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.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Animals
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Antibodies, Monoclonal, Murine-Derived / pharmacology*
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Antigens, CD / genetics
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Antigens, CD / metabolism*
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Antineoplastic Combined Chemotherapy Protocols / pharmacology
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Colonic Neoplasms / blood supply
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Colonic Neoplasms / drug therapy
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Colonic Neoplasms / genetics
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Colonic Neoplasms / metabolism
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Colonic Neoplasms / pathology
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Corneal Neovascularization / drug therapy
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Corneal Neovascularization / genetics
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Corneal Neovascularization / metabolism
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Corneal Neovascularization / pathology
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Cyclophosphamide / pharmacology
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Female
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Fibroblast Growth Factor 2 / genetics
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Fibroblast Growth Factor 2 / metabolism
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GPI-Linked Proteins / genetics
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GPI-Linked Proteins / metabolism
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Humans
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Male
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Melanoma / blood supply
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Melanoma / drug therapy
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Melanoma / genetics
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Melanoma / metabolism
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Melanoma / pathology
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Mice
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Mice, Inbred BALB C
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Mice, Nude
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Neovascularization, Pathologic / drug therapy*
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Neovascularization, Pathologic / genetics
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Neovascularization, Pathologic / metabolism
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Neovascularization, Pathologic / pathology
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Rabbits
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Receptors, Immunologic / genetics
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Receptors, Immunologic / metabolism*
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Retinal Diseases / drug therapy
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Retinal Diseases / genetics
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Retinal Diseases / metabolism
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Retinal Diseases / pathology
Substances
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Antibodies, Monoclonal, Murine-Derived
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Antigens, CD
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CD160 protein, human
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Cd160 protein, mouse
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GPI-Linked Proteins
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Receptors, Immunologic
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Fibroblast Growth Factor 2
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Cyclophosphamide