title: Fc fusion as a platform technology: potential for modulating immunogenicity.
abstract: The platform technology of fragment crystallizable (Fc) fusion, in which the Fc region of an antibody is genetically linked to an active protein drug, is among the most successful of a new generation of bioengineering strategies. Immunogenicity is a critical safety concern in the development of any protein therapeutic. While the therapeutic goal of generating Fc-fusion proteins has been to extend half-life, there is a critical mass of literature from immunology indicating that appropriate design of the Fc component has the potential to engage the immune system for product-specific outcomes. In the context of Fc-fusion therapeutics, a review of progress in understanding Fc biology suggests the prospect of engineering products that have an extended half-life and are able to modulate the immune system.
authors.affiliation: Laboratory of Hemostasis, Division of Hematology Research and Review, Center for Biologics Evaluation and Research, Food and Drug Administration, 10903 New Hampshire Avenue, Silver Spring, MD 20993, USA.
authors.forename: Ditza
authors.initials: D
authors.lastname: Levin
authors.affiliation: Plasma Derivatives, Division of Hematology Research and Review, Center for Biologics Evaluation and Research, Food and Drug Administration, 10903 New Hampshire Avenue, Silver Spring, MD 20993, USA.
authors.forename: Basil
authors.initials: B
authors.lastname: Golding
authors.affiliation: Department of Otorhinolaryngology-Head and Neck Surgery, University of Maryland School of Medicine, 16 South Eutaw Street Suite 500, Baltimore, MD 21201, USA.
authors.forename: Scott E
authors.initials: SE
authors.lastname: Strome
authors.affiliation: Laboratory of Hemostasis, Division of Hematology Research and Review, Center for Biologics Evaluation and Research, Food and Drug Administration, 10903 New Hampshire Avenue, Silver Spring, MD 20993, USA. Electronic address: zuben.sauna@fda.hhs.gov.
authors.forename: Zuben E
authors.initials: ZE
authors.lastname: Sauna
mesh_terms: D000911:Antibodies, Monoclonal / Q000737:chemistry*; D001327:Autoimmune Diseases / Q000188:drug therapy; D016503:Drug Delivery Systems; D006801:Humans; D007141:Immunoglobulin Fc Fragments / Q000627:therapeutic use; D056747:Immunomodulation / Q000187:drug effects; D018448:Models, Immunological; D015202:Protein Engineering / Q000379:methods*; D011993:Recombinant Fusion Proteins / Q000627:therapeutic use
chemical_list: D000911:Antibodies, Monoclonal; D007141:Immunoglobulin Fc Fragments; D011993:Recombinant Fusion Proteins
keywords: Fc receptors; Fc-fusion technology; drug development; immunogenicity; neutralizing antidrug antibodies; therapeutic proteins