Reshaping a human antibody to inhibit the interleukin 6-dependent tumor cell growth.
basic_science · Level V
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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.
Medical subject headings
- Antibodies, Monoclonal
- Immunoglobulin Heavy Chains
- Immunoglobulin Light Chains
- Immunoglobulin Variable Region
- Interleukin-6
- Receptors, Immunologic