Reshaping a human antibody to inhibit the interleukin 6-dependent tumor cell growth.
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.
Sato
K
K
Fuji-Gotemba Research Laboratories, Chugai Pharmaceutical, Co., Ltd., Shizuoka, Japan.
Tsuchiya
M
M
Saldanha
J
J
Koishihara
Y
Y
Ohsugi
Y
Y
Kishimoto
T
T
Bendig
M M
MM
D000595:Amino Acid Sequence; D000818:Animals; D000911:Antibodies, Monoclonal / Q000737:chemistry* / Q000276:immunology / Q000378:metabolism; D002455:Cell Division; D006801:Humans; D007143:Immunoglobulin Heavy Chains / Q000737:chemistry* / Q000276:immunology; D007147:Immunoglobulin Light Chains / Q000737:chemistry* / Q000276:immunology; D007135:Immunoglobulin Variable Region / Q000737:chemistry* / Q000276:immunology; D007167:Immunotherapy; D015850:Interleukin-6 / Q000276:immunology* / Q000627:therapeutic use; D051379:Mice; D008969:Molecular Sequence Data; D009101:Multiple Myeloma / Q000628:therapy; D011971:Receptors, Immunologic / Q000276:immunology* / Q000378:metabolism; D019947:Receptors, Interleukin-6; D011993:Recombinant Fusion Proteins / Q000737:chemistry / Q000276:immunology
D000911:Antibodies, Monoclonal; D007143:Immunoglobulin Heavy Chains; D007147:Immunoglobulin Light Chains; D007135:Immunoglobulin Variable Region; D015850:Interleukin-6; D011971:Receptors, Immunologic; D019947:Receptors, Interleukin-6; D011993:Recombinant Fusion Proteins