title: Molecular engineering and design of therapeutic antibodies.
abstract: Since the first murine monoclonal antibody was approved for human therapeutic use over a decade ago, the realization that monoclonal antibody therapeutics could be engineered to improve their efficacy has inspired an astonishing array of novel antibody constructs. Early focus was on reducing the immunogenicity of rodent antibodies via humanization and generation of antibodies in transgenic mice; as those techniques were being established and then provided marketed therapeutic antibodies, the focus expanded to include engineering for enhanced effector functions, control of half-life, tumor and tissue accessibility, augmented biophysical characteristics such as stability, and more efficient (and less costly) production. Over the past two years significant progress in designing antibodies with improved pharmacokinetic properties, via modified interaction with the neonatal Fc receptor (FcRn), has been achieved. Likewise, the ability to alter the communication of a therapeutic antibody with the immune system has been advanced, using both manipulation of the immunoglobulin protein sequence and its glycosylation. Although clinical evaluation of these engineered modifications has yet to be reported, results in primates are encouraging.
authors.affiliation: Schering-Plough Biopharma, Palo Alto, CA 94304, USA. leonard.presta@spcorp.com
authors.forename: Leonard G
authors.initials: LG
authors.lastname: Presta
mesh_terms: D000818:Animals; D000911:Antibodies, Monoclonal / Q000276:immunology* / Q000378:metabolism; D000915:Antibody Affinity; D000920:Antibody-Dependent Cell Cytotoxicity; D015922:Complement C1q / Q000276:immunology* / Q000378:metabolism; D015195:Drug Design; D006207:Half-Life; D006801:Humans; D007132:Immunoglobulin Isotypes / Q000276:immunology* / Q000378:metabolism; D015202:Protein Engineering; D011961:Receptors, Fc / Q000276:immunology* / Q000378:metabolism
chemical_list: D000911:Antibodies, Monoclonal; D007132:Immunoglobulin Isotypes; D011961:Receptors, Fc; D015922:Complement C1q