Production of a mouse-human chimeric monoclonal antibody to CD20 with potent Fc-dependent biologic activity.
Mouse monoclonal antibody 2H7 recognizes the CD20 cell surface phosphoprotein that is expressed in normal as well as malignant B cells. CD20 may be a useful target for therapy of B cell lymphomas, since damaged normal B cells can be replaced by their antigen-negative precursors. Monoclonal antibody 2H7 is an IgG2b (kappa) immunoglobulin which cannot mediate antibody-dependent cellular cytotoxicity with human lymphocytes or complement-dependent cytotoxicity with human serum. We have now generated a chimeric 2H7 antibody by substituting the mouse constant domains of 2H7 with the human gamma 1 and kappa domains. This new antibody has the same binding specificities as 2H7 but is highly effective in mediating antibody-dependent cellular cytotoxicity with human effector cells and complement-dependent cytotoxicity with human complement.
D000595:Amino Acid Sequence; D000818:Animals; D000911:Antibodies, Monoclonal / Q000235:genetics / Q000276:immunology*; D000920:Antibody-Dependent Cell Cytotoxicity; D000944:Antigens, Differentiation, B-Lymphocyte / Q000276:immunology*; D000951:Antigens, Neoplasm / Q000276:immunology; D001402:B-Lymphocytes / Q000276:immunology*; D001483:Base Sequence; D003601:Cytotoxicity Tests, Immunologic; D004247:DNA / Q000235:genetics; D004274:DNA, Recombinant; D006801:Humans; D007127:Immunoglobulin Constant Regions / Q000235:genetics; D007141:Immunoglobulin Fc Fragments / Q000276:immunology*; D007074:Immunoglobulin G / Q000235:genetics / Q000276:immunology; D007145:Immunoglobulin kappa-Chains / Q000235:genetics / Q000276:immunology; D051379:Mice; D008969:Molecular Sequence Data; D011994:Recombinant Proteins / Q000276:immunology*
D000911:Antibodies, Monoclonal; D000944:Antigens, Differentiation, B-Lymphocyte; D000951:Antigens, Neoplasm; D004274:DNA, Recombinant; D007127:Immunoglobulin Constant Regions; D007141:Immunoglobulin Fc Fragments; D007074:Immunoglobulin G; D007145:Immunoglobulin kappa-Chains; D011994:Recombinant Proteins; D004247:DNA