The neonatal Fc receptor, FcRn, as a target for drug delivery and therapy

Adv Drug Deliv Rev. 2015 Aug 30:91:109-24. doi: 10.1016/j.addr.2015.02.005. Epub 2015 Feb 19.

Abstract

Immunoglobulin G (IgG)-based drugs are arguably the most successful class of protein therapeutics due in part to their remarkably long blood circulation. This arises from IgG interaction with the neonatal Fc receptor, FcRn. FcRn is the central regulator of IgG and albumin homeostasis throughout life and is increasingly being recognized as an important player in autoimmune disease, mucosal immunity, and tumor immune surveillance. Various engineering approaches that hijack or disrupt the FcRn-mediated transport pathway have been devised to develop long-lasting and non-invasive protein therapeutics, protein subunit vaccines, and therapeutics for treatment of autoimmune and infectious disease. In this review, we highlight the diverse biological functions of FcRn, emerging therapeutic opportunities, as well as the associated challenges of targeting FcRn for drug delivery and disease therapy.

Keywords: Albumin; FcRn; Immunoglobulin G; Nanoparticle; Protein engineering.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Animals
  • Autoimmune Diseases / drug therapy
  • Autoimmune Diseases / immunology
  • Biological Transport / drug effects
  • Communicable Diseases / drug therapy
  • Communicable Diseases / immunology
  • Drug Delivery Systems*
  • Histocompatibility Antigens Class I / immunology
  • Histocompatibility Antigens Class I / metabolism*
  • Humans
  • Immunity, Mucosal
  • Immunoglobulin G / immunology*
  • Receptors, Fc / immunology
  • Receptors, Fc / metabolism*

Substances

  • Histocompatibility Antigens Class I
  • Immunoglobulin G
  • Receptors, Fc
  • Fc receptor, neonatal