Reshaping a human antibody to inhibit the interleukin 6-dependent tumor cell growth
K Sato, M Tsuchiya, J Saldanha, Y Koishihara… - Cancer research, 1993 - AACR
K Sato, M Tsuchiya, J Saldanha, Y Koishihara, Y Ohsugi, T Kishimoto, MM Bendig
Cancer research, 1993•AACRThe 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 …
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 …
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.
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