Abstract
The mouse PM-1 monoclonal antibody binds to the human interleukin 6 receptor, inhibits IL-6 functions, and shows strong antitumor cell activity against multiple myeloma cells. In order to be effective as a therapeutic agent administered to human patients in repeated doses, reshaped human PM-1 antibodies consisting of human REI-based light chain and NEW-based heavy chain variable regions were designed and constructed with the assistance of a structural model of the mouse PM-1 variable regions. The best reshaped human PM-1 antibody is equivalent to mouse or chimeric PM-1 antibody in terms of antigen binding and growth inhibition against multiple myeloma cells. Only a few minor changes in the human framework regions were required to recreate the mouse PM-1 antigen-binding site within a human antibody. The reshaped human PM-1 antibody, therefore, could be efficacious in human multiple myeloma patients.
MeSH terms
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Amino Acid Sequence
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Animals
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Antibodies, Monoclonal / chemistry*
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Antibodies, Monoclonal / immunology
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Antibodies, Monoclonal / metabolism
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Cell Division
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Humans
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Immunoglobulin Heavy Chains / chemistry*
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Immunoglobulin Heavy Chains / immunology
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Immunoglobulin Light Chains / chemistry*
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Immunoglobulin Light Chains / immunology
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Immunoglobulin Variable Region / chemistry*
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Immunoglobulin Variable Region / immunology
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Immunotherapy
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Interleukin-6 / immunology*
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Interleukin-6 / therapeutic use
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Mice
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Molecular Sequence Data
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Multiple Myeloma / therapy
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Receptors, Immunologic / immunology*
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Receptors, Immunologic / metabolism
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Receptors, Interleukin-6
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Recombinant Fusion Proteins / chemistry
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Recombinant Fusion Proteins / immunology
Substances
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Antibodies, Monoclonal
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Immunoglobulin Heavy Chains
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Immunoglobulin Light Chains
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Immunoglobulin Variable Region
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Interleukin-6
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Receptors, Immunologic
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Receptors, Interleukin-6
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Recombinant Fusion Proteins