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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.
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.
Afiliación
  • Li H; Department of Medical Biochemistry and Biophysics, Karolinska Institutet, Stockholm, Sweden.
  • Zeitelhofer M; Department of Medical Biochemistry and Biophysics, Karolinska Institutet, Stockholm, Sweden.
  • Nilsson I; Department of Medical Biochemistry and Biophysics, Karolinska Institutet, Stockholm, Sweden.
  • Liu X; Department of Medical Biochemistry and Biophysics, Karolinska Institutet, Stockholm, Sweden.
  • Allan L; Ludwig institute for Cancer Research, Melbourne Austin Branch, Melbourne, Australia.
  • Gloria B; Olivia Newton-John Cancer Research Institute, and School of Cancer Medicine, La Trobe University, Melbourne, Australia.
  • Perani A; Ludwig institute for Cancer Research, Melbourne Austin Branch, Melbourne, Australia.
  • Murone C; Olivia Newton-John Cancer Research Institute, and School of Cancer Medicine, La Trobe University, Melbourne, Australia.
  • Catimel B; Ludwig institute for Cancer Research, Melbourne Austin Branch, Melbourne, Australia.
  • Neville AM; Ludwig institute for Cancer Research, Melbourne Austin Branch, Melbourne, Australia.
  • Scott FE; Olivia Newton-John Cancer Research Institute, and School of Cancer Medicine, La Trobe University, Melbourne, Australia.
  • Scott AM; Ludwig institute for Cancer Research, Melbourne Austin Branch, Melbourne, Australia.
  • Eriksson U; Ludwig Institute for Cancer Research, New York, New York, United States of America.
PLoS One ; 13(7): e0201089, 2018.
Article en En | MEDLINE | ID: mdl-30052660
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.
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Factor de Crecimiento Derivado de Plaquetas / Linfocinas / Receptor alfa de Factor de Crecimiento Derivado de Plaquetas / Anticuerpos Monoclonales Límite: Animals / Humans Idioma: En Revista: PLoS One Asunto de la revista: CIENCIA / MEDICINA Año: 2018 Tipo del documento: Article País de afiliación: Suecia Pais de publicación: Estados Unidos
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Factor de Crecimiento Derivado de Plaquetas / Linfocinas / Receptor alfa de Factor de Crecimiento Derivado de Plaquetas / Anticuerpos Monoclonales Límite: Animals / Humans Idioma: En Revista: PLoS One Asunto de la revista: CIENCIA / MEDICINA Año: 2018 Tipo del documento: Article País de afiliación: Suecia Pais de publicación: Estados Unidos