title: Anti-Gb3 monoclonal antibody inhibits angiogenesis and tumor development.
abstract: Inhibiting the growth of tumor vasculature represents one of the relevant strategies against tumor progression. Between all the different pro-angiogenic molecular targets, plasma membrane glycosphingolipids have been under-investigated. In this present study, we explore the anti-angiogenic therapeutic advantage of a tumor immunotherapy targeting the globotriaosylceramide Gb3. In this purpose, a monoclonal antibody against Gb3, named 3E2 was developed and characterized. We first demonstrate that Gb3 is over-expressed in proliferative endothelial cells relative to quiescent cells. Then, we demonstrate that 3E2 inhibits endothelial cell proliferation in vitro by slowing endothelial cell proliferation and by increasing mitosis duration. Antibody 3E2 is further effective in inhibiting ex vivo angiogenesis in aorta ring assays. Moreover, 3E2 treatment inhibits NXS2 neuroblastoma development and liver metastases spreading in A/J mice. Immunohistology examination of the NXS2 metastases shows that only endothelial cells, but not cancer cells express Gb3. Finally, 3E2 treatment diminishes tumor vessels density, proving a specific therapeutic action of our monoclonal antibody to tumor vasculature. Our study demonstrates that Gb3 is a viable alternative target for immunotherapy and angiogenesis inhibition.
authors.affiliation: Inserm, UMR892, Nantes, France.
authors.forename: Ariane
authors.initials: A
authors.lastname: Desselle
authors.forename: Tanguy
authors.initials: T
authors.lastname: Chaumette
authors.forename: Marie-Hélène
authors.initials: MH
authors.lastname: Gaugler
authors.forename: Denis
authors.initials: D
authors.lastname: Cochonneau
authors.forename: Julien
authors.initials: J
authors.lastname: Fleurence
authors.forename: Nolwenn
authors.initials: N
authors.lastname: Dubois
authors.forename: Philippe
authors.initials: P
authors.lastname: Hulin
authors.forename: Jacques
authors.initials: J
authors.lastname: Aubry
authors.forename: Stéphane
authors.initials: S
authors.lastname: Birklé
authors.forename: François
authors.initials: F
authors.lastname: Paris
mesh_terms: D020533:Angiogenesis Inhibitors / Q000008:administration & dosage / Q000494:pharmacology*; D000818:Animals; D000911:Antibodies, Monoclonal / Q000008:administration & dosage / Q000276:immunology* / Q000494:pharmacology*; D015295:Antigens, Tumor-Associated, Carbohydrate / Q000276:immunology* / Q000378:metabolism; D000970:Antineoplastic Agents / Q000008:administration & dosage / Q000494:pharmacology*; D002460:Cell Line; D045744:Cell Line, Tumor; D002462:Cell Membrane / Q000276:immunology / Q000378:metabolism; D049109:Cell Proliferation; D002471:Cell Transformation, Neoplastic / Q000187:drug effects* / Q000276:immunology*; D004195:Disease Models, Animal; D061307:Human Umbilical Vein Endothelial Cells / Q000276:immunology / Q000378:metabolism; D006801:Humans; D008297:Male; D051379:Mice; D009362:Neoplasm Metastasis; D009389:Neovascularization, Pathologic / Q000188:drug therapy / Q000276:immunology*; D018919:Neovascularization, Physiologic / Q000187:drug effects; D009447:Neuroblastoma / Q000188:drug therapy / Q000276:immunology / Q000473:pathology; D047368:Tumor Burden / Q000187:drug effects
chemical_list: D020533:Angiogenesis Inhibitors; D000911:Antibodies, Monoclonal; D015295:Antigens, Tumor-Associated, Carbohydrate; D000970:Antineoplastic Agents; C472766:Gb3 antigen