title: Immunoglobulin isotype knowledge and application to Fc engineering.
abstract: Monoclonal antibody-based drugs continue to be one of the most rapidly growing classes of therapeutic molecules. At present, the majority of approved therapeutic antibodies are of the human IgG1 format, which can elicit immune effector functions (e.g., antibody-dependent cellular cytotoxicity, antibody-dependent cellular phagocytosis, and complement-dependent cytotoxicity). However, there is a wealth of functional diversity that is present in other isotypes and IgG subclasses that can be exploited to improve clinical safety and performance by increasing stability, reduction of adverse events, modulation of effector functions, and by the engagement of two antigens by a single antibody. This review presents an overview of the different antibody isotypes and subclasses and details how exchanging amino acids between different isotypes (i.e., 'cross-isotypes') can be exploited to generate novel therapeutic platforms.
authors.affiliation: Genentech, Antibody Engineering, South San Francisco, CA 94080, USA. Electronic address: brezski.randall@gene.com.
authors.forename: Randall J
authors.initials: RJ
authors.lastname: Brezski
authors.affiliation: Department of Chemical Engineering, University of Texas at Austin, Austin, TX 78731, USA; Department of Molecular Biosciences, University of Texas at Austin, Austin, TX 78731, USA; Institute of Cell and Molecular Biology, University of Texas at Austin, Austin, TX 78731, USA.
authors.forename: George
authors.initials: G
authors.lastname: Georgiou
mesh_terms: D000818:Animals; D018033:Antibodies, Bispecific / Q000235:genetics / Q000627:therapeutic use*; D000911:Antibodies, Monoclonal / Q000235:genetics / Q000627:therapeutic use*; D000920:Antibody-Dependent Cell Cytotoxicity; D005818:Genetic Engineering; D006801:Humans; D007141:Immunoglobulin Fc Fragments / Q000235:genetics*; D007132:Immunoglobulin Isotypes / Q000235:genetics*; D007167:Immunotherapy / Q000379:methods* / Q000639:trends; D010587:Phagocytosis
chemical_list: D018033:Antibodies, Bispecific; D000911:Antibodies, Monoclonal; D007141:Immunoglobulin Fc Fragments; D007132:Immunoglobulin Isotypes