Interactions of the anti-FcRn monoclonal antibody, rozanolixizumab, with Fcγ receptors and functional impact on immune cells in vitro

References

• Nimmerjahn F, Ravetch J. Fcgamma receptors as regulators of immune responses. Nat Rev Immunol. 2008 Jan;8(1):34–12. doi:10.1038/nri2206.
   PubMed Web of Science ®Google Scholar
• Shock A, Humphreys D, Nimmerjahn F. Dissecting the mechanism of action of intravenous immunoglobulin in human autoimmune disease: lessons from therapeutic modalities targeting Fcγ receptors. J Allergy Clin Immunol. 2020 Sep;146(3):492–500. doi:10.1016/j.jaci.2020.06.036.
   PubMed Web of Science ®Google Scholar
• Patel D, Bussel J. Neonatal Fc receptor in human immunity: function and role in therapeutic intervention. J Allergy Clin Immunol. 2020 Sep;146(3):467–78. doi:10.1016/j.jaci.2020.07.015.
   PubMed Web of Science ®Google Scholar
• Pyzik M, Kozicky LK, Gandhi AK, Blumberg RS. The therapeutic age of the neonatal Fc receptor. Nat Rev Immunol. 2023 Feb;1:1–18.
   Google Scholar
• 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 Oct 5;217(10): e20200359. doi: 10.1084/jem.20200359.
   PubMed Web of Science ®Google Scholar
• Bril V, Drużdż A, Grosskreutz J, Habib AA, Mantegazza R, Sacconi S, Utsugisawa K, Vissing J, Vu T, Boehnlein M, et al. Safety and efficacy of rozanolixizumab in patients with generalised myasthenia gravis (MycarinG): a randomised, double-blind, placebo-controlled, adaptive phase 3 study. Lancet Neurol. 2023 May;22(5):383–94. doi:10.1016/S1474-4422(23)00077-7.
   PubMed Web of Science ®Google Scholar
• Howard JF Jr, Bril V, Vu T, Karam C, Peric S, Margania T, Murai H, Bilinska M, Shakarishvili R, Smilowski M, et al. Safety, efficacy, and tolerability of efgartigimod in patients with generalised myasthenia gravis (ADAPT): a multicentre, randomised, placebo-controlled, phase 3 trial. Lancet Neurol. 2021 Jul;20(7):526–36. doi:10.1016/S1474-4422(21)00159-9.
   PubMed Web of Science ®Google Scholar
• Vaccaro C, Zhou J, Ober RJ, Ward ES. Engineering the Fc region of immunoglobulin G to modulate in vivo antibody levels. Nat Biotechnol. 2005 Oct;23(10):1283–88. doi:10.1038/nbt1143.
   PubMed Web of Science ®Google Scholar
• Smith B, Kiessling A, Lledo-Garcia R, Dixon KL, Christodoulou L, Catley MC, Atherfold P, D’Hooghe LE, Finney H, Greenslade K, et al. Generation and characterization of a high affinity anti-human FcRn antibody, rozanolixizumab, and the effects of different molecular formats on the reduction of plasma IgG concentration. MAbs. 2018 Oct;10(7):1111–30. doi:10.1080/19420862.2018.1505464.
   PubMed Web of Science ®Google Scholar
• Kiessling P, Lledo-Garcia R, Watanabe S, Langdon G, Tran D, Bari M, Christodoulou L, Jones E, Price G, Smith B, et al. The FcRn inhibitor rozanolixizumab reduces human serum IgG concentration: a randomized phase 1 study. Sci Transl Med. 2017 Nov1;9(414):eaan1208. doi:10.1126/scitranslmed.aan1208.
   PubMed Web of Science ®Google Scholar
• Ulrichts P, Guglietta A, Dreier T, van Bragt T, Hanssens V, Hofman E, Vankerckhoven B, Verheesen P, Ongenae N, Lykhopiy V, et al. Neonatal Fc receptor antagonist efgartigimod safely and sustainably reduces IgGs in humans. J Clin Invest. 2018 Oct 1;128(10):4372–86. doi: 10.1172/JCI97911.
   PubMed Web of Science ®Google Scholar
• Bruhns P, Iannascoli B, England P, Mancardi DA, Fernandez N, Jorieux S, Daëron M. Specificity and affinity of human Fcgamma receptors and their polymorphic variants for human IgG subclasses. Blood. 2009 Apr 16;113(16):3716–25. doi:10.1182/blood-2008-09-179754.
   PubMed Web of Science ®Google Scholar
• Bruhns P. Properties of mouse and human IgG receptors and their contribution to disease models. Blood. 2012 Jun 14;119(24):5640–49. doi:10.1182/blood-2012-01-380121.
   PubMed Web of Science ®Google Scholar
• Tao MH, Smith RI, Morrison SL. Structural features of human immunoglobulin G that determine isotype-specific differences in complement activation. J Exp Med. 1993;178(2):661–66. doi:10.1084/jem.178.2.661.
   PubMed Web of Science ®Google Scholar
• Wilkinson I, Anderson S, Fry J, Julien LA, Neville D, Qureshi O, Watts G, Hale G. Fc-engineered antibodies with immune effector functions completely abolished. PLOS ONE. 2021 Dec 21;16(12):e0260954. doi:10.1371/journal.pone.0260954.
   PubMed Web of Science ®Google Scholar
• Grevys A, Bern M, Foss S, Bratlie DB, Moen A, Gunnarsen KS, Aase A, Michaelsen TE, Sandlie I, Andersen JT. Fc engineering of human IgG1 for altered binding to the neonatal Fc receptor affects Fc effector functions. J Immunol. 2015 Jun 1;194(11):5497–508. doi:10.4049/jimmunol.1401218.
   PubMed Web of Science ®Google Scholar
• Daëron M, Duc HT, Kanellopoulos J, Le Bouteiller P, Kinsky R, Voisin GA. Allogenic mast cell degranulation induced by histocompatibility antibodies: an in vitro model of transplantation anaphylaxis. Cell Immunol. 1975 Dec;20(2):133–55. doi:10.1016/0008-8749(75)90092-1.
   PubMed Web of Science ®Google Scholar
• Voisin GA. Role of antibody classes in the regulatory facilitation reaction. Immunol Rev. 1980;49(1):3–59. doi:10.1111/j.1600-065X.1980.tb00425.x.
   PubMedGoogle Scholar
• Kurlander RJ. Blockade of Fc receptor-mediated binding to U-937 cells by murine monoclonal antibodies directed against a variety of surface antigens. J Immunol. 1 July 1983;131(1):140–47. doi:10.4049/jimmunol.131.1.140.
   PubMed Web of Science ®Google Scholar
• Zhu X, Meng G, Dickinson BL, Li X, Mizoguchi E, Miao L, Wang Y, Robert C, Wu B, Smith PD, et al. MHC class I-related neonatal Fc receptor for IgG is functionally expressed in monocytes, intestinal macrophages, and dendritic cells. J Immunol.2001 Mar 1;166(5):3266–76. doi:10.4049/jimmunol.166.5.3266.
   PubMed Web of Science ®Google Scholar
• Rowley TF, Peters SJ, Aylott M, Griffin R, Davies NL, Healy LJ, Cutler RM, Eddleston A, Pither TL, Sopp JM, et al. Engineered hexavalent Fc proteins with enhanced Fc-gamma receptor avidity provide insights into immune-complex interactions. Commun Biol. 2018 Sep 14;1(1):146. doi:10.1038/s42003-018-0149-9.
   PubMedGoogle Scholar
• Bruhns P, Jönsson F. Mouse and human FcR effector functions. Immunol Rev. 2015 Nov;268(1):25–51. doi:10.1111/imr.12350.
   PubMed Web of Science ®Google Scholar
• Bril V, Benatar M, Andersen H, Vissing J, Brock M, Greve B, Kiessling P, Woltering F, Griffin L, Van den Bergh P, et al. Efficacy and safety of rozanolixizumab in moderate to severe generalized myasthenia gravis: a phase 2 randomized control trial. Neurology. 2021 Feb 9; 96(6):e853–e865. doi:10.1212/WNL.0000000000011108.
   PubMed Web of Science ®Google Scholar
• van Mirre E, Teeling JL, van der Meer JW, Bleeker WK, Hack CE. Monomeric IgG in intravenous Ig preparations is a functional antagonist of FcgammaRII and FcgammaRIIIb. J Immunol. 2004 Jul 1;173(1):332–39. doi:10.4049/jimmunol.173.1.332.
   PubMed Web of Science ®Google Scholar
• Junker F, Krishnarajah S, Qureshi O, Humphreys D, Fallah-Arani F. A simple method for measuring immune complex-mediated, Fc gamma receptor dependent antigen-specific activation of primary human T cells. J Immunol Methods. 2018 Mar;454:32–39. doi:10.1016/j.jim.2017.12.002.
   PubMed Web of Science ®Google Scholar
• Liu R, Oldham RJ, Teal E, Beers SA, Cragg MS. Fc-engineering for modulated effector functions - improving antibodies for cancer treatment. Antibodies (Basel). 2020 Nov 17;9(4):64. doi:10.3390/antib9040064.
   PubMedGoogle Scholar
• Wang W, Chen Q. Antigen improves binding of IgGs to FcγRs in SPR analysis. Anal Biochem. 2022 Mar 1;640:114411. doi:10.1016/j.ab.2021.114411.
   PubMed Web of Science ®Google Scholar
• Latvala S, Jacobsen B, Otteneder MB, Herrmann A, Kronenberg S. Distribution of FcRn across species and tissues. J Histochem Cytochem. 2017 Jun;65(6):321–33. doi:10.1369/0022155417705095.
   PubMed Web of Science ®Google Scholar
• Gan Z, Ram S, Vaccaro C, Ober RJ, Ward ES. Analyses of the recycling receptor, FcRn, in live cells reveal novel pathways for lysosomal delivery. Traffic. 2009 May;10(5):600–14. doi:10.1111/j.1600-0854.2009.00887.x.
   PubMed Web of Science ®Google Scholar
• Wu Z, Simister NE. Tryptophan- and dileucine-based endocytosis signals in the neonatal Fc receptor. J Biol Chem. 2001 Feb 16;276(7):5240–47. doi:10.1074/jbc.M006684200.
   PubMed Web of Science ®Google Scholar
• Li Y, Lee PY, Kellner ES, Paulus M, Switanek J, Xu Y, Zhuang H, Sobel ES, Segal MS, Satoh M, et al. Monocyte surface expression of Fcgamma receptor RI (CD64), a biomarker reflecting type-I interferon levels in systemic lupus erythematosus. Arthritis Res Ther. 2010;12(3):R90. doi:10.1186/ar3017.
   PubMed Web of Science ®Google Scholar
• Holtrop T, Budding K, Brandsma AM, Leusen JHW. Targeting the high affinity receptor, FcγRI, in autoimmune disease, neuropathy, and cancer. Immunother Adv. 2022 May 28;2(1):ltac011. doi:10.1093/immadv/ltac011.
   PubMedGoogle Scholar
• Chalayer E, Gramont B, Zekre F, Goguyer-Deschaumes R, Waeckel L, Grange L, Paul S, Chung AW, Killian M. Fc receptors gone wrong: a comprehensive review of their roles in autoimmune and inflammatory diseases. Autoimmun Rev. 2022 Mar;21(3):103016. doi:10.1016/j.autrev.2021.103016.
   PubMed Web of Science ®Google Scholar
• Kikuchi-Taura A, Yura A, Tsuji S, Ohshima S, Kitatoube A, Shimizu T, Nii T, Katayama M, Teshigawara S, Yoshimura M, et al. Monocyte CD64 expression as a novel biomarker for the disease activity of systemic lupus erythematosus. Lupus. 2015 Sep;24(10):1076–80. doi:10.1177/0961203315579093.
   PubMed Web of Science ®Google Scholar
• Mancardi DA, Albanesi M, Jönsson F, Iannascoli B, Van Rooijen N, Kang X, England P, Daëron M, Bruhns P. The high-affinity human IgG receptor FcγRI (CD64) promotes IgG-mediated inflammation, anaphylaxis, and antitumor immunotherapy. Blood. 2013 Feb 28;121(9):1563–73. doi:10.1182/blood-2012-07-442541.
   PubMed Web of Science ®Google Scholar
• Wijngaarden S, van de Winkel JG, Jacobs KM, Bijlsma JW, Lafeber FP, van Roon JA. A shift in the balance of inhibitory and activating Fcγ receptors on monocytes toward the inhibitory Fcγ receptor IIb is associated with prevention of monocyte activation in rheumatoid arthritis. Arthritis & Rheum. 2004;50(12):3878–87. doi:10.1002/art.20672.
   PubMedGoogle Scholar
• Fitzpatrick EA, Wang J, Strome SE. Engineering of Fc multimers as a protein therapy for autoimmune disease. Front Immunol. 2020 Mar 25;11:496. doi:10.3389/fimmu.2020.00496.
   PubMed Web of Science ®Google Scholar
• Daëron M. Fc receptor biology. Ann Rev Immunol. 1997;15(1):203–34. doi:10.1146/annurev.immunol.15.1.203.
   PubMedGoogle Scholar
• 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 Jun 14;108(24):9927–32. doi: 10.1073/pnas.1019037108.
   PubMed Web of Science ®Google Scholar
• Liu X, Lu L, Yang Z, Palaniyandi S, Zeng R, Gao LY, Mosser DM, Roopenian DC, Zhu X. The neonatal FcR-mediated presentation of immune-complexed antigen is associated with endosomal and phagosomal pH and antigen stability in macrophages and dendritic cells. J Immunol. 2011 Apr 15;186(8):4674–86. doi:10.4049/jimmunol.1003584.
   PubMed Web of Science ®Google Scholar
• Haraya K, Tachibana T. Simple approach to accurately predict pharmacokinetics of therapeutic monoclonal antibodies after subcutaneous injection in humans. Clin Pharmacokinet. 2021 Jan;60(1):111–20. doi:10.1007/s40262-020-00917-8.
   PubMed Web of Science ®Google Scholar