title: Boosting ADCC and CDC activity by Fc engineering and evaluation of antibody effector functions.
abstract: In recent years, therapy with monoclonal antibodies has become standard of care in various clinical applications. Despite obvious clinical activity, not all patients respond and benefit from this generally well tolerated treatment option. Therefore, rational optimization of antibody therapy represents a major area of interest in translational research. Animal models and clinical data suggested important roles of Fc-mediated effector mechanisms such as antibody dependent cell-mediated cytotoxicity (ADCC) or complement dependent cytotoxicity (CDC) in antibody therapy. These novel insights into the mechanisms of action mediated by monoclonal antibodies inspired the development of different engineering approaches to enhance/optimize antibodies' effector functions. Fc-engineering approaches by altering the Fc-bound glycosylation profile or by exchanging amino acids in the protein backbone have been intensively studied. Here, advanced and emerging technologies in Fc-engineering resulting in altered ADCC and CDC activity are summarized and experimental strategies to evaluate antibodies' effector functions are discussed.
authors.affiliation: Division of Stem Cell Transplantation and Immunotherapy, 2nd Department of Medicine, Christian-Albrechts-University Kiel, Germany.
authors.forename: Christian
authors.initials: C
authors.lastname: Kellner
authors.affiliation: Division of Stem Cell Transplantation and Immunotherapy, 2nd Department of Medicine, Christian-Albrechts-University Kiel, Germany.
authors.forename: Stefanie
authors.initials: S
authors.lastname: Derer
authors.affiliation: Division of Stem Cell Transplantation and Immunotherapy, 2nd Department of Medicine, Christian-Albrechts-University Kiel, Germany.
authors.forename: Thomas
authors.initials: T
authors.lastname: Valerius
authors.affiliation: Division of Stem Cell Transplantation and Immunotherapy, 2nd Department of Medicine, Christian-Albrechts-University Kiel, Germany. Electronic address: m.peipp@med2.uni-kiel.de.
authors.forename: Matthias
authors.initials: M
authors.lastname: Peipp
mesh_terms: D000818:Animals; D000920:Antibody-Dependent Cell Cytotoxicity; D003165:Complement System Proteins / Q000502:physiology*; D004353:Drug Evaluation, Preclinical; D006031:Glycosylation; D006801:Humans; D007141:Immunoglobulin Fc Fragments / Q000096:biosynthesis / Q000235:genetics* / Q000494:pharmacology; D015202:Protein Engineering; D011499:Protein Processing, Post-Translational
chemical_list: D007141:Immunoglobulin Fc Fragments; D003165:Complement System Proteins
keywords: ADCC; Antibody engineering; Antibody glycosylation; Antibody therapy; CDC; Fc modification