title: Design of humanized antibodies: from anti-Tac to Zenapax.
abstract: Since the introduction of hybridoma technology, monoclonal antibodies have become one of the most important tools in the biosciences, finding diverse applications including their use in the therapy of human disease. Initial attempts to use monoclonal antibodies as therapeutics were hampered, however, by the potent immunogenicity of mouse (and other rodent) antibodies in humans. Humanization technology has made it possible to remove the immunogenicity associated with the use of rodent antibodies, or at least to reduce it to an acceptable level for clinical use in humans, thus facilitating the application of monoclonal antibodies to the treatment of human disease. To date, nine humanized monoclonal antibodies have been approved for use as human therapeutics in the United States. In this paper, we describe procedures for antibody humanization with an emphasis on strategies for designing humanized antibodies with the aid of computer-guided modeling of antibody variable domains, using as an example the humanized anti-CD25 monoclonal antibody, Zenapax.
authors.affiliation: Protein Design Labs, Inc., 34801 Campus Drive, Fremont, CA 94555, USA. ntsurushita@pdl.com
authors.forename: Naoya
authors.initials: N
authors.lastname: Tsurushita
authors.forename: Paul R
authors.initials: PR
authors.lastname: Hinton
authors.forename: Shankar
authors.initials: S
authors.lastname: Kumar
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D000911:Antibodies, Monoclonal / Q000096:biosynthesis / Q000737:chemistry* / Q000235:genetics; D061067:Antibodies, Monoclonal, Humanized; D001483:Base Sequence; D000077561:Daclizumab; D006801:Humans; D007074:Immunoglobulin G / Q000096:biosynthesis / Q000737:chemistry* / Q000235:genetics; D007135:Immunoglobulin Variable Region / Q000235:genetics; D051379:Mice; D008969:Molecular Sequence Data; D015202:Protein Engineering / Q000379:methods*; D017434:Protein Structure, Tertiary; D016415:Sequence Alignment
chemical_list: D000911:Antibodies, Monoclonal; D061067:Antibodies, Monoclonal, Humanized; D007074:Immunoglobulin G; D007135:Immunoglobulin Variable Region; D000077561:Daclizumab