The humanized anti-HM1.24 antibody effectively kills multiple myeloma cells by human effector cell-mediated cytotoxicity.
A mouse monoclonal antibody, anti-HM1.24 (IgG2a/kappa), binds to a surface antigen preferentially overexpressed on multiple myeloma (MM) cells, and exhibits potent antitumor cell activity against MM cells by antibody-dependent cell-mediated cytotoxicity (ADCC). To develop an antibody-based immunotherapy against MM, a humanized anti-HM1.24 antibody, in which all FRs correspond to naturally processed human FRs, has been successfully constructed with the aid of both the hybrid variable region and two-step design methods. This humanized anti-HM1.24 antibody (IgG1/kappa) is able to effectively induce ADCC against human myeloma KPMM2 and ARH77 cells in the presence of human PBMCs as effectively as a chimeric anti-HM1.24 antibody. The humanized anti-HM1.24 antibody, therefore, could be expected as a potent immunotherapeutic agent for MM patients.
Ono
K
K
Chugai Pharmaceutical Co Ltd, Fuji-Gotemba Research Labs, Shizuoka, Japan.
Ohtomo
T
T
Yoshida
K
K
Yoshimura
Y
Y
Kawai
S
S
Koishihara
Y
Y
Ozaki
S
S
Kosaka
M
M
Tsuchiya
M
M
D000595:Amino Acid Sequence; D000818:Animals; D000906:Antibodies / Q000627:therapeutic use*; D000920:Antibody-Dependent Cell Cytotoxicity; D015703:Antigens, CD; D000970:Antineoplastic Agents / Q000627:therapeutic use*; D019556:COS Cells; D002478:Cells, Cultured; D004354:Drug Screening Assays, Antitumor; D004797:Enzyme-Linked Immunosorbent Assay; D058851:GPI-Linked Proteins; D006801:Humans; D007135:Immunoglobulin Variable Region / Q000235:genetics / Q000276:immunology; D008562:Membrane Glycoproteins / Q000276:immunology*; D051379:Mice; D008969:Molecular Sequence Data; D009101:Multiple Myeloma / Q000628:therapy*; D011993:Recombinant Fusion Proteins / Q000276:immunology / Q000627:therapeutic use; D017386:Sequence Homology, Amino Acid; D014407:Tumor Cells, Cultured; D000074010:Bone Marrow Stromal Antigen 2
D000906:Antibodies; D015703:Antigens, CD; D000970:Antineoplastic Agents; D058851:GPI-Linked Proteins; D007135:Immunoglobulin Variable Region; D008562:Membrane Glycoproteins; D011993:Recombinant Fusion Proteins; C094572:BST2 protein, human; D000074010:Bone Marrow Stromal Antigen 2