1,814
Views
44
CrossRef citations to date
0
Altmetric
Review Article

Neonatal Fc receptor (FcRn): a novel target for therapeutic antibodies and antibody engineering

, , &
Pages 269-278 | Received 04 Aug 2013, Accepted 10 Dec 2013, Published online: 09 Jan 2014

References

  • Boswell CA, Tesar DB, Mukhyala K, et al. Effects of charge on antibody tissue distribution and pharmacokinetics. Bioconjugate Chem 2010;21:2153–63
  • Background: monoclonal antibody therapeutics. Available from: http://www.landesbioscience.com/journals/mabs/about/#background [modified in text and last accessed 18 Dec 2013]
  • Reichert JM. Marketed therapeutic antibodies compendium. MAbs 2012;4:413–15
  • Roopenian DC, Akilesh S. FcRn: the neonatal Fc receptor comes of age. Nat Rev Immunol 2007;7:715–25
  • Vincent KJ, Zurini M. Current strategies in antibody engineering: Fc engineering and pH-dependent antigen binding, bispecific antibodies and antibody drug conjugates. Biotechnol J 2012;7:1444–50
  • Lobo ED, Hansen RJ, Balthasar JP. Antibody pharmacokinetics and pharmacodynamics. J Pharm Sci. 2004;93:2645–68
  • Spiegelberg HL. Biological activities of Igs of different classes and subclasses. Adv Immunol 1974;19:259–94
  • Wang W, Lu P, Fang Y, et al. Monoclonal antibodies with identical Fc sequences can bind to FcRndifferentially with pharmacokinetic consequences. Drug Metab Dispos 2011;39:1469–77
  • Grey HM, Kunkel HG. H Chain subgroups of myeloma proteins and normal 7S γ-globulin. J Exp Med 1964;120:253–66
  • Burton DR, Gregory L, Jefferis R. Aspects of the molecular structure of the IgG subclasses. Monogr Allergy 1986;19:7–35
  • Pumphrey R. Computer models of the human immunoglobulins shape and segmental flexibility. Immunol Today 1986;7:174–8
  • Shakib F, Stanworth DR. Human IgG subclasses in health and disease (a review). Part I. Ric Clin Lab 1980;10:463–79
  • Meulenbroek AJ. Human IgG subclasses: useful diagnostic markers for immunocompetence. Amsterdam, Netherlands: Sanquin; 2008
  • Nimmerjahn F, Ravetch JV. Fcγ receptors: old friends and new family members. Immunity 2006;24:19–28
  • Shields RL, Namenuk AK, Hong K, et al. High resolution mapping of the binding site on human IgG1 for FcγRI, FcγRII, FcγRIII, and FcRn and design of IgG1 variants with improved binding to the FcγR. J Biol Chem 2001;276:6591–604
  • Vidarsson G, Stemerding AM, Stapleton NM, et al. FcRn: an IgG receptor on phagocytes with a novel role in phagocytosis. Blood 2006;108:3573–9
  • Simister NE, Mostov KE. An Fc receptor structurally related to MHC class I antigens. Nature 1989;337:184–7
  • Mezo AR, Sridhar V, Badger J, et al. X-ray crystal structures of monomeric and dimeric peptide inhibitors in complex with the human neonatal Fc receptor, FcRn. J Biol Chem 2010;258:27694–701
  • Bai Y, Ye L, Tesar DB, et al. Intracellular neutralization of viral infection in polarized epithelial cells by neonatal Fc receptor (FcRn)-mediated IgG transport. Proc Natl Acad Sci USA 2011;108:18406–11
  • Rodewald R, Kraehenbuhl J-P. Receptor-mediated transport of IgG. J Cell Biol 1984;99:159–64
  • Yoshida M, Claypool SM, Wagner JS, et al. Human neonatal Fc receptor mediates transport of IgG into luminal secretions for delivery of antigens to mucosal dendritic cells. Immunity 2004;20:769–83
  • Bitonti AJ, Dumont JA. Pulmonary administration of therapeutic proteins using an immunoglobulin transport pathway. Adv Drug Deliv Rev 2006;58:1106–18
  • Kuo TT, Baker K, Yoshida M, et al. Neonatal Fc receptor: from immunity to therapeutics. J Clin Immunol 2010;30:777–89
  • Vallee S, Rakhe S, Reidy T, et al. Pulmonary administration of interferon Beta-1a-fc fusion protein in non-human primates using an immunoglobulin transport pathway. J Interferon Cytokine Res 2012;32:178–84
  • Raghavan M, Gastinel LN, Bjorkman PJ. The class I major histocompatibility complex related Fc receptor shows pH-dependent stability differences correlating with immunoglobulin binding and release. Biochemistry 1993;32:8654–60
  • Yeung YA, Leabman MK, Marvin JS, et al. Engineering human IgG1 affinity to human neonatal Fc receptor: impact of affinity improvement on pharmacokinetics in primates. J Immunol 2009;182:7663–71
  • Martin WL, West AP Jr, Gan L, Bjorkman PJ. Crystal structure at 2.8 Å of an FcRn/heterodimeric Fc complex: mechanism of pH-dependent binding. Mol Cell 2001;7:867–77
  • Bumbaca D, Boswell CA, Fielder PJ, Khawli LA. Physiochemical and biochemical factors influencing the pharmacokinetics of antibody therapeutics. AAPS J 2012;14:554–8
  • Zalevsky J, Chamberlain AK, Horton HM, et al. Enhanced antibody half-life improves in vivo activity. Nat Biotechnol 2010;28:157–9
  • Xie XM, Richard G, Hall JC. Antibody fragment engineering and applications in diagnosis and therapeutics. In: Meulenberg EP, ed. Antibodies applications and new developments. Illinois: Bentham Science Publishers; 2012:225–79
  • Ying T, Chen W, Gong R, et al. Soluble monomeric IgG1 Fc. J Biol Chem 2012;287:19399–408
  • Gong R, Wang Y, Feng Y, et al. Shortened engineered human antibody CH2 domains increased stability and binding to the human neonatal Fc receptor. J Biol Chem 2011;286:27288–93
  • Gong R, Vu BK, Feng Y, et al. Engineered human antibody constant domains with increased stability. J Biol Chem 2009;284:14203–10
  • Shimizu A, Honzawa M, Ito S, et al. H NMR studies of the Fc region of human IgG1 and IgG3 immunoglobulins: assignment of histidine resonances in the CH3 domain and identification of IgG3 protein carrying G3m (st) allotypes. Mol Immunol 1983;20:141–8
  • Stapleton NM, Andersen JT, Stemerding AM, et al. Competition for FcRn-mediated transport gives rise to short half-life of human IgG3 and offers therapeutic potential. Nat Commun 2011;2:599. doi:https://doi.org/10.1038/ncomms1608
  • Cervenak J, Bender B, Schneider Z, et al. Neonatal FcR overexpression boosts humoral immune response in transgenic mice. J Immunol 2011;186:959–68
  • Bender B, Bodrogi L, Mayer B, et al. Position independent and copy-number-related expression of the bovine neonatal Fc receptor α-chain in transgenic mice carrying a 102 kb BAC genomic fragment. Transgenic Res 2007;16:613–27
  • Catunda Lemos AP, Cervenak J, Bender B, et al. Characterization of the rabbit neonatal Fc receptor (FcRn) and analyzing the immunophenotype of the transgenic rabbits that overexpresses FcRn. PLoS One 2012;7:1–14
  • Kacskovics I, Cervenak J, Erdei A, et al. Recent advances using FcRn over-expression in transgenic animals to overcome impediments of standard antibody technologies to improve the generation of specific antibodies. MAbs 2012;3:431–9
  • Sesarman A, Vidarsson G, Sitaru C. The neonatal Fc receptor as therapeutic target in IgG-mediated autoimmune diseases. Cell Mol Life Sci 2010;67:2533–50
  • Getman KE, Balthasar JP. Pharmacokinetic effects of 4C9, an anti-FcRn antibody, in rats: implications for the use of FcRn inhibitors for the treatment of humoral autoimmune and alloimmune conditions. J Pharm Sci 2005;94:718–29
  • Liu L, Garcia AM, Santoro H, et al. Amelioration of experimental autoimmune myasthenia gravis in rats by neonatal FcR blockade. J Immunol 2007;178:5390–8
  • Mezo AR, McDonnell KA, Hehir CA, et al. Reduction of IgG in nonhuman primates by a peptide antagonist of the neonatal Fc receptor FcRn. Proc Natl Acad Sci USA 2008;105:2337–42
  • Wang Z, Fraley C, Mezo AR. Discovery and structure–activity relationships of small molecules that block the human immunoglobulin G–human neonatal Fc receptor (hIgG–hFcRn) protein–protein interaction. Bioorg Med Chem Lett 2013;23:1253–6
  • Kuo TT, Aveson VG. Neonatal Fc receptor and IgG-based therapeutics. MAbs 2011;3:422–30
  • Végh A, Cervenak J, Jankovics I, Kacskovics I. FcRn over-expression in mice results in potent humoral response against weakly immunogenic antigen. MAbs 2011;3:173–80
  • Végh A, Farkas A, Kövesdi D, et al. FcRn over-expression in transgenic mice results in augmented APC activity and robust immune response with increased diversity of induced antibodies. PLoS One 2012;7:1–11
  • Dall'Acqua WF, Kiener PA, Wu H. Properties of human IgG1s engineered for enhanced binding to the neonatal Fc receptor (FcRn). J Biol Chem 2006;281:23514–24
  • Hinton PR, Johlfs MG, Xiong JM, et al. Engineered human IgG antibodies with longer serum half-lives in primates. J Biol Chem 2004;279:6213–6
  • Hinton PR, Xiong JM, Johlfs MG, et al. An engineered human IgG1 antibody with longer serum half-Life. J Immunol 2006;176:346–56
  • Petkova SB, Akilesh S, Sproule TJ, et al. Enhanced half-life of genetically engineered human IgG1 antibodies in a humanized FcRn mouse model: potential application in humorally mediated autoimmune disease. Int Immunol 2006;18:1759–69

Reprints and Corporate Permissions

Please note: Selecting permissions does not provide access to the full text of the article, please see our help page How do I view content?

To request a reprint or corporate permissions for this article, please click on the relevant link below:

Academic Permissions

Please note: Selecting permissions does not provide access to the full text of the article, please see our help page How do I view content?

Obtain permissions instantly via Rightslink by clicking on the button below:

If you are unable to obtain permissions via Rightslink, please complete and submit this Permissions form. For more information, please visit our Permissions help page.