title: Targeting FcRn for therapy: from live cell imaging to in vivo studies in mice.
abstract: The role of FcRn in regulating antibody levels and transport in the body is well documented. The use of fluorescence microscopy to investigate the subcellular trafficking behavior of FcRn and its IgG ligand has led to insight into the function of this receptor, including the identification of new intracellular pathways. The inhibition of FcRn using engineered antibodies that bind to this receptor with increased affinity through their Fc region can be exploited to treat antibody mediated autoimmunity. The efficacy of this approach in mouse models of arthritis and multiple sclerosis has been demonstrated. Finally, the cross-species difference between mouse and man for FcRn-IgG interactions needs to be considered when engineering antibodies for improved activities in FcRn-mediated functions.
authors.affiliation: Department of Immunology, University of Texas Southwestern Medical Center, 5323 Harry Hines Boulevard, Dallas, TX 75390, USA. Electronic address: sally.ward@utsouthwestern.edu.
authors.forename: E Sally
authors.initials: ES
authors.lastname: Ward
authors.affiliation: Department of Immunology, University of Texas Southwestern Medical Center, 5323 Harry Hines Boulevard, Dallas, TX 75390, USA; Biomedical Engineering Graduate Program, University of Texas Southwestern Medical Center, 5323 Harry Hines Boulevard, Dallas TX 75390, USA. Electronic address: ramraj.velmurugan@utsouthwestern.edu.
authors.forename: Ramraj
authors.initials: R
authors.lastname: Velmurugan
authors.affiliation: Department of Immunology, University of Texas Southwestern Medical Center, 5323 Harry Hines Boulevard, Dallas, TX 75390, USA; Department of Electrical Engineering, University of Texas at Dallas, Richardson, TX 75080, USA. Electronic address: raimund.ober@utsouthwestern.edu.
authors.forename: Raimund J
authors.initials: RJ
authors.lastname: Ober
mesh_terms: D000818:Animals; D000906:Antibodies / Q000235:genetics / Q000276:immunology / Q000494:pharmacology*; D001168:Arthritis / Q000235:genetics / Q000276:immunology / Q000473:pathology / Q000628:therapy*; D004195:Disease Models, Animal; D015870:Gene Expression; D006801:Humans; D007116:Immunization, Passive; D007074:Immunoglobulin G / Q000235:genetics / Q000276:immunology*; D051379:Mice; D008822:Mice, Transgenic; D057054:Molecular Imaging; D009103:Multiple Sclerosis / Q000235:genetics / Q000276:immunology / Q000473:pathology / Q000628:therapy*; D011485:Protein Binding; D015202:Protein Engineering; D011961:Receptors, Fc / Q000235:genetics / Q000276:immunology*
chemical_list: D000906:Antibodies; D007074:Immunoglobulin G; D011961:Receptors, Fc
keywords: Antibody engineering; Antibody pharmacokinetics; Autoimmunity; FcRn; Immunoglobulin G; Live-imaging microscopy