Fc fusion as a platform technology: potential for modulating immunogenicity

Ditza Levin; Basil Golding; Scott E Strome; Zuben E Sauna

doi:10.1016/j.tibtech.2014.11.001

Fc fusion as a platform technology: potential for modulating immunogenicity

Trends Biotechnol. 2015 Jan;33(1):27-34. doi: 10.1016/j.tibtech.2014.11.001. Epub 2014 Dec 6.

Authors

Ditza Levin¹, Basil Golding², Scott E Strome³, Zuben E Sauna⁴

Affiliations

¹ 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.
² 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.
³ Department of Otorhinolaryngology-Head and Neck Surgery, University of Maryland School of Medicine, 16 South Eutaw Street Suite 500, Baltimore, MD 21201, USA.
⁴ 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.

PMID: 25488117
DOI: 10.1016/j.tibtech.2014.11.001

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.

Keywords: Fc receptors; Fc-fusion technology; drug development; immunogenicity; neutralizing antidrug antibodies; therapeutic proteins.

Published by Elsevier Ltd.

Publication types

Research Support, Non-U.S. Gov't
Research Support, U.S. Gov't, Non-P.H.S.
Review

MeSH terms

Antibodies, Monoclonal / chemistry*
Autoimmune Diseases / drug therapy
Drug Delivery Systems
Humans
Immunoglobulin Fc Fragments / therapeutic use
Immunomodulation / drug effects
Models, Immunological
Protein Engineering / methods*
Recombinant Fusion Proteins / therapeutic use

Substances

Antibodies, Monoclonal
Immunoglobulin Fc Fragments
Recombinant Fusion Proteins