6,433
Views
51
CrossRef citations to date
0
Altmetric
Report

Changes in complementarity-determining regions significantly alter IgG binding to the neonatal Fc receptor (FcRn) and pharmacokinetics

, , , , , , & show all
Pages 81-94 | Received 16 Jan 2015, Accepted 02 Oct 2017, Published online: 03 Nov 2017

References

  • Wang W, Wang EQ, Balthasar JP. Monoclonal antibody pharmacokinetics and pharmacodynamics. Clin Pharmacol Ther. 2008;84:548–58. doi:10.1038/clpt.2008.170. PMID:18784655.
  • Acqua WFD, Woods RM, Ward ES, Palaszynski SR, Patel NK, Brewah YA, Wu H, Kiener PA, Langermann S. Increasing the Affinity of a Human IgG1 for the Neonatal Fc Receptor: Biological Consequences. The Journal of Immunology. 2002;169:5171–80. doi:10.4049/jimmunol.169.9.5171. PMID:12391234.
  • Borrok MJ, Wu Y, Beyaz N, Yu X-Q, Oganesyan V, Dall'Acqua WF, Tsui P. pH-dependent Binding Engineering Reveals an FcRn Affinity Threshold That Governs IgG Recycling. Journal of Biological Chemistry. 2015;290:4282–90. doi:10.1074/jbc.M114.603712. PMID:25538249.
  • 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. doi:10.1074/jbc.M604292200. PMID:16793771.
  • Datta-Mannan A, Thangaraju A, Leung D, Tang Y, Witcher DR, Lu J, Wroblewski VJ. Balancing charge in the complementarity-determining regions of humanized mAbs without affecting pI reduces non-specific binding and improves the pharmacokinetics. mAbs. 2015;7:483–93. doi:10.1080/19420862.2015.1016696. PMID:25695748.
  • Finch DK, Sleeman MA, Moisan J, Ferraro F, Botterell S, Campbell J, Cochrane D, Cruwys S, England E, Lane S, et al. Whole-molecule antibody engineering: generation of a high-affinity anti-IL-6 antibody with extended pharmacokinetics. J Mol Biol. 2011;411:791–807. doi:10.1016/j.jmb.2011.06.031. PMID:21723291.
  • Firan M, Bawdon R, Radu C, Ober RJ, Eaken D, Antohe F, Ghetie V, Ward ES. The MHC class I-related receptor, FcRn, plays an essential role in the maternofetal transfer of gamma-globulin in humans. Int Immunol. 2001;13:993–1002. doi:10.1093/intimm/13.8.993. PMID:11470769.
  • Ghetie V, Popov S, Borvak J, Radu C, Matesoi D, Medesan C, Ober RJ, Ward ES. Increasing the serum persistence of an IgG fragment by random mutagenesis. Nat Biotech. 1997;15:637–40. doi:10.1038/nbt0797-637.
  • Ghetie V, Ward ES. Multiple roles for the major histocompatibility complex class I- related receptor FcRn. Annu Rev Immunol. 2000;18:739–66. doi:10.1146/annurev.immunol.18.1.739. PMID:10837074.
  • Kim JK, Tsen MF, Ghetie V, Ward ES. Localization of the site of the murine IgG1 molecule that is involved in binding to the murine intestinal Fc receptor. Eur J Immunol. 1994;24:2429–34. doi:10.1002/eji.1830241025. PMID:7925571.
  • Suzuki T, Ishii-Watabe A, Tada M, Kobayashi T, Kanayasu-Toyoda T, Kawanishi T, Yamaguchi T. Importance of neonatal FcR in regulating the serum half-life of therapeutic proteins containing the Fc domain of human IgG1: a comparative study of the affinity of monoclonal antibodies and Fc-fusion proteins to human neonatal FcR. J Immunol. 2010;184:1968–76. doi:10.4049/jimmunol.0903296. PMID:20083659.
  • Ward ES, Zhou J, Ghetie V, Ober RJ. Evidence to support the cellular mechanism involved in serum IgG homeostasis in humans. Int Immunol. 2003;15:187–95. doi:10.1093/intimm/dxg018. PMID:12578848.
  • Yeung YA, Wu X, Reyes AE, 2nd, Vernes JM, Lien S, Lowe J, Maia M, Forrest WF, Meng YG, Damico LA, et al. A therapeutic anti-VEGF antibody with increased potency independent of pharmacokinetic half-life. Cancer Res. 2010;70:3269–77. doi:10.1158/0008-5472.CAN-09-4580. PMID:20354184.
  • Zalevsky J, Chamberlain AK, Horton HM, Karki S, Leung IW, Sproule TJ, Lazar GA, Roopenian DC, Desjarlais JR. Enhanced antibody half-life improves in vivo activity. Nat Biotechnol. 2010;28:157–9. doi:10.1038/nbt.1601. PMID:20081867.
  • Zhou J, Johnson JE, Ghetie V, Ober RJ, Ward ES. Generation of mutated variants of the human form of the MHC class I-related receptor, FcRn, with increased affinity for mouse immunoglobulin G. J Mol Biol. 2003;332:901–13. doi:10.1016/S0022-2836(03)00952-5. PMID:12972260.
  • Jensen PF, Schoch A, Larraillet V, Hilger M, Schlothauer T, Emrich T, Rand KD. A Two-pronged Binding Mechanism of IgG to the Neonatal Fc Receptor Controls Complex Stability and IgG Serum Half-life. Mol Cell Proteomics. 2017;16:451–6. doi:10.1074/mcp.M116.064675.
  • Schlothauer T, Rueger P, Stracke JO, Hertenberger H, Fingas F, Kling L, Emrich T, Drabner G, Seeber S, Auer J, et al. Analytical FcRn affinity chromatography for functional characterization of monoclonal antibodies. mAbs. 2013;5:576–86. doi:10.4161/mabs.24981. PMID:23765230.
  • Schoch A, Kettenberger H, Mundigl O, Winter G, Engert J, Heinrich J, Emrich T. Charge-mediated influence of the antibody variable domain on FcRn-dependent pharmacokinetics. Proc Natl Acad Sci U S A. 2015;112:5997–6002. doi:10.1073/pnas.1408766112.
  • Wang W, Lu P, Fang Y, Hamuro L, Pittman T, Carr B, Hochman J, Prueksaritanont T. Monoclonal antibodies with identical Fc sequences can bind to FcRn differentially with pharmacokinetic consequences. Drug Metab Dispos. 2011;39:1469–77. doi:10.1124/dmd.111.039453. PMID:21610128.
  • Lobo ED, Hansen RJ, Balthasar JP. Antibody pharmacokinetics and pharmacodynamics. J Pharm Sci. 2004;93:2645–68. doi:10.1002/jps.20178. PMID:15389672.
  • Burmeister WP, Huber AH, Bjorkman PJ. Crystal structure of the complex of rat neonatal Fc receptor with Fc. Nature 1994;372:379–83. doi:10.1038/372379a0. PMID:7969498.
  • Martin WL, West AP, Jr., Gan L, Bjorkman PJ. Crystal structure at 2.8 A of an FcRn/heterodimeric Fc complex: mechanism of pH-dependent binding. Mol Cell. 2001;7:867–77. doi:10.1016/S1097-2765(01)00230-1. PMID:11336709.
  • Burmeister WP, Gastinel LN, Simister NE, Blum ML, Bjorkman PJ. Crystal structure at 2.2 A resolution of the MHC-related neonatal Fc receptor. Nature. 1994;372:336–43. doi:10.1038/372336a0. PMID:7969491.
  • West AP, Jr., Bjorkman PJ. Crystal structure and immunoglobulin G binding properties of the human major histocompatibility complex-related Fc receptor. Biochemistry. 2000;39:9698–708. doi:10.1021/bi000749m. PMID:10933786.
  • Igawa T, Tsunoda H, Tachibana T, Maeda A, Mimoto F, Moriyama C, Nanami M, Sekimori Y, Nabuchi Y, Aso Y, et al. Reduced elimination of IgG antibodies by engineering the variable region. Protein Eng Des Sel. 2010;23:385–92. doi:10.1093/protein/gzq009. PMID:20159773.
  • Li B, Tesar D, Boswell CA, Cahaya HS, Wong A, Zhang J, Meng YG, Eigenbrot C, Pantua H, Diao J, et al. Framework selection can influence pharmacokinetics of a humanized therapeutic antibody through differences in molecule charge. mAbs. 2014;6:1255–64. doi:10.4161/mabs.29809. PMID:25517310.
  • Myszka DG. Improving biosensor analysis. J Mol Recognit 1999;12:279–84. doi:10.1002/(SICI)1099-1352(199909/10)12:5%3c279::AID-JMR473%3e3.0.CO;2-3. PMID:10556875.
  • Rich RL, Myszka DG. Survey of the year. 2007 commercial optical biosensor literature. Journal of Molecular Recognition. 2008;21:355–400. doi:10.1002/jmr.928. PMID:18951413.
  • Avery LB, Wang M, Kavosi MS, Joyce A, Kurz JC, Fan Y-Y, Dowty ME, Zhang M, Zhang Y, Cheng A, et al. Utility of a human FcRn transgenic mouse model in drug discovery for early assessment and prediction of human pharmacokinetics of monoclonal antibodies. mAbs. 2016;8:1064–78. doi:10.1080/19420862.2016.1193660. PMID:27232760.
  • Gurbaxani B, Dela Cruz LL, Chintalacharuvu K, Morrison SL. Analysis of a family of antibodies with different half-lives in mice fails to find a correlation between affinity for FcRn and serum half-life. Mol Immunol. 2006;43:1462–73. doi:10.1016/j.molimm.2005.07.032. PMID:16139891.
  • Thorn M, Piche-Nicholas N, Stedman D, Davenport SW, Zhang N, Collinge M, Bowman CJ. Embryo-Fetal Transfer of Bevacizumab (Avastin) in the Rat Over the Course of Gestation and the Impact of Neonatal Fc Receptor (FcRn) Binding. Birth Defects Research Part B: Developmental and Reproductive Toxicology. 2012;95:363–75. doi:10.1002/bdrb.21026.
  • Abdiche YN, Yeung YA, Chaparro-Riggers J, Barman I, Strop P, Chin SM, Pham A, Bolton G, McDonough D, Lindquist K, et al. The neonatal Fc receptor (FcRn) binds independently to both sites of the IgG homodimer with identical affinity. mAbs. 2015;7:331–43. doi:10.1080/19420862.2015.1008353. PMID:25658443.
  • Huber AH, Kelley RF, Gastinel LN, Bjorkman PJ. Crystallization and stoichiometry of binding of a complex between a rat intestinal Fc receptor and Fc. J Mol Biol. 1993;230:1077–83. doi:10.1006/jmbi.1993.1220. PMID:8478919.
  • Kim JK, Firan M, Radu CG, Kim CH, Ghetie V, Ward ES. Mapping the site on human IgG for binding of the MHC class I-related receptor, FcRn. Eur J Immunol. 1999;29:2819–25. doi:10.1002/(SICI)1521-4141(199909)29:09%3c2819::AID-IMMU2819%3e3.0.CO;2-6. PMID:10508256.
  • Bongini L, Fanelli D, Piazza F, De Los Rios P, Sandin S, Skoglund U. Freezing immunoglobulins to see them move. Proc Natl Acad Sci U S A. 2004;101:6466–71. doi:10.1073/pnas.0400119101. PMID:15082830.
  • Bongini L, Fanelli D, Piazza F, De Los Rios P, Sandin S, Skoglund U. Dynamics of antibodies from cryo-electron tomography. Biophys Chem. 2005;115:235–40. doi:10.1016/j.bpc.2004.12.037. PMID:15752611.
  • Tian X, Vestergaard B, Thorolfsson M, Yang Z, Rasmussen HB, Langkilde AE. In-depth analysis of subclass-specific conformational preferences of IgG antibodies. IUCrJ. 2015;2:9–18. doi:10.1107/S205225251402209X. PMID:25610623.
  • Bumbaca D, Wong A, Drake E, Reyes AE, 2nd, Lin BC, Stephan JP, Desnoyers L, Shen BQ, Dennis MS. Highly specific off-target binding identified and eliminated during the humanization of an antibody against FGF receptor 4. MAbs. 2011;3:376–86. doi:10.4161/mabs.3.4.15786. PMID:21540647.
  • Wu H, Pfarr DS, Johnson S, Brewah YA, Woods RM, Patel NK, White WI, Young JF, Kiener PA. Development of motavizumab, an ultra-potent antibody for the prevention of respiratory syncytial virus infection in the upper and lower respiratory tract. J Mol Biol. 2007;368:652–65. doi:10.1016/j.jmb.2007.02.024. PMID:17362988.
  • Malek A, Sager R, Kuhn P, Nicolaides KH, Schneider H. Evolution of maternofetal transport of immunoglobulins during human pregnancy. Am J Reprod Immunol. 1996;36:248–55. doi:10.1111/j.1600-0897.1996.tb00172.x. PMID:8955500.
  • Bloom JW, Madanat MS, Marriott D, Wong T, Chan SY. Intrachain disulfide bond in the core hinge region of human IgG4. Protein Sci. 1997;6:407–15. doi:10.1002/pro.5560060217. PMID:9041643.
  • Rayner LE, Hui GK, Gor J, Heenan RK, Dalby PA, Perkins SJ. The Fab Conformations in the Solution Structure of Human Immunoglobulin G4 (IgG4) Restrict Access to Its Fc Region: IMPLICATIONS FOR FUNCTIONAL ACTIVITY. J Biol Chem. 2014;289:20740–56. doi:10.1074/jbc.M114.572404. PMID:24876381.
  • Diebolder CA, Beurskens FJ, de Jong RN, Koning RI, Strumane K, Lindorfer MA, Voorhorst M, Ugurlar D, Rosati S, Heck AJR, et al. Complement Is Activated by IgG Hexamers Assembled at the Cell Surface. Science. 2014;343:1260–3. doi:10.1126/science.1248943. PMID:24626930.
  • Cook EM, Lindorfer MA, van der Horst H, Oostindie S, Beurskens FJ, Schuurman J, Zent CS, Burack R, Parren PWHI, Taylor RP. Antibodies That Efficiently Form Hexamers upon Antigen Binding Can Induce Complement-Dependent Cytotoxicity under Complement-Limiting Conditions. J Immunol. 2016;197:1762–75. doi:10.4049/jimmunol.1600648. PMID:27474078.
  • Hadzhieva M, Pashov AD, Kaveri S, Lacroix-Desmazes S, Mouquet H, Dimitrov JD. Impact of Antigen Density on the Binding Mechanism of IgG Antibodies. Sci Rep. 2017;7:3767. doi:10.1038/s41598-017-03942-z. PMID:28630473.
  • Piekarska B, Drozd A, Konieczny L, Król M, Jurkowski W, Roterman I, Spólnik P, Stopa B, Rybarska J. The Indirect Generation of Long-distance Structural Changes in Antibodies upon their Binding to Antigen. Chem Biol Drug Des. 2006;68:276–83. doi:10.1111/j.1747-0285.2006.00448.x.
  • Jensen PF, Larraillet V, Schlothauer T, Kettenberger H, Hilger M, Rand KD. Investigating the Interaction between the Neonatal Fc Receptor and Monoclonal Antibody Variants by Hydrogen/Deuterium Exchange Mass Spectrometry. Mol Cell Proteomics. 2015;14:148–61. doi:10.1074/mcp.M114.042044.
  • Gurbaxani B, Dostalek M, Gardner I. Are endosomal trafficking parameters better targets for improving mAb pharmacokinetics than FcRn binding affinity? Mol Immunol. 2013;56:660–74. doi:10.1016/j.molimm.2013.05.008. PMID:23917469.
  • Unverdorben F, Richter F, Hutt M, Seifert O, Malinge P, Fischer N, Kontermann RE. Pharmacokinetic properties of IgG and various Fc fusion proteins in mice. mAbs. 2016;8:120–8. doi:10.1080/19420862.2015.1113360. PMID:26514880.
  • Joyce AP, Wang M, Lawrence-Henderson R, Filliettaz C, Leung SS, Xu X, O'Hara DM. One Mouse, One Pharmacokinetic Profile: Quantitative Whole Blood Serial Sampling for Biotherapeutics. Pharm Res. 2014;31:1823–33. doi:10.1007/s11095-013-1286-y. PMID:24464271.