title: Fc-fusion proteins and FcRn: structural insights for longer-lasting and more effective therapeutics.
abstract: Nearly 350 IgG-based therapeutics are approved for clinical use or are under development for many diseases lacking adequate treatment options. These include molecularly engineered biologicals comprising the IgG Fc-domain fused to various effector molecules (so-called Fc-fusion proteins) that confer the advantages of IgG, including binding to the neonatal Fc receptor (FcRn) to facilitate in vivo stability, and the therapeutic benefit of the specific effector functions. Advances in IgG structure-function relationships and an understanding of FcRn biology have provided therapeutic opportunities for previously unapproachable diseases. This article discusses approved Fc-fusion therapeutics, novel Fc-fusion proteins and FcRn-dependent delivery approaches in development, and how engineering of the FcRn-Fc interaction can generate longer-lasting and more effective therapeutics.
authors.affiliation: Division of Gastroenterology, Department of Medicine, Brigham and Women's Hospital, Harvard Medical School , Boston, MA , USA .
authors.forename: Timo
authors.initials: T
authors.lastname: Rath
authors.forename: Kristi
authors.initials: K
authors.lastname: Baker
authors.forename: Jennifer A
authors.initials: JA
authors.lastname: Dumont
authors.forename: Robert T
authors.initials: RT
authors.lastname: Peters
authors.forename: Haiyan
authors.initials: H
authors.lastname: Jiang
authors.forename: Shuo-Wang
authors.initials: SW
authors.lastname: Qiao
authors.forename: Wayne I
authors.initials: WI
authors.lastname: Lencer
authors.forename: Glenn F
authors.initials: GF
authors.lastname: Pierce
authors.forename: Richard S
authors.initials: RS
authors.lastname: Blumberg
mesh_terms: D000818:Animals; D015395:Histocompatibility Antigens Class I; D006801:Humans; D007074:Immunoglobulin G; D007167:Immunotherapy; D051379:Mice; D008958:Models, Molecular; D011961:Receptors, Fc; D011993:Recombinant Fusion Proteins
chemical_list: D015395:Histocompatibility Antigens Class I; D007074:Immunoglobulin G; D011961:Receptors, Fc; D011993:Recombinant Fusion Proteins; C100688:Fc receptor, neonatal
keywords: Fc-fusion proteins; IgG; mucosal drug delivery; neonatal Fc receptor; therapeutic antibody