title: Engineering of therapeutic antibodies to minimize immunogenicity and optimize function.
abstract: One of the first difficulties in developing monoclonal antibody therapeutics was the recognition that human anti-mouse antibody (HAMA) response limited the administration of murine antibodies. Creative science has lead to a number of ways to counter the immunogenicity of non-human antibodies, primarily through chimeric, humanized, de-immunized, and most recently, human-sequence therapeutic antibodies. Once therapeutic antibodies of low or no immunogenicity were available, the creativity then turned to engineering both the antigen-binding domains (e.g., affinity maturation, stability) and altering the effector functions (e.g. antibody-dependent cellular cytotoxicity, complement-dependent cellular cytotoxicity, and clearance rate).
authors.affiliation: Department of Protein engineering, Schering-Plough Biopharma, 901 California Avenue, Palo Alto, CA 94304, USA. leonard.presta@spcorp.com
authors.forename: Leonard G
authors.initials: LG
authors.lastname: Presta
mesh_terms: D000818:Animals; D000906:Antibodies / Q000737:chemistry / Q000276:immunology* / Q000627:therapeutic use*; D000888:Antibodies, Anti-Idiotypic / Q000096:biosynthesis / Q000276:immunology; D000920:Antibody-Dependent Cell Cytotoxicity; D015922:Complement C1q / Q000276:immunology; D006801:Humans; D051379:Mice; D008822:Mice, Transgenic; D015202:Protein Engineering; D013045:Species Specificity
chemical_list: D000906:Antibodies; D000888:Antibodies, Anti-Idiotypic; D015922:Complement C1q