1,775
Views
0
CrossRef citations to date
0
Altmetric
Report

Insight into the avidity–affinity relationship of the bivalent, pH-dependent interaction between IgG and FcRn

, , & ORCID Icon
Article: 2361585 | Received 01 Oct 2023, Accepted 24 May 2024, Published online: 07 Jun 2024

References

  • Nelson AL, Dhimolea E, Reichert JM. Development trends for human monoclonal antibody therapeutics. Nat Rev Drug Discov. 2010;9(10):767–17. doi:10.1038/nrd3229. PMID: 20811384.
  • Kaplon H, Chenoweth A, Crescioli S, Reichert JM. Antibodies to watch in 2022. Mabs-austin. 2022;14(1):2014296. doi:10.1080/19420862.2021.2014296. PMID: 35030985.
  • Dostalek M, Prueksaritanont T, Kelley RF. Pharmacokinetic de-risking tools for selection of monoclonal antibody lead candidates. Mabs-austin. 2017;9(5):756–66. doi:10.1080/19420862.2017.1323160. PMID: 28463063.
  • Muller T, Tasser C, Tesar M, Fucek I, Schniegler-Mattox U, Koch J, Ellwanger K. Selection of bispecific antibodies with optimal developability using FcRn‑Ph‑HPLC as an optimized FcRn affinity chromatography method. Mabs-austin. 2023;15(1):2245519. doi:10.1080/19420862.2023.2245519. PMID: 37599441.
  • Fernandez-Quintero ML, Ljungars A, Waibl F, Greiff V, Andersen JT, Gjolberg TT, Jenkins TP, Voldborg BG, Grav LM, Kumar S. et al. Assessing developability early in the discovery process for novel biologics. Mabs-austin. 2023;15(1):2171248. doi:10.1080/19420862.2023.2171248. PMID: 36823021.
  • Baldwin WM 3rd, Valujskikh A, Fairchild RL. The neonatal Fc receptor: key to homeostasic control of IgG and IgG-related biopharmaceuticals. Am J Transplant. 2019;19(7):1881–87. doi:10.1111/ajt.15366. PMID: 30903736.
  • Ward ES, Ober RJ. Targeting FcRn to generate antibody-based therapeutics. Trends Pharmacol Sci. 2018;39(10):892–904. doi:10.1016/j.tips.2018.07.007. PMID: 30143244.
  • Pyzik M, Sand KMK, Hubbard JJ, Andersen JT, Sandlie I, Blumberg RS. The neonatal Fc Receptor (FcRn): a misnomer? Front Immunol. 2019;10:1540. doi:10.3389/fimmu.2019.01540. PMID: 31354709.
  • D’Hooghe L, Chalmers AD, Heywood S, Whitley P, Johannes L. Cell surface dynamics and cellular distribution of endogenous FcRn. PLOS ONE. 2017;12(8):e0182695. doi:10.1371/journal.pone.0182695. PMID: 28817705.
  • Pyzik M, Kozicky LK, Gandhi AK, Blumberg RS. The therapeutic age of the neonatal Fc receptor. Nat Rev Immunol. 2023;23(7):415–32. doi:10.1038/s41577-022-00821-1. PMID: 36726033.
  • Oostindie SC, Lazar GA, Schuurman J, Parren P. Avidity in antibody effector functions and biotherapeutic drug design. Nat Rev Drug Discov. 2022;21(10):715–35. doi:10.1038/s41573-022-00501-8. PMID: 35790857.
  • Karush F. Multivalent binding and functional affinity. Contemp Top Mol Immunol. 1976;5:217–28. doi:10.1007/978-1-4684-8142-6_8. PMID: 63353.
  • Fan YY, Farrokhi V, Caiazzo T, Wang M, O’Hara DM, Neubert H. Human FcRn tissue expression profile and half-life in PBMCs. Biomolecules. 2019;9(8):373. doi:10.3390/biom9080373. PMID: 31443181.
  • Roopenian DC, Akilesh S. FcRn: the neonatal Fc receptor comes of age. Nat Rev Immunol. 2007;7(9):715–25. doi:10.1038/nri2155. PMID: 17703228.
  • Latvala S, Jacobsen B, Otteneder MB, Herrmann A, Kronenberg S. Distribution of FcRn across species and tissues. J Histochem Cytochem. 2017;65(6):321–33. doi:10.1369/0022155417705095. PMID: 28402755.
  • Rudnik-Jansen I, Howard KA. FcRn expression in cancer: mechanistic basis and therapeutic opportunities. J Controlled Release. 2021;337:248–57. doi:10.1016/j.jconrel.2021.07.007.
  • Swiercz R, Mo M, Khare P, Schneider Z, Ober RJ, Ward ES. Loss of expression of the recycling receptor, FcRn, promotes tumor cell growth by increasing albumin consumption. Oncotarget. 2017;8(2):3528–41. doi:10.18632/oncotarget.13869. PMID: 27974681.
  • Pyzik M, Rath T, Lencer WI, Baker K, Blumberg RS. FcRn: the architect behind the immune and nonimmune functions of IgG and albumin. J Immunol. 2015;194(10):4595–603. doi:10.4049/jimmunol.1403014. PMID: 25934922.
  • Ward ES, Devanaboyina SC, Ober RJ. Targeting FcRn for the modulation of antibody dynamics. Mol Immunol. 2015;67(2):131–41. doi:10.1016/j.molimm.2015.02.007. PMID: 25766596.
  • Ward ES, Velmurugan R, Ober RJ. Targeting FcRn for therapy: from live cell imaging to in vivo studies in mice. Immunol Lett. 2014;160(2):158–62. doi:10.1016/j.imlet.2014.02.008. PMID: 24572175.
  • Dickinson BL, Badizadegan K, Wu Z, Ahouse JC, Zhu X, Simister NE, Blumberg RS, Lencer WI. Bidirectional FcRn-dependent IgG transport in a polarized human intestinal epithelial cell line. J Clin Invest. 1999;104(7):903–11. doi:10.1172/JCI6968. PMID: 10510331.
  • Spiekermann GM, Finn PW, Ward ES, Dumont J, Dickinson BL, Blumberg RS, Lencer WI. Receptor-mediated immunoglobulin G transport across mucosal barriers in adult life: functional expression of FcRn in the mammalian lung. J Exp Med. 2002;196(3):303–10. doi:10.1084/jem.20020400. PMID: 12163559.
  • Foss S, Grevys A, Sand KMK, Bern M, Blundell P, Michaelsen TE, Pleass RJ, Sandlie I, Andersen JT. Enhanced FcRn-dependent transepithelial delivery of IgG by Fc-engineering and polymerization. J Control Release. 2016;223:42–52. doi:10.1016/j.jconrel.2015.12.033. PMID: 26718855.
  • Hubbard JJ, Pyzik M, Rath T, Kozicky LK, Sand KMK, Gandhi AK, Grevys A, Foss S, Menzies SC, Glickman JN. et al. FcRn is a CD32a coreceptor that determines susceptibility to IgG immune complex–driven autoimmunity. J Exp Med. 2020;217(10). doi:10.1084/jem.20200359. PMID: 32658257.
  • Baker K, Qiao SW, Kuo TT, Aveson VG, Platzer B, Andersen JT, Sandlie I, Chen Z, de Haar C, Lencer WI. et al. Neonatal Fc receptor for IgG (FcRn) regulates cross-presentation of IgG immune complexes by CD8−CD11b+dendritic cells. Proc Natl Acad Sci USA. 2011;108(24):9927–32. doi:10.1073/pnas.1019037108. PMID: 21628593.
  • Qiao SW, Kobayashi K, Johansen FE, Sollid LM, Andersen JT, Milford E, Roopenian DC, Lencer WI, Blumberg RS. Dependence of antibody-mediated presentation of antigen on FcRn. Proc Natl Acad Sci USA. 2008;105(27):9337–42. doi:10.1073/pnas.0801717105. PMID: 18599440.
  • Brambell FWR. The PASSIVE IMMUNITY of the YOUNG MAMMAL. Biol Rev. 1958;33(4):488–531. doi:10.1111/j.1469-185X.1958.tb01412.x.
  • Burmeister Ahh WP, Bjorkman PJ. Crystal structure of the complex of rat neonatal Fc receptor with Fc. Nature. 1994; 372. doi:10.1038/372379a0.
  • Burmeister Lng WP, Simister NE, Blum ML, Bjorkman PJ. Crystal structure at 2.2 Å resolution of the MHC-related neonatal Fc receptor. Nature. 1994; doi:10.1038/372336a0.
  • Simister NE, Mostov KE. An Fc receptor structurally related to MHC class I antigens. Nature. 1989;337(6203):184–87. doi:10.1038/337184a0.
  • Malini Raghavan VRB, Morrison SL, Bjorkman PJ. Analysis of the pH dependence of the neonatal Fc receptor/immunoglobulin G interaction using antibody and receptor variants. Biochemistry. 1995;34(45):14649–57. doi:10.1021/bi00045a005.
  • Oganesyan V, Damschroder MM, Cook KE, Li Q, Gao C, Wu H, Dall’acqua WF. Structural insights into neonatal Fc receptor-based recycling mechanisms. J Biol Chem. 2014;289(11):7812–24. doi:10.1074/jbc.M113.537563. PMID: 24469444.
  • 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(33):23514–24. doi:10.1074/jbc.M604292200. PMID: 16793771.
  • 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(2):157–59. doi:10.1038/nbt.1601. PMID: 20081867.
  • Robbie GJ, Criste R, Dall’acqua WF, Jensen K, Patel NK, Losonsky GA, Griffin MP. A novel investigational Fc-modified humanized monoclonal antibody, motavizumab-YTE, has an extended half-life in healthy adults. Antimicrob Agents Chemother. 2013;57(12):6147–53. doi:10.1128/AAC.01285-13. PMID: 24080653.
  • Booth BJ, Ramakrishnan B, Narayan K, Wollacott AM, Babcock GJ, Shriver Z, Viswanathan K. Extending human IgG half-life using structure-guided design. Mabs-austin. 2018;10:1098–110. doi:10.1080/19420862.2018.1490119. PMID: 29947573.
  • Liu R, Oldham RJ, Teal E, Beers SA, Cragg MS. Fc-engineering for modulated effector functions—improving antibodies for cancer treatment. Antibodies. 2020;9(4):64. doi:10.3390/antib9040064. PMID: 33212886.
  • Dall’acqua WF, 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. J Immunol. 2002;169(9):5171–80. doi:10.4049/jimmunol.169.9.5171. PMID: 12391234.
  • Mackness BC, Jaworski JA, Boudanova E, Park A, Valente D, Mauriac C, Pasquier O, Schmidt T, Kabiri M, Kandira A. et al. Antibody Fc engineering for enhanced neonatal Fc receptor binding and prolonged circulation half-life. Mabs-austin. 2019;11(7):1276–88. doi:10.1080/19420862.2019.1633883. PMID: 31216930.
  • 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-austin. 2015;7(2):331–43. doi:10.1080/19420862.2015.1008353. PMID: 25658443.
  • Gurbaxani BM, Morrison SL. Development of new models for the analysis of Fc–FcRn interactions. Mol Immunol. 2006;43(9):1379–89. doi:10.1016/j.molimm.2005.08.002. PMID: 16183124.
  • Rudnick SI, Adams GP. Affinity and avidity in antibody-based tumor targeting. Cancer Biother Radio. 2009;24(2):155–61. doi:10.1089/cbr.2009.0627. PMID: 19409036.
  • Diebolder CA, Beurskens FJ, de Jong RN, Koning RI, Strumane K, Lindorfer MA, Voorhorst M, Ugurlar D, Rosati S, Heck AJ. et al. Complement is activated by IgG hexamers assembled at the cell surface. Science. 2014;343(6176):1260–63. doi:10.1126/science.1248943. PMID: 24626930.
  • Rouge L, Chiang N, Steffek M, Kugel C, Croll TI, Tam C, Estevez A, Arthur CP, Koth CM, Ciferri C. et al. Structure of CD20 in complex with the therapeutic monoclonal antibody rituximab. Science. 2020;367(6483):1224–30. doi:10.1126/science.aaz9356. PMID: 32079680.
  • 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: MCP. 2015;14(1):148–61. doi:10.1074/mcp.M114.042044. PMID: 25378534.
  • 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(9):1469–77. doi:10.1124/dmd.111.039453. PMID: 21610128.
  • Yeung YA, Leabman MK, Marvin JS, Qiu J, Adams CW, Lien S, Starovasnik MA, Lowman HB. Engineering human IgG1 affinity to human neonatal Fc receptor: impact of affinity improvement on pharmacokinetics in primates. J Immunol. 2009;182(12):7663–71. doi:10.4049/jimmunol.0804182. PMID: 19494290.
  • 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-austin. 2013;5(4):576–86. doi:10.4161/mabs.24981. PMID: 23765230.
  • Muller-Landau H, Varela PF. Standard operation procedure for switchSENSE DRX systems. Eur Biophys J. 2021;50(3–4):389–400. doi:10.1007/s00249-021-01519-3. PMID: 33772617.
  • Langer A, Hampel PA, Kaiser W, Knezevic J, Welte T, Villa V, Maruyama M, Svejda M, Jahner S, Fischer F. et al. Protein analysis by time-resolved measurements with an electro-switchable DNA chip. Nat Commun. 2013;4(1):2099. doi:10.1038/ncomms3099. PMID: 23839273.
  • Knezevic J, Langer A, Hampel PA, Kaiser W, Strasser R, Rant U. Quantitation of affinity, avidity, and binding kinetics of protein analytes with a dynamically switchable biosurface. J Am Chem Soc. 2012;134(37):15225–28. doi:10.1021/ja3061276. PMID: 22946661.
  • Hampel PA, Strasser R, Fischer F, Rant U. Assembly and characterization of a slingshot DNA nanostructure for the analysis of bivalent and bispecific analytes with biosensors. Langmuir. 2018;34(49):14796–801. doi:10.1021/acs.langmuir.8b02124. PMID: 30269507.
  • Daub H, Traxler L, Ismajli F, Groitl B, Itzen A, Rant U. The trimer to monomer transition of tumor necrosis factor-alpha is a dynamic process that is significantly altered by therapeutic antibodies. Sci Rep. 2020;10(1):9265. doi:10.1038/s41598-020-66123-5. PMID: 32518229.
  • Mak S, Marszal A, Matscheko N, Rant U. Kinetic analysis of ternary and binary binding modes of the bispecific antibody emicizumab. Mabs-austin. 2023;15(1):2149053. doi:10.1080/19420862.2022.2149053. PMID: 36453702.
  • Qi T, Cao Y. In translation: FcRn across the therapeutic spectrum. Int J Mol Sci. 2021;22(6):3048. doi:10.3390/ijms22063048. PMID: 33802650.
  • Datta-Mannan A, Witcher DR, Tang Y, Watkins J, Jiang W, Wroblewski VJ. Humanized IgG1 variants with differential binding properties to the neonatal Fc receptor: relationship to pharmacokinetics in mice and primates. Drug Metab Dispos. 2007;35(1):86–94. doi:10.1124/dmd.106.011734. PMID: 17050651.
  • Vaughn DE, Bjorkman PJ. High-affinity binding of the neonatal Fc receptor to its IgG ligand requires receptor immobilization †. Biochemistry. 1997;36(31):9374–80. doi:10.1021/bi970841r.
  • Neuber T, Frese K, Jaehrling J, Jager S, Daubert D, Felderer K, Linnemann M, Hohne A, Kaden S, Kolln J. et al. Characterization and screening of IgG binding to the neonatal Fc receptor. Mabs-austin. 2014;6(4):928–42. doi:10.4161/mabs.28744. PMID: 24802048.
  • Soltermann F, Foley EDB, Pagnoni V, Galpin M, Benesch JLP, Kukura P, Struwe WB. Quantifying protein–protein interactions by molecular counting with mass photometry. Angew Chem Int Ed Engl. 2020;59(27):10774–79. doi:10.1002/anie.202001578. PMID: 32167227.
  • Feng Y, Gong R, Dimitrov DS. Design, expression and characterization of a soluble single-chain functional human neonatal Fc receptor. Protein Expr Purif. 2011;79(1):66–71. doi:10.1016/j.pep.2011.03.012. PMID: 21453773.
  • Grevys A, Nilsen J, Sand KMK, Daba MB, Oynebraten I, Bern M, McAdam MB, Foss S, Schlothauer T, Michaelsen TE. et al. A human endothelial cell-based recycling assay for screening of FcRn targeted molecules. Nat Commun. 2018;9(1):621. doi:10.1038/s41467-018-03061-x. PMID: 29434196.
  • Ober RJ, Martinez C, Vaccaro C, Zhou J, Ward ES. Visualizing the site and dynamics of IgG salvage by the MHC class I-related receptor, FcRn. J Immunol. 2004;172(4):2021–29. doi:10.4049/jimmunol.172.4.2021. PMID: 14764666.
  • Katsamba PS, Navratilova I, Calderon-Cacia M, Fan L, Thornton K, Zhu M, Bos TV, Forte C, Friend D, Laird-Offringa I. et al. Kinetic analysis of a high-affinity antibody/antigen interaction performed by multiple Biacore users. Anal Biochem. 2006;352(2):208–21. doi:10.1016/j.ab.2006.01.034. PMID: 16564019.
  • Tesar DB, Tiangco NE, Bjorkman PJ. Ligand valency affects transcytosis, recycling and intracellular trafficking mediated by the neonatal Fc receptor. Traffic. 2006;7(9):1127–42. doi:10.1111/j.1600-0854.2006.00457.x. PMID: 17004319.
  • Walters BT, Jensen PF, Larraillet V, Lin K, Patapoff T, Schlothauer T, Rand KD, Zhang J. Conformational destabilization of immunoglobulin G increases the low pH binding affinity with the neonatal Fc receptor. J Biol Chem. 2016;291(4):1817–25. doi:10.1074/jbc.m115.691568.
  • Santora LC, Kaymakcalan Z, Sakorafas P, Krull IS, Grant K. Characterization of noncovalent complexes of recombinant human monoclonal antibody and antigen using cation exchange, size exclusion chromatography, and BIAcore. Anal Biochem. 2001;299(2):119–29. doi:10.1006/abio.2001.5380. PMID: 11730333.
  • Kaymakcalan Z, Sakorafas P, Bose S, Scesney S, Xiong L, Hanzatian DK, Salfeld J, Sasso EH. Comparisons of affinities, avidities, and complement activation of adalimumab, infliximab, and etanercept in binding to soluble and membrane tumor necrosis factor. Clin Immunol. 2009;131(2):308–16. doi:10.1016/j.clim.2009.01.002. PMID: 19188093.
  • Vaughn DE, Bjorkman PJ. Structural basis of pH-dependent antibody binding by the neonatal Fc receptor. Struct Cell Press. 1998; doi:10.1016/s0969-2126(98)00008-2.
  • Fersht A. Enzyme structure and mechanism. 2nd ed. (NY): W H Freeman; 1985. p. 475.
  • Matthew JB, Gurd FR, Garcia-Moreno B, Flanagan MA, March KL, Shire SJ. pH-dependent processes in proteins. Crit Revi Biochem. 1985;18(2):91–197. doi:10.3109/10409238509085133. PMID: 3899508.
  • Piche-Nicholas NM, Avery LB, King AC, Kavosi M, Wang M, O’Hara DM, Tchistiakova L, Katragadda M. Changes in complementarity-determining regions significantly alter IgG binding to the neonatal Fc receptor (FcRn) and pharmacokinetics. Mabs-austin. 2018;10(1):81–94. doi:10.1080/19420862.2017.1389355. PMID: 28991504.
  • 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 USA. 2015;112(19):5997–6002. doi:10.1073/pnas.1408766112. PMID: 25918417.
  • Wang X, McKay P, Yee LT, Dutina G, Hass PE, Nijem I, Allison D, Cowan KJ, Lin K, Quarmby V. et al. Impact of SPR biosensor assay configuration on antibody: Neonatal Fc receptor binding data. Mabs-austin. 2017;9(2):319–32. doi:10.1080/19420862.2016.1261774. PMID: 28001487.
  • Souders CA, Nelson SC, Wang Y, Crowley AR, Klempner MS, Thomas W Jr. A novel in vitro assay to predict neonatal Fc receptor-mediated human IgG half-life. Mabs-austin. 2015;7(5):912–21. doi:10.1080/19420862.2015.1054585. PMID: 26018774.
  • Grevys A, Frick R, Mester S, Flem-Karlsen K, Nilsen J, Foss S, Sand KMK, Emrich T, Fischer JAA, Greiff V. et al. Antibody variable sequences have a pronounced effect on cellular transport and plasma half-life. iScience. 2022;25(2):103746. doi:10.1016/j.isci.2022.103746. PMID: 35118359.
  • Arinaga K, Rant U, Knezevic J, Pringsheim E, Tornow M, Fujita S, Abstreiter G, Yokoyama N. Controlling the surface density of DNA on gold by electrically induced desorption. Biosens Bioelectron. 2007;23(3):326–31. doi:10.1016/j.bios.2007.04.012. PMID: 17560778.
  • Rant U, Arinaga K, Scherer S, Pringsheim E, Fujita S, Yokoyama N, Tornow M, Abstreiter G. Switchable DNA interfaces for the highly sensitive detection of label-free DNA targets. Proc Natl Acad Sci USA. 2007;104(44):17364–69. doi:10.1073/pnas.0703974104.