Abstract
Targeting tumour neovasculature using antibodies to the endothelial receptor CD105 (endoglin), is a potentially useful approach for anti-tumour therapy. We report on the preparation and the cytotoxicity of a novel immunotoxin consisting in the non-toxic type 2 ribosome-inactivating protein (RIP) nigrin b linked to the monoclonal anti-human CD105 (hCD105) antibody 44G4. The immunotoxin kills specifically mouse fibroblasts expressing the biomarker CD105 (L929-hCD105+ cells) with an IC(50) value of 6x10(-10)M while nigrin b does it at 2.4x10(-7)M. Immunofluorescence analysis indicated that the immunotoxin accumulates in a perinuclear region. In contrast, 44G4 showed a specific localization on the cell surface.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Animals
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Antigens, CD / immunology
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Biomarkers, Tumor / immunology*
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Cell Survival
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Cells, Cultured
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Endoglin
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Female
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Fibroblasts / drug effects*
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Fibroblasts / metabolism
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Flow Cytometry
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Fluorescent Antibody Technique
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Humans
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Immunotoxins / pharmacology*
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Mice
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Mice, Inbred BALB C
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N-Glycosyl Hydrolases / pharmacology*
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Neovascularization, Pathologic / drug therapy*
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Neovascularization, Pathologic / metabolism
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Plant Proteins / pharmacology*
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Protein Synthesis Inhibitors / pharmacology*
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Receptors, Cell Surface / immunology
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Ribosome Inactivating Proteins, Type 2
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Ribosomes / drug effects
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Ribosomes / metabolism
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Umbilical Veins / cytology
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Umbilical Veins / drug effects
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Umbilical Veins / metabolism
Substances
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Antigens, CD
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Biomarkers, Tumor
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ENG protein, human
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Endoglin
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Immunotoxins
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Plant Proteins
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Protein Synthesis Inhibitors
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Receptors, Cell Surface
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Ribosome Inactivating Proteins, Type 2
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N-Glycosyl Hydrolases