title: Harnessing Fc receptor biology in the design of therapeutic antibodies.
abstract: The antibody Fc domain engages the small family of Fc receptors, expressed on cells of the immune system and beyond, to stimulate a rich diversity of positive and negative cell-mediated effector functions. The emergence of monoclonal antibodies for the treatment of various pathologic conditions has provided additional insights into Fc receptor biology, and has suggested new strategies to exploit Fc receptor interactions to create improved therapeutics. While most therapeutic IgGs approved to date have retained a native IgG Fc domain, the knowledge gained over the last decades has provided the opportunity to design tailored and more efficacious immunotherapies exhibiting fewer side effects and longer half-life. This review summarizes recent advances made in the design of biologics that modulate or exploit Fc receptor-IgG interactions, and describes innovative drugs currently under investigation in clinical trials that have been precisely tuned to achieve a desired therapeutic effect.
authors.affiliation: SuppreMol GmbH, a wholly-owned subsidiary of Baxalta Incorporated, Am Klopferspitz 19a, D-82152 Martinsried, Germany. Electronic address: peter.sondermann@baxalta.com.
authors.forename: Peter
authors.initials: P
authors.lastname: Sondermann
authors.affiliation: Xencor, Inc., 111 West Lemon Avenue, Monrovia, CA 91016, USA(1). Electronic address: david.szymkowski@xencor.com.
authors.forename: David E
authors.initials: DE
authors.lastname: Szymkowski
mesh_terms: D000818:Animals; D000911:Antibodies, Monoclonal / Q000627:therapeutic use*; D015195:Drug Design; D006801:Humans; D007141:Immunoglobulin Fc Fragments / Q000627:therapeutic use*; D007167:Immunotherapy / Q000379:methods* / Q000639:trends; D015202:Protein Engineering; D011961:Receptors, Fc / Q000235:genetics / Q000378:metabolism*; D011993:Recombinant Fusion Proteins / Q000627:therapeutic use*; D015398:Signal Transduction
chemical_list: D000911:Antibodies, Monoclonal; D007141:Immunoglobulin Fc Fragments; D011961:Receptors, Fc; D011993:Recombinant Fusion Proteins