effects</subject><subject>Tumors</subject><issn>1932-6203</issn><issn>1932-6203</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2018</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><sourceid>BENPR</sourceid><sourceid>D8T</sourceid><sourceid>DOA</sourceid><recordid>eNp1UtuO0zAQjRCIXQp_gMASzym-xUlekFCXXVZaCYTg2bLjSdfd1A52EuBv-AV-hG_CbdPV9oEnj8fnnJnxnCx7SfCSsJK83fgxONUte-9giSkmuKofZeekZjQXFLPHD-Kz7FmMG4wLVgnxNDtjKaRC4PPs9wVM0Pl-C25AvkVb73zT-SSMlBts_vni6jJfrfYX7Y2FiFREg_ddRK0PyLoJ4mDXarBujW7HrXJosDGOgOBnHyBG611imz1ad7652wGPstaZsQGzv3_5-wdFu06lux3EOjTZyT_PnrSqi_BiPhfZt8sPX1cf85tPV9er9zd5Uwg-5JpUHApiamCmrrAG3lYV07Qo26oAY6qmoAVoRYoaG8oNLaFRWLdQ1wXjirJF9vqg23c-yvlzo6S4LHkhMCMJcX1AGK82sg92q8Iv6ZWV-4QPa6nCYJsOJGtFZVpctmAwJxhXWpR1bQSuGeNU6aSVH7TiD-hHfaI2p-5SBJKnhaVBFtm7ubtRb8E0aVtBdSe00xdnb-XaT1JgwTjZjfdmFgj--5hW9p8R-QHVBB9jgPa-AsFy57ojS-5cJ2fXJdqrh93dk442Y_8AgNHZSg</recordid><startdate>2018</startdate><enddate>2018</enddate><creator>Li, Hong</creator><creator>Zeitelhofer, Manuel</creator><creator>Nilsson, Ingrid</creator><creator>Liu, Xicong</creator><creator>Allan, Laura</creator><creator>Gloria, Benjamin</creator><creator>Perani, Angelo</creator><creator>Murone, Carmel</creator><creator>Catimel, Bruno</creator><creator>Neville, A Munro</creator><creator>Scott, Fiona E</creator><creator>Scott, Andrew M</creator><creator>Eriksson, Ulf</creator><general>Public Library of Science</general><general>Public Library of Science (PLoS)</general><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>3V.</scope><scope>7QG</scope><scope>7QL</scope><scope>7QO</scope><scope>7RV</scope><scope>7SN</scope><scope>7SS</scope><scope>7T5</scope><scope>7TG</scope><scope>7TM</scope><scope>7U9</scope><scope>7X2</scope><scope>7X7</scope><scope>7XB</scope><scope>88E</scope><scope>8AO</scope><scope>8C1</scope><scope>8FD</scope><scope>8FE</scope><scope>8FG</scope><scope>8FH</scope><scope>8FI</scope><scope>8FJ</scope><scope>8FK</scope><scope>ABJCF</scope><scope>ABUWG</scope><scope>AEUYN</scope><scope>AFKRA</scope><scope>ARAPS</scope><scope>ATCPS</scope><scope>AZQEC</scope><scope>BBNVY</scope><scope>BENPR</scope><scope>BGLVJ</scope><scope>BHPHI</scope><scope>C1K</scope><scope>CCPQU</scope><scope>D1I</scope><scope>DWQXO</scope><scope>FR3</scope><scope>FYUFA</scope><scope>GHDGH</scope><scope>GNUQQ</scope><scope>H94</scope><scope>HCIFZ</scope><scope>K9.</scope><scope>KB.</scope><scope>KB0</scope><scope>KL.</scope><scope>L6V</scope><scope>LK8</scope><scope>M0K</scope><scope>M0S</scope><scope>M1P</scope><scope>M7N</scope><scope>M7P</scope><scope>M7S</scope><scope>NAPCQ</scope><scope>P5Z</scope><scope>P62</scope><scope>P64</scope><scope>PATMY</scope><scope>PDBOC</scope><scope>PIMPY</scope><scope>PQEST</scope><scope>PQQKQ</scope><scope>PQUKI</scope><scope>PRINS</scope><scope>PTHSS</scope><scope>PYCSY</scope><scope>RC3</scope><scope>5PM</scope><scope>ADTPV</scope><scope>AOWAS</scope><scope>D8T</scope><scope>ZZAVC</scope><scope>DOA</scope><orcidid>https://orcid.org/0000-0002-4439-3980</orcidid></search><sort><creationdate>2018</creationdate><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</title><author>Li, Hong ; Zeitelhofer, Manuel ; Nilsson, Ingrid ; Liu, Xicong ; Allan, Laura ; Gloria, Benjamin ; Perani, Angelo ; Murone, Carmel ; Catimel, Bruno ; Neville, A Munro ; Scott, Fiona E ; Scott, Andrew M ; Eriksson, Ulf</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c564t-b184e51d9e3d980be4f883b257f85edd8c525eba1590d24d27eca0bfe99534a23</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2018</creationdate><topic>A549 Cells</topic><topic>Affinity</topic><topic>Animals</topic><topic>Antibodies, Monoclonal - immunology</topic><topic>Biochemistry</topic><topic>Biology and Life Sciences</topic><topic>Biophysics</topic><topic>Blood platelets</topic><topic>Blood-brain barrier</topic><topic>Blood-Retinal Barrier - drug effects</topic><topic>Blood-Retinal Barrier - metabolism</topic><topic>Blood-Retinal Barrier - pathology</topic><topic>Brain research</topic><topic>Breast cancer</topic><topic>Cancer</topic><topic>Capillary Permeability</topic><topic>Complementarity</topic><topic>Diabetic retinopathy</topic><topic>Epitopes</topic><topic>Fibroblasts</topic><topic>Fibrosis</topic><topic>Gene Expression - drug effects</topic><topic>Growth factors</topic><topic>Humans</topic><topic>Immunoglobulins</topic><topic>Immunohistochemistry</topic><topic>Intracellular signalling</topic><topic>Lymphokines - antagonists & inhibitors</topic><topic>Lymphokines - immunology</topic><topic>Medical research</topic><topic>Medicine</topic><topic>Medicine and Health Sciences</topic><topic>Mice, Inbred C57BL</topic><topic>Mice, Transgenic</topic><topic>Monoclonal antibodies</topic><topic>Neoplasms - 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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.</abstract><cop>United States</cop><pub>Public Library of Science</pub><pmid>30052660</pmid><doi>10.1371/journal.pone.0201089</doi><orcidid>https://orcid.org/0000-0002-4439-3980</orcidid><oa>free_for_read</oa></addata></record> |
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| source | MEDLINE; DOAJ Directory of Open Access Journals; Elektronische Zeitschriftenbibliothek - Frei zugängliche E-Journals; PubMed Central; SWEPUB Freely available online; Free Full-Text Journals in Chemistry; Public Library of Science (PLoS) |
| subjects | A549 Cells Affinity Animals Antibodies, Monoclonal - immunology Biochemistry Biology and Life Sciences Biophysics Blood platelets Blood-brain barrier Blood-Retinal Barrier - drug effects Blood-Retinal Barrier - metabolism Blood-Retinal Barrier - pathology Brain research Breast cancer Cancer Capillary Permeability Complementarity Diabetic retinopathy Epitopes Fibroblasts Fibrosis Gene Expression - drug effects Growth factors Humans Immunoglobulins Immunohistochemistry Intracellular signalling Lymphokines - antagonists & inhibitors Lymphokines - immunology Medical research Medicine Medicine and Health Sciences Mice, Inbred C57BL Mice, Transgenic Monoclonal antibodies Neoplasms - metabolism Neoplasms - pathology Newton-John, Olivia Phosphorylation Platelet-derived growth factor Platelet-Derived Growth Factor - antagonists & inhibitors Platelet-Derived Growth Factor - immunology Receptor, Platelet-Derived Growth Factor alpha - metabolism Recombinant Proteins - immunology Research and Analysis Methods Retina Rodents Signal Transduction - drug effects Tumors |
| 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 |
| url | https://sfx.bib-bvb.de/sfx_tum?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&ctx_tim=2025-02-08T11%3A29%3A37IST&url_ver=Z39.88-2004&url_ctx_fmt=infofi/fmt:kev:mtx:ctx&rfr_id=info:sid/primo.exlibrisgroup.com:primo3-Article-proquest_plos_&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.atitle=Development%20of%20monoclonal%20anti-PDGF-CC%20antibodies%20as%20tools%20for%20investigating%20human%20tissue%20expression%20and%20for%20blocking%20PDGF-CC%20induced%20PDGFR%CE%B1%20signalling%20in%20vivo&rft.jtitle=PloS%20one&rft.au=Li,%20Hong&rft.date=2018&rft.volume=13&rft.issue=7&rft.spage=e0201089&rft.pages=e0201089-&rft.issn=1932-6203&rft.eissn=1932-6203&rft_id=info:doi/10.1371/journal.pone.0201089&rft_dat=%3Cproquest_plos_%3E2077456031%3C/proquest_plos_%3E%3Curl%3E%3C/url%3E&disable_directlink=true&sfx.directlink=off&sfx.report_link=0&rft_id=info:oai/&rft_pqid=2077456031&rft_id=info:pmid/30052660&rft_doaj_id=oai_doaj_org_article_3f68df07fed041008b6799d6093342ab&rfr_iscdi=true |