Fc engineering: serum half-life modulation through FcRn binding.
Controlling the half-life of pharmaceuticals through Fc engineering is a desirable approach to achieve optimal exposure and targeting. The long serum residence time of gamma immunoglobulins is attributed to the Fc binding to the neonatal Fc receptor (FcRn). The residues in the Fc region that interact with FcRn have been mapped and individual mutations of these residues have demonstrated reduced affinity to FcRn and faster blood clearance. Here, we describe site-specific mutagenesis of Fc residues in a scFv-Fc fusion protein, as well as the mammalian production, purification, characterization, and the in vivo pharmacokinetics of these antibody fragments.
Department of Molecular and Medical Pharmacology, Crump Institute for Molecular Imaging, David Geffen School of Medicine at UCLA, Los Angeles, CA, USA. tolafsen@mednet.ucal.edu
Tove
T
Olafsen
D000818:Animals; D002846:Chromatography, Affinity; D002855:Chromatography, Thin Layer; D006207:Half-Life; D015395:Histocompatibility Antigens Class I / Q000235:genetics / Q000302:isolation & purification / Q000378:metabolism*; D006801:Humans; D007457:Iodine Radioisotopes; D051379:Mice; D016297:Mutagenesis, Site-Directed; D011485:Protein Binding; D015202:Protein Engineering / Q000379:methods*; D011961:Receptors, Fc / Q000235:genetics / Q000302:isolation & purification / Q000378:metabolism*; D011993:Recombinant Fusion Proteins / Q000302:isolation & purification / Q000493:pharmacokinetics; D044967:Serum / Q000378:metabolism*
D015395:Histocompatibility Antigens Class I; D007457:Iodine Radioisotopes; D011961:Receptors, Fc; D011993:Recombinant Fusion Proteins; C100688:Fc receptor, neonatal