Generation and characterization of rendomab-B1, a monoclonal antibody displaying potent and specific antagonism of the human endothelin B receptor
| Autor: | Aurélie Borrull, Patricia Lamourette, Jean-Yves Couraud, Frédérique Deshayes, Frédéric Ducancel, Bertrand Allard, Didier Boquet, Fabienne Priam, Anne Wijkhuisen |
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| Přispěvatelé: | Laboratoire d'Ingénierie des Anticorps pour la Santé (LIAS), Commissariat à l'énergie atomique et aux énergies alternatives (CEA), Anticorps recombinants, anticorps pharmacologiques, immunothérapie (EA_3515), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Université Paris Diderot - Paris 7 (UPD7), Institut Jacques Monod (IJM (UMR_7592)), Université Paris Diderot - Paris 7 (UPD7)-Centre National de la Recherche Scientifique (CNRS), Commissariat a l'Energie Atomique (CEA, France) Ministere de l'Enseignement Superieur et de la Recherche EA 3515 ED 425, Université Paris Diderot - Paris 7 (UPD7)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA) |
| Rok vydání: | 2013 |
| Předmět: |
Endothelin receptor type A
Cell Survival Angiogenesis Endothelin B Receptor Antagonists Immunology [SDV.CAN]Life Sciences [q-bio]/Cancer CHO Cells Biology GPCRs Cell Line Receptors G-Protein-Coupled Mice Report Cell Line Tumor Cricetinae Human Umbilical Vein Endothelial Cells melanoma Animals Humans Immunology and Allergy Receptor G protein-coupled receptor genetic immunization HEK 293 cells Antibodies Monoclonal antagonist DNA Receptor Endothelin B Molecular biology 3. Good health Cell biology Mice Inbred C57BL HEK293 Cells endothelin B receptor monoclonal antibody Cancer cell Female Immunization [SDV.MHEP]Life Sciences [q-bio]/Human health and pathology Conformational epitope |
| Zdroj: | mAbs mAbs, 2013, 5 (1), pp.56-69. ⟨10.4161/mabs.22696⟩ mAbs, Taylor & Francis, 2013, 5 (1), pp.56-69. ⟨10.4161/mabs.22696⟩ |
| ISSN: | 1942-0870 1942-0862 |
| DOI: | 10.4161/mabs.22696 |
| Popis: | International audience; Endothelin B receptor (ETBR) is a G protein-coupled receptor able to bind equally to the three identified human endothelin peptides. It is expressed primarily on vascular endothelial cells and involved in various physiological processes including vascular tone homeostasis, enteric nervous system development, melanogenesis and angiogenesis. Furthermore, overactivation or overexpression of ETBR have been associated with the development of various diseases such as cardiovascular disorders and cancers. Therefore, ETBR appears to be relevant target for the therapy or diagnosis of highly prevalent human diseases. In this study, we report the in vitro characterization of rendomab-B1, a monoclonal antibody (mAb) obtained by genetic immunization, which selectively recognizes the native form of human ETBR (hETBR). Rendomab-B1 is the first-reported mAb that behaves as a potent antagonist of hETBR. It recognizes an original extracellular conformational epitope on the receptor, distinct from the endothelin-1 (ET-1) binding site. Rendomab-B1 not only blocks ET-1-induced calcium signaling pathway and triggers rapid receptor internalization on recombinant hETBR-expressing cells, but also exerts pharmacological activities on human vascular endothelial cells, reducing both cell viability and ET-1-induced hETBR synthesis. In addition, binding experiments using rendomab-B1 on different melanoma cell lines reveal the structural and functional heterogeneity of hETBR expressed at the surface of these cancer cells, strongly suggesting the existence of tumor-specific receptors. Collectively, our results underscore the value of rendomab-B1 for research, therapeutic and diagnostic applications dealing with hETBR. |
| Databáze: | OpenAIRE |
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