Abstract
A single-chain Fv antibody fragment specific for the tumor-associated Ep-CAM molecule was isolated from a semisynthetic phage display library and converted into an intact, fully human IgG1 monoclonal antibody (huMab). The purified huMab had an affinity of 5 nM and effectively mediated tumor cell killing in in vitro and in vivo assays. These experiments show that nonimmunized phage antibody display libraries can be used to obtain high-affinity, functional, and clinically applicable huMabs directed against a tumor-associated antigen.
Publication types
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Comparative Study
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Research Support, Non-U.S. Gov't
MeSH terms
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Animals
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Antibodies, Monoclonal / chemistry*
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Antibodies, Monoclonal / therapeutic use
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Antigens, Neoplasm / immunology*
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Antineoplastic Agents / chemistry*
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Antineoplastic Agents / therapeutic use
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Bacteriophages / genetics
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Blotting, Western
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Cell Adhesion Molecules / immunology*
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Cell Count
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Colonic Neoplasms / drug therapy*
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Dose-Response Relationship, Drug
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Electrophoresis, Polyacrylamide Gel
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Epithelial Cell Adhesion Molecule
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Flow Cytometry
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Gene Library
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Granulocyte Colony-Stimulating Factor / metabolism
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Humans
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Immunoglobulin Fragments / chemistry*
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Immunohistochemistry
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Leukocytes, Mononuclear / drug effects
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Mice
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Mice, Inbred BALB C
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Mice, Nude
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Molecular Biology / methods*
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Neutrophils / drug effects
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Recombinant Proteins / chemistry
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Recombinant Proteins / therapeutic use
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Time Factors
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Transfection
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Tumor Cells, Cultured
Substances
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Antibodies, Monoclonal
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Antigens, Neoplasm
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Antineoplastic Agents
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Cell Adhesion Molecules
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Epithelial Cell Adhesion Molecule
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Immunoglobulin Fragments
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Recombinant Proteins
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immunoglobulin Fv
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Granulocyte Colony-Stimulating Factor