Neonatal Fc receptor and IgG-based therapeutics

MAbs. Sep-Oct 2011;3(5):422-30. doi: 10.4161/mabs.3.5.16983. Epub 2011 Sep 1.

Abstract

The majority of potent new biologics today are IgG-based molecules that have demonstrated tissue-targeting specificity with favorable clinical response. Several factors determine the efficacy of these products, including target specificity, serum half-life and effector functions via complement-dependent cytotoxicity, antibody-dependent cell-mediated cytotoxicity or drug conjugates. In this review, we will focus on the interaction between therapeutic antibody and neonatal Fc receptor (FcRn), which is one of the critical factors in determining the circulating antibody half-life. Specifically, we will review the fundamental biology of FcRn, FcRn functions in various organs, Fc mutations designed to modulate binding to FcRn, IgG-based therapeutics that directly exploit FcRn functions and tools and strategies used to study FcRn-IgG interactions. Comprehensive understanding of FcRn-IgG interactions not only allows for development of effective therapeutics, but also avoidance of potential adverse effects.

Publication types

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

MeSH terms

  • Animals
  • Antibody Affinity / immunology
  • Autoimmune Diseases / immunology
  • Autoimmune Diseases / therapy*
  • Histocompatibility Antigens Class I / metabolism*
  • Humans
  • Immunoglobulin Fc Fragments / genetics
  • Immunoglobulin Fc Fragments / immunology
  • Immunoglobulin G / immunology
  • Immunoglobulin G / metabolism
  • Immunoglobulin G / therapeutic use*
  • Mice
  • Models, Molecular
  • Rabbits
  • Receptors, Fc / metabolism*

Substances

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