Production of a mouse-human chimeric monoclonal antibody to CD20 with potent Fc-dependent biologic activity

• Published in: The Journal of immunology (1950) Vol. 139; no. 10; pp. 3521 - 3526
• Main Authors: Liu, AY, Robinson, RR, Murray, ED, Jr, Ledbetter, JA, Hellstrom, I, Hellstrom, KE
• Format: Journal Article
• Language: English
• Published: Bethesda, MD Am Assoc Immnol 15.11.1987; American Association of Immunologists
• Subjects: Amino Acid Sequence; Animals; Antibodies, Monoclonal - genetics; Antibodies, Monoclonal - immunology; Antibody-Dependent Cell Cytotoxicity; Antigens, Differentiation, B-Lymphocyte - immunology; Antigens, Neoplasm - immunology; Applied sciences; B-Lymphocytes - immunology; Base Sequence; Cytotoxicity Tests, Immunologic; DNA - genetics; DNA, Recombinant; Exact sciences and technology; Humans; Immunoglobulin Constant Regions - genetics; Immunoglobulin Fc Fragments - immunology; Immunoglobulin G - genetics; Immunoglobulin G - immunology; Immunoglobulin kappa-Chains - genetics; Immunoglobulin kappa-Chains - immunology; Mice; Molecular Sequence Data; Other techniques and industries; Recombinant Proteins - immunology
• ISSN: 0022-1767; 1550-6606
• DOI: 10.4049/jimmunol.139.10.3521

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.