title: Rendomab B4, a monoclonal antibody that discriminates the human endothelin B receptor of melanoma cells and inhibits their migration.
abstract: Metastatic melanoma is an aggressive cancer with a poor prognostic, and the design of new targeted drugs to treat melanoma is a therapeutic challenge. A promising approach is to produce monoclonal antibodies (mAbs) against the endothelin B receptor (ETB), which is known to be overexpressed in melanoma and to contribute to proliferation, migration and vasculogenic mimicry associated with invasiveness of this cancer. We previously described rendomab-B1, a mAb produced by DNA immunization. It is endowed with remarkable characteristics in term of affinity, specificity and antagonist properties against human ETB expressed by the endothelial cells, but, surprisingly, had poor affinity for ETB expressed by melanoma cells. This characteristic strongly suggested the existence of a tumor-specific ETB form. In the study reported here, we identified a new mAb, rendomab-B4, which, in contrast to rendomab-B1, binds ETB expressed on UACC-257, WM-266-4 and SLM8 melanoma cells. Moreover, after binding to UACC-257 cells, rendomab-B4 is internalized and colocalizes with the endosomal protein EEA-1. Interestingly, rendomab-B4, despite its inability to compete with endothelin binding, is able to inhibit phospholipase C pathway and migration induced by endothelin. By contrast, rendomab-B4 fails to decrease ERK1/2 phosphorylation induced by endothelin, suggesting a biased effect on ETB. These particular properties make rendomab-B4 an interesting tool to analyze ETB-structure/function and a promising starting point for the development of new immunological tools in the field of melanoma therapeutics.
authors.affiliation: a CEA, iBiTec-S, SPI, Laboratoire d'Ingénierie des Anticorps pour la Santé , Gif-sur-Yvette , France.|b Université Paris Sud-11 , CNRS, UMR 8619, IBBMC , Orsay , France.
authors.forename: Aurélie
authors.initials: A
authors.lastname: Borrull
authors.affiliation: a CEA, iBiTec-S, SPI, Laboratoire d'Ingénierie des Anticorps pour la Santé , Gif-sur-Yvette , France.
authors.forename: Bertrand
authors.initials: B
authors.lastname: Allard
authors.affiliation: a CEA, iBiTec-S, SPI, Laboratoire d'Ingénierie des Anticorps pour la Santé , Gif-sur-Yvette , France.|c Université Paris Diderot, Sorbonne Paris Cité , Gif-sur-Yvette , France.
authors.forename: Anne
authors.initials: A
authors.lastname: Wijkhuisen
authors.affiliation: a CEA, iBiTec-S, SPI, Laboratoire d'Ingénierie des Anticorps pour la Santé , Gif-sur-Yvette , France.
authors.forename: Amaury
authors.initials: A
authors.lastname: Herbet
authors.affiliation: d CEA, iBiTec-S, SPI, Laboratoire d'Etude et de Recherche en Immunoanalyse , Gif-sur-Yvette , France.
authors.forename: Patricia
authors.initials: P
authors.lastname: Lamourette
authors.affiliation: b Université Paris Sud-11 , CNRS, UMR 8619, IBBMC , Orsay , France.
authors.forename: Wided
authors.initials: W
authors.lastname: Birouk
authors.affiliation: b Université Paris Sud-11 , CNRS, UMR 8619, IBBMC , Orsay , France.
authors.forename: Denis
authors.initials: D
authors.lastname: Leiber
authors.affiliation: b Université Paris Sud-11 , CNRS, UMR 8619, IBBMC , Orsay , France.
authors.forename: Zahra
authors.initials: Z
authors.lastname: Tanfin
authors.affiliation: a CEA, iBiTec-S, SPI, Laboratoire d'Ingénierie des Anticorps pour la Santé , Gif-sur-Yvette , France.
authors.forename: Frédéric
authors.initials: F
authors.lastname: Ducancel
authors.affiliation: a CEA, iBiTec-S, SPI, Laboratoire d'Ingénierie des Anticorps pour la Santé , Gif-sur-Yvette , France.
authors.forename: Didier
authors.initials: D
authors.lastname: Boquet
authors.affiliation: a CEA, iBiTec-S, SPI, Laboratoire d'Ingénierie des Anticorps pour la Santé , Gif-sur-Yvette , France.|c Université Paris Diderot, Sorbonne Paris Cité , Gif-sur-Yvette , France.
authors.forename: Jean-Yves
authors.initials: JY
authors.lastname: Couraud
authors.affiliation: b Université Paris Sud-11 , CNRS, UMR 8619, IBBMC , Orsay , France.
authors.forename: Philippe
authors.initials: P
authors.lastname: Robin
mesh_terms: D000911:Antibodies, Monoclonal / Q000494:pharmacology*; D000970:Antineoplastic Agents / Q000494:pharmacology*; D045744:Cell Line, Tumor; D065131:Endothelin B Receptor Antagonists / Q000494:pharmacology*; D006801:Humans; D008545:Melanoma; D044023:Receptor, Endothelin B / Q000276:immunology*
chemical_list: D000911:Antibodies, Monoclonal; D000970:Antineoplastic Agents; D065131:Endothelin B Receptor Antagonists; D044023:Receptor, Endothelin B; C000624531:rendomab-B4
keywords: Cancer; MAPK; endothelin; endothelin B receptor; melanoma; migration; monoclonal antibody; phospholipase C