Abstract
Antibodies can be conjugated to effector molecules to derive targeted therapeutics with properties such as cell-specific cytotoxicity. The murine anti-CD22 antibody RFB4 linked to a member of the ribonuclease A superfamily, Onconase (Onc), becomes a potential drug candidate for non-Hodgkin's lymphoma. Onc is currently in Phase III clinical trials for unresectable malignant mesothelioma but conjugation to RFB4 considerably enhances its specificity for CD22+ lymphomas. RFB4-targeted Onc is effective in preclinical models, causes little non-specific toxicities in mice, and has favorable formulation properties. Derivatization and conjugation of RFB4 and Onc have been optimized.
Publication types
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Research Support, N.I.H., Extramural
MeSH terms
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Animals
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Antibodies, Monoclonal / immunology*
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Antibodies, Monoclonal / isolation & purification
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Antineoplastic Agents / pharmacology
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Cell Death / drug effects
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Cell Line, Tumor
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Disulfides / metabolism
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Drug Screening Assays, Antitumor
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Flow Cytometry
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Fluorescent Antibody Technique
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Humans
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Mice
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Molecular Biology / methods*
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RNA, Transfer / metabolism
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Recombinant Fusion Proteins / metabolism
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Recombinant Fusion Proteins / pharmacology
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Ribonucleases / biosynthesis*
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Ribonucleases / immunology*
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Ribonucleases / isolation & purification
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Sialic Acid Binding Ig-like Lectin 2 / immunology*
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Succinimides
Substances
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Antibodies, Monoclonal
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Antineoplastic Agents
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Disulfides
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Recombinant Fusion Proteins
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Sialic Acid Binding Ig-like Lectin 2
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Succinimides
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N-succinimidyl 3-(2-pyridyldithio)propionate
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RNA, Transfer
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Ribonucleases
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ranpirnase