title: A novel antiangiogenic and vascular normalization therapy targeted against human CD160 receptor.
abstract: Angiogenesis plays an essential role in several diseases of the eye and in the growth of solid tumors, but existing antiangiogenic therapies have limited benefits in several cases. We report the antiangiogenic effects of a monoclonal antibody, CL1-R2, in several animal models of neovascularization. CL1-R2 recognizes human CD160, a membrane receptor which is conserved in various mammal species. We show that CD160 is expressed on the endothelial cells of newly formed blood vessels in human colon carcinoma and mouse B16 melanoma but not in vessels of healthy tissues. CL1-R2 reduced fibroblast growth factor 2-induced neovascularization in the rabbit cornea, in a mouse model of oxygen-induced retinopathy, and in a mouse Matrigel plug assay. Treatment of B16 melanoma-bearing mice with CL1-R2 combined with cyclophosphamide chemotherapy caused regression of the tumor vasculature and normalization of the remaining vessels as shown by Doppler ultrasonography, intravital microscopy, and histology. These studies validate CD160 as a potential new target in cases of human pathological ocular and tumor neoangiogenesis that do not respond or become resistant to existing antiangiogenic drugs.
authors.affiliation: Institut National de la Santé et de la Recherche Médicale U1043, F-31300 Toulouse, France.
authors.forename: Sophie
authors.initials: S
authors.lastname: Chabot
authors.forename: Nabila
authors.initials: N
authors.lastname: Jabrane-Ferrat
authors.forename: Karine
authors.initials: K
authors.lastname: Bigot
authors.forename: Julie
authors.initials: J
authors.lastname: Tabiasco
authors.forename: Alexandra
authors.initials: A
authors.lastname: Provost
authors.forename: Muriel
authors.initials: M
authors.lastname: Golzio
authors.forename: Muhammad Zaeem
authors.initials: MZ
authors.lastname: Noman
authors.forename: Jérôme
authors.initials: J
authors.lastname: Giustiniani
authors.forename: Elisabeth
authors.initials: E
authors.lastname: Bellard
authors.forename: Stéphanie
authors.initials: S
authors.lastname: Brayer
authors.forename: Maryse
authors.initials: M
authors.lastname: Aguerre-Girr
authors.forename: Fabienne
authors.initials: F
authors.lastname: Meggetto
authors.forename: Sylvie
authors.initials: S
authors.lastname: Giuriato
authors.forename: François
authors.initials: F
authors.lastname: Malecaze
authors.forename: Stéphane
authors.initials: S
authors.lastname: Galiacy
authors.forename: Jean-Philippe
authors.initials: JP
authors.lastname: Jaïs
authors.forename: Olivier
authors.initials: O
authors.lastname: Chose
authors.forename: Jean
authors.initials: J
authors.lastname: Kadouche
authors.forename: Salem
authors.initials: S
authors.lastname: Chouaib
authors.forename: Justin
authors.initials: J
authors.lastname: Teissié
authors.forename: Marc
authors.initials: M
authors.lastname: Abitbol
authors.forename: Armand
authors.initials: A
authors.lastname: Bensussan
authors.forename: Philippe
authors.initials: P
authors.lastname: Le Bouteiller
mesh_terms: D000818:Animals; D058846:Antibodies, Monoclonal, Murine-Derived / Q000494:pharmacology*; D015703:Antigens, CD / Q000235:genetics / Q000378:metabolism*; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000494:pharmacology; D003110:Colonic Neoplasms / Q000098:blood supply / Q000188:drug therapy / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D016510:Corneal Neovascularization / Q000188:drug therapy / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D003520:Cyclophosphamide / Q000494:pharmacology; D005260:Female; D016222:Fibroblast Growth Factor 2 / Q000235:genetics / Q000378:metabolism; D058851:GPI-Linked Proteins / Q000235:genetics / Q000378:metabolism; D006801:Humans; D008297:Male; D008545:Melanoma / Q000098:blood supply / Q000188:drug therapy / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D051379:Mice; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D009389:Neovascularization, Pathologic / Q000188:drug therapy* / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D011817:Rabbits; D011971:Receptors, Immunologic / Q000235:genetics / Q000378:metabolism*; D012164:Retinal Diseases / Q000188:drug therapy / Q000235:genetics / Q000378:metabolism / Q000473:pathology
chemical_list: D058846:Antibodies, Monoclonal, Murine-Derived; D015703:Antigens, CD; C114505:CD160 protein, human; C511585:Cd160 protein, mouse; D058851:GPI-Linked Proteins; D011971:Receptors, Immunologic; D016222:Fibroblast Growth Factor 2; D003520:Cyclophosphamide