Reshaping a human antibody to inhibit the interleukin 6-dependent tumor cell growth

Cancer Res. 1993 Feb 15;53(4):851-6.


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

  • Amino Acid Sequence
  • Animals
  • Antibodies, Monoclonal / chemistry*
  • Antibodies, Monoclonal / immunology
  • Antibodies, Monoclonal / metabolism
  • Cell Division
  • Humans
  • Immunoglobulin Heavy Chains / chemistry*
  • Immunoglobulin Heavy Chains / immunology
  • Immunoglobulin Light Chains / chemistry*
  • Immunoglobulin Light Chains / immunology
  • Immunoglobulin Variable Region / chemistry*
  • Immunoglobulin Variable Region / immunology
  • Immunotherapy
  • Interleukin-6 / immunology*
  • Interleukin-6 / therapeutic use
  • Mice
  • Molecular Sequence Data
  • Multiple Myeloma / therapy
  • Receptors, Immunologic / immunology*
  • Receptors, Immunologic / metabolism
  • Receptors, Interleukin-6
  • Recombinant Fusion Proteins / chemistry
  • Recombinant Fusion Proteins / immunology


  • Antibodies, Monoclonal
  • Immunoglobulin Heavy Chains
  • Immunoglobulin Light Chains
  • Immunoglobulin Variable Region
  • Interleukin-6
  • Receptors, Immunologic
  • Receptors, Interleukin-6
  • Recombinant Fusion Proteins