Production and characterization of polyclonal and monoclonal antibodies targeting endothelin receptors for cancer immunotherapy
type: Dataset
description: For a decade, monoclonal antibodies have become increasingly important for the biotherapeutic management of cancer. However, none of the monoclonal antibodies currently on the market or in late stage clinical trial do target a G-protein coupled receptor in spite of the emerging role of these receptors in tumor progression. Among the therapeutically relevant GPCRs for oncology, the endothelin receptors (ETAR and ETBR) are particularly attractive considering their overexpression in a wide range of tumors and their involvement in various stages of tumorigenesis. In this context, my PhD project consisted in producing and characterizing monoclonal antibodies directed against endothelin receptors with a view to use them as anti-tumor agents. Using an original DNA immunization strategy, we produced a panel of 27 monoclonal antibodies which selectively recognized ETBR expressed at the surface of transfected cells. One of these antibodies, named rendomab-B1, was extensively characterized and proved to be a potent allosteric antagonist of ETBR. Moreover, rendomab-B1 was able to disrupt the autocrine ET1-mediated survival loop on vascular endothelial cells, suggesting that this antibody could be used to prevent the pro-tumorigenic effect due to ET-1 and ETBR upregulation in the tumor-surrounding endothelium. Furthermore, rendomab-B1 binding onto ETBR was also assessed on melanoma cell lines and revealed that a tumor-specific form of ETBR may exist, as illustrated by the poor fixation of rendomab-B1 on these cells in spite of the presence of functional ETB receptors. Together, these results present rendomab-B1 as promising agent, not only for the structural and functional study of ETBR, but also for its therapeutic modulation in the case of cancer for instance. Finally, the other 26 monoclonal antibodies, whose characterization is still ongoing, also constitute potential tools for fundamental or therapeutic applications involving ETBR. To conclude, this work has highlighted the…
landing page: https://theses.hal.science/tel-00669677
identifier: NNT: 2012PA114803
keyword: anticorps-therapeutiques
keyword: axe-endotheline
keyword: dna-immunization
keyword: endothelin-axis
keyword: gpcr
keyword: immunisation-genique
keyword: infoeu-reposemanticsdoctoralthesis
keyword: rcpg
keyword: sdvmheplife-sciences-q-biohuman-health-and-pathology
keyword: sdvsalife-sciences-q-bioagricultural-sciences
keyword: therapeutic-antibodies
keyword: theses
issued: 2026-05-28T21:18:13.349326
modified: 2026-05-28T21:18:13.349336
language: fr
contact point: Organization
  fn: CCSD

test_moissonnage_selune
type: Agent

Production and characterization of polyclonal and monoclonal antibodies targeting endothelin receptors for cancer immunotherapy
type: Distribution
format: HTML
access URL: https://theses.hal.science/tel-00669677
issued: 2026-05-28T21:18:13.377200
modified: 2026-05-28T21:18:13.280800