FcRn rescues recombinant factor VIII Fc fusion protein from a VWF independent FVIII clearance pathway in mouse hepatocytes

PLoS ONE

Volumn 10, Issue 4, 2015, Pages

  Van Der Flier, Arjan ^a   Liu, Zhan ^a   Tan, Siyuan ^a   Chen, Kai ^a   Drager, Douglas ^a   Liu, Tongyao ^a   Patarroyo White, Susannah ^a   Jiang, Haiyan ^a   Light, David R ^a  

^a BIOGEN   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

FC RECEPTOR; HYBRID PROTEIN; NEONATAL FC RECEPTOR; RECOMBINANT BLOOD CLOTTING FACTOR 8; RECOMBINANT BLOOD CLOTTING FACTOR 8 FC FUSION PROTEIN; UNCLASSIFIED DRUG; VON WILLEBRAND FACTOR; BLOOD CLOTTING FACTOR 8; FC RECEPTOR, NEONATAL; HLA ANTIGEN CLASS 1; SCAVENGER RECEPTOR;

ANIMAL CELL; ANIMAL EXPERIMENT; ANIMAL TISSUE; ARTICLE; CHIMERA; CONTROLLED STUDY; DRUG BIOAVAILABILITY; DRUG CLEARANCE; DRUG DEGRADATION; DRUG DISTRIBUTION; DRUG HALF LIFE; DRUG PROTEIN BINDING; DRUG UPTAKE; ENDOTHELIUM CELL; IMMUNOHISTOCHEMISTRY; INTERNALIZATION; KUPFFER CELL; LIVER CELL; LIVER CLEARANCE; LIVER SINUSOID; MACROPHAGE; MALE; MOUSE; NONHUMAN; PROTEIN EXPRESSION; SOMATIC CELL; ANIMAL; KNOCKOUT MOUSE; METABOLISM; PHYSIOLOGY; TISSUE DISTRIBUTION;

MUS;

ANIMALS; FACTOR VIII; HEPATOCYTES; HISTOCOMPATIBILITY ANTIGENS CLASS I; MICE; MICE, KNOCKOUT; RECEPTORS, FC; RECEPTORS, SCAVENGER; RECOMBINANT FUSION PROTEINS; TISSUE DISTRIBUTION; VON WILLEBRAND FACTOR;

EID: 84928485382     PISSN: None     EISSN: 19326203     Source Type: Journal    
DOI: 10.1371/journal.pone.0124930     Document Type: Article

References (71)

1. Berntorp E, Shapiro AD. Modern haemophilia care. Lancet. 2012 Apr 14; 379(9824):1447-56. doi: 10.1016/S0140-6736(11)61139-2 PMID: 22456059
2. Dumont JA, Liu T, Low SC, Zhang X, Kamphaus G, Sakorafas P, et al. Prolonged activity of a recombinant factor VIII-Fc fusion protein in hemophilia A mice and dogs. Blood. 2012 Mar 29; 119(13):3024-30. doi: 10.1182/blood-2011-08-367813 PMID: 22246033
3. Mahlangu J, Powell JS, Ragni MV, Chowdary P, Josephson NC, Pabinger I, et al. Phase 3 study of recombinant factor VIII Fc fusion protein in severe hemophilia A. Blood. 2014 Jan 16; 123(3):317-25. doi: 10.1182/blood-2013-10-529974 PMID: 24227821
4. Powell JS, Josephson NC, Quon D, Ragni MV, Cheng G, li E, et al. Safety and prolonged activity of recombinant factor VIII Fc fusion protein in hemophilia A patients. Blood. 2012 Mar 29; 119(13):3031-7. doi: 10.1182/blood-2011-09-382846 PMID: 22223821
5. Roopenian DC, Akilesh S. FcRn: the neonatal Fc receptor comes of age. Nat Rev Immunol. 2007 Sep; 7(9):715-25. PMID: 17703228
6. Israel EJ, Wilsker DF, Hayes KC, Schoenfeld D, Simister NE. Increased clearance of IgG in mice that lack beta 2-microglobulin: possible protective role of FcRn. Immunology. 1996 Dec; 89(4):573-8. PMID: 9014824
7. Kuo TT, Aveson VG. Neonatal Fc receptor and IgG-based therapeutics. MAbs. 2011 Sep 1; 3(5):422-30. doi: 10.4161/mabs.3.5.16983 PMID: 22048693
8. Kuo TT, Baker K, Yoshida M, Qiao S-W, Aveson VG, Lencer WI, et al. Neonatal Fc receptor: from immunity to therapeutics. J Clin Immunol. 2010 Nov; 30(6):777-89. doi: 10.1007/s10875-010-9468-4 PMID: 20886282
9. Rath T, Baker K, Dumont JA, Peters RT, jiang H, Qiao S-W, et al. Fc-fusion proteins and FcRn: structural insights for longer-lasting and more effective therapeutics. Critical Reviews in Biotechnology. 2013 Oct 24;:1-20.
10. Baker K, Rath T, Lencer WI, Fiebiger E, Blumberg RS. Cross-presentation of IgG-containing immune complexes. Cell Mol Life Sci. 2013 Apr; 70(8):1319-34. doi: 10.1007/s00018-012-1100-8 PMID: 22847331
11. Nakata K, Kobayashi K, Ishikawa Y, Yamamoto M, Funada Y, Kotani Y, et al. The transfer of maternal antigen-specific IgG regulates the development of allergic airway inflammation early in life in an FcRn-dependent manner. Biochemical and Biophysical Research Communications. 2010 Apr 30; 395 (2):238-43. doi: 10.1016/j.bbrc.2010.03.170 PMID: 20362552
12. Akilesh S, Christianson GJ, Roopenian DC, Shaw AS. Neonatal FcR expression in bone marrow-derived cells functions to protect serum IgG from catabolism. J Immunol. 2007 Oct 1; 179(7):4580-8. PMID: 17878355
13. Qiao SW, Kobayashi K, Johansen FE, Sollid LM, Andersen JT, Milford E, et al. Dependence of antibody-mediated presentation of antigen on FcRn. Proceedings of the National Academy of Sciences. 2008 ed. 2008 Jul 8; 105(27):9337-42. doi: 10.1073/pnas.0801717105 PMID: 18599440
14. Kobayashi K, Qiao S-W, Yoshida M, Baker K, Lencer WI, Blumberg RS. An FcRn-dependent role for anti-flagellin immunoglobulin G in pathogenesis of colitis in mice. Gastroenterology. 2009 Nov; 137 (5):1746-56.e1. doi: 10.1053/j.gastro.2009.07.059 PMID: 19664634
15. Montoyo HP, Vaccaro C, Hafner M, Ober RJ, Mueller W, Ward ES. Conditional deletion of the MHC class I-related receptor FcRn reveals the sites of IgG homeostasis in mice. Proceedings of the National Academy of Sciences. 2009 Feb 24; 106(8):2788-93. doi: 10.1073/pnas.0810796106 PMID: 19188594
16. Peters RT, Low SC, Kamphaus GD, Dumont JA, Amari JV, Lu Q, et al. Prolonged activity of factor IX as a monomeric Fc fusion protein. Blood. 2010 ed. 2010 Mar 11; 115(10):2057-64. doi: 10.1182/blood-2009-08-239665 PMID: 20056791
17. Fahs SA, Hille MT, Shi Q, Weiler H, Montgomery RR. A conditional knockout mouse model reveals endothelial cells as the principal and possibly exclusive source of plasma factor VIII. Blood. 2014 Jun 12; 123(24):3706-13. doi: 10.1182/blood-2014-02-555151 PMID: 24705491
18. Everett LA, Cleuren ACA, Khoriaty RN, Ginsburg D. Murine coagulation factor VIII is synthesized in endothelial cells. Blood. 2014 Jun 12; 123(24):3697-705. doi: 10.1182/blood-2014-02-554501 PMID: 24719406
19. Butenas S, Parhami-Seren B, Undas A, Fass DN, Mann KG. The "normal" factor VIII concentration in plasma. Thromb Res. 2010 Aug; 126(2):119-23. doi: 10.1016/j.thromres.2010.04.004 PMID: 20451961
20. Vlot AJ, Koppelman SJ, van den Berg MH, Bouma BN, Sixma JJ. The affinity and stoichiometry of binding of human factor VIII to von Willebrand factor. Blood. 1995 Jun 1; 85(11):3150-7. PMID: 7756647
21. Borchiellini A, Fijnvandraat K, Cate ten JW, Pajkrt D, van Deventer SJ, Pasterkamp G, et al. Quantitative analysis of von Willebrand factor propeptide release in vivo: effect of experimental endotoxemia and administration of 1-deamino-8-D-arginine vasopressin in humans. Blood. 1996 Oct 15; 88 (8):2951-8. PMID: 8874191
22. Kanaji S, Fahs SA, Shi Q, Haberichter SL, Montgomery RR. Contribution of platelet vs. endothelial VWF to platelet adhesion and hemostasis. J Thromb Haemost. 2012 Aug; 10(8):1646-52. doi: 10.1111/j.1538-7836.2012.04797.x PMID: 22642380
23. Fay PJ, Coumans JV, Walker FJ. von Willebrand factor mediates protection of factor VIII from activated protein C-catalyzed inactivation. J Biol Chem. 1991 Feb 5; 266(4):2172-7. PMID: 1846615
24. Koedam JA, Meijers JC, Sixma JJ, Bouma BN. Inactivation of human factor VIII by activated protein C. Cofactor activity of protein S and protective effect of von Willebrand factor. Journal of Clinical Investigation. 1988 Oct; 82(4):1236-43. PMID: 2971673
25. Terraube V, O'Donnell J S, Jenkins PV. Factor VIII and von Willebrand factor interaction: biological, clinical and therapeutic importance. Haemophilia. 2010 Jan; 16(1):3-13. doi: 10.1111/j.1365-2516.2009.02005.x PMID: 19473409
26. Shapiro AD, Ragni MV, Kulkarni R, Oldenberg J, Srivastava A, Quon DV, et al. Recombinant factor VIII Fc fusion protein: extended-interval dosing maintains low bleeding rates and correlates with von Willebrand factor levels. J Thromb Haemost. 2014 Nov; 12(11):1788-800. doi: 10.1111/jth.12723 PMID: 25196897
27. Lillicrap D. von Willebrand disease: advances in pathogenetic understanding, diagnosis, and therapy. Blood. 2013 Nov 28; 122(23):3735-40. doi: 10.1182/blood-2013-06-498303 PMID: 24065240
28. Gadisseur A, Hermans C, Berneman Z, Schroyens W, Deckmyn H, Michiels JJ. Laboratory diagnosis and molecular classification of von Willebrand disease. Acta Haematol. 2009; 121(2- 3):71-84. doi: 10.1159/000226423 PMID: 19556751
29. Lenting PJ, Pegon JN, Christophe OD, Denis CV. Factor VIII and von Willebrand factor - too sweet for their own good. Haemophilia. 2010 Jul; 16 Suppl 5:194-9. doi: 10.1111/j.1365-2516.2010.02320.x PMID: 20590881
30. Lenting PJ, Christophe OD, Guegen P. The disappearing act of factor VIII. Haemophilia. 2010 May; 16 (102):6-15. doi: 10.1111/j.1365-2516.2008.01864.x PMID: 18771423
31. Lenting PJ, VANS CJ, Denis CV. Clearance mechanisms of von Willebrand factor and factor VIII. J Thromb Haemost. 2007 Jul; 5(7):1353-60. PMID: 17425686
32. Bovenschen N, Mertens K, Hu L, Havekes LM, van Vlijmen BJ. LDL receptor cooperates with LDL receptor-related protein in regulating plasma levels of coagulation factor VIII in vivo. Blood. 2005 Aug 1; 106(3):906-12. PMID: 15840700
33. Sarafanov AG, Ananyeva NM, Shima M, Saenko EL. Cell surface heparan sulfate proteoglycans participate in factor VIII catabolism mediated by low density lipoprotein receptor-related protein. J Biol Chem. 2001 Apr 13; 276(15):11970-9. PMID: 11278379
34. Smith NL, Chen M-H, Dehghan A, Strachan DP, Basu S, Soranzo N, et al. Novel associations of multiple genetic loci with plasma levels of factor VII, factor VIII, and von Willebrand factor: The CHARGE (Cohorts for Heart and Aging Research in Genome Epidemiology) Consortium. Circulation. 2010 Mar 30; 121(12):1382-92. doi: 10.1161/CIRCULATIONAHA.109.869156 PMID: 20231535
35. Rydz N, Swystun LL, Notley C, Paterson AD, Riches JJ, Sponagle K, et al. The C-type lectin receptor CLEC4M binds, internalizes, and clears von Willebrand factor and contributes to the variation in plasma von Willebrand factor levels. Blood. 2013 Jun 27; 121(26):5228-37. doi: 10.1182/blood-2012-10-457507 PMID: 23529928
36. Antoni G, Oudot-Mellakh T, Dimitromanolakis A, Germain M, Cohen W, Wells P, et al. Combined analysis of three genome-wide association studies on vWF and FVIII plasma levels. BMC Med Genet. 2011; 12:102. doi: 10.1186/1471-2350-12-102 PMID: 21810271
37. van Schooten CJ, Shahbazi S, Groot E, Oortwijn BD, van den Berg BM, Denis CV, et al. Macrophages contribute to the cellular uptake of von Willebrand factor and factor VIII in vivo. Blood. 2008 Sep 1; 112 (5):1704-12. doi: 10.1182/blood-2008-01-133181 PMID: 18559674
38. Navarrete AM, Dasgupta S, Delignat S, Caligiuri G, Christophe OD, Bayry J, et al. Splenic marginal zone antigen-presenting cells are critical for the primary allo-immune response to therapeutic factor VIII in hemophilia A. J Thromb Haemost. 2009 Nov; 7(11):1816-23. doi: 10.1111/j.1538-7836.2009.03571.x PMID: 19682235
39. Medesan C, Matesoi D, Radu C, Ghetie V, Ward ES. Delineation of the amino acid residues involved in transcytosis and catabolism of mouse IgG1. J Immunol. 1997 Mar 1; 158(5):2211-7. PMID: 9036967
40. Shields RL, Namenuk AK, Hong K, Meng YG, Rae J, Briggs J, et al. High resolution mapping of the binding site on human IgG1 for Fc gamma RI, Fc gamma RII, Fc gamma RIII, and FcRn and design of IgG1 variants with improved binding to the Fc gamma R. J Biol Chem. 2001 Mar 2; 276(9):6591-604. PMID: 11096108
41. Bi L, Lawler AM, Antonarakis SE, High KA, Gearhart JD, Kazazian HHJ. Targeted disruption of the mouse factor VIII gene produces a model of haemophilia A. Nat Genet. 1995 May; 10(1):119-21. PMID: 7647782
42. Denis C, Methia N, Frenette PS, Rayburn H, Ullman-Cullere M, Hynes RO, et al. A mouse model of severe von Willebrand disease: defects in hemostasis and thrombosis. Proc Natl Acad Sci USA. 1998 Aug 4; 95(16):9524-9. PMID: 9689113
43. Roopenian DC, Christianson GJ, Sproule TJ, Brown AC, Akilesh S, Jung N, et al. The MHC class I-like IgG receptor controls perinatal IgG transport, IgG homeostasis, and fate of IgG-Fc-coupled drugs. J Immunol. 2003 Apr 1; 170(7):3528-33. PMID: 12646614
44. National Research Council (US) Committee for the Update of the Guide for the Care and Use of Laboratory Animals. Guide for the Care and Use of Laboratory Animals. 8 ed. Washington (DC): National Academies Press (US); 2011.
45. Bolton AE, Hunter WM. The labelling of proteins to high specific radioactivities by conjugation to a 125I-containing acylating agent. Biochem J. 1973 Jul; 133(3):529-39. PMID: 4733239
46. Klein I, Cornejo JC, Polakos NK, John B, Wuensch SA, Topham DJ, et al. Kupffer cell heterogeneity: functional properties of bone marrow derived and sessile hepatic macrophages. Blood. 2007 Dec 1; 110(12):4077-85. PMID: 17690256
47. Mei B, Pan C, Jiang H, Tjandra H, Strauss J, Chen Y, et al. Rational design of a fully active, long-acting PEGylated factor VIII for hemophilia A treatment. Blood. 2010 ed. 2010 Jul 15; 116(2):270-9. doi: 10.1182/blood-2009-11-254755 PMID: 20194895
48. Stennicke HR, Kjalke M, Karpf DM, Balling KW, Johansen PB, Elm T, et al. A novel B-domain O-glyco-PEGylated FVIII (N8-GP) demonstrates full efficacy and prolonged effect in hemophilic mice models. Blood. 2013 Mar 14; 121(11):2108-16. doi: 10.1182/blood-2012-01-407494 PMID: 23335368
49. Tang L, Leong L, Sim D, Ho E, Gu JM, Schneider D, et al. von Willebrand factor contributes to longer half-life of PEGylated factor VIII in vivo. Haemophilia. 2013 Jul; 19(4):539-45. doi: 10.1111/hae.12116 PMID: 23534820
50. Froh M, Konno A, Thurman RG. Isolation of liver Kupffer cells. Curr Protoc Toxicol. 2003 Feb;Chapter 14:Unit14.4.
51. Shi Q, Kuether EL, Schroeder JA, Fahs SA, Montgomery RR. Intravascular recovery of VWF and FVIII following intraperitoneal injection and differences from intravenous and subcutaneous injection in mice. Haemophilia. 2012 Jul; 18(4):639-46. doi: 10.1111/j.1365-2516.2011.02735.x PMID: 22221819
52. Christianson GJ, Sun VZ, Akilesh S, Pesavento E, Proetzel G, Roopenian DC. Monoclonal antibodies directed against human FcRn and their applications. MAbs. 2012 Mar 1; 4(2):208-16. doi: 10.4161/mabs.4.2.19397 PMID: 22453095
53. Nonaka H, Tanaka M, Suzuki K, Miyajima A. Development of murine hepatic sinusoidal endothelial cells characterized by the expression of hyaluronan receptors. Dev Dyn. 2007 Aug; 236(8):2258-67. PMID: 17626278
54. Kinoshita M, Uchida T, Sato A, Nakashima M, Nakashima H, Shono S, et al. Characterization of two F4/80-positive Kupffer cell subsets by their function and phenotype in mice. J Hepatol. 2010 Nov; 53 (5):903-10. doi: 10.1016/j.jhep.2010.04.037 PMID: 20739085
55. Liu ZL, Bou-Assaf G, Zhang M, Goodman A, Chiu P-L, Chambers M, et al. Assessing Structure-Activity Relationships in FVIII By Integration of Structural, Biophysical, and Biochemical Data Obtained with Anti-FVIII Antibodies. Blood. 2014 Dec 5; 124(21):4223-3.
56. Denis CV, Christophe OD, Oortwijn BD, Lenting PJ. Clearance of von Willebrand factor. Thromb Haemost. 2008 Feb; 99(2):271-8. doi: 10.1160/TH07-10-0629 PMID: 18278174
57. Sodetz JM, Pizzo SV, McKee PA. Relationship of sialic acid to function and in vivo survival of human factor VIII/von Willebrand factor protein. J Biol Chem. 1977 Aug 10; 252(15):5538-46. PMID: 301877
58. Gopalakrishnan R, Hedner U, Ghosh S, Nayak RC, Allen TC, Pendurthi UR, et al. Bio-distribution of pharmacologically administered recombinant factor VIIa (rFVIIa). J Thromb Haemost. 2010 Feb; 8 (2):301-10. doi: 10.1111/j.1538-7836.2009.03696.x PMID: 19943873
59. Chang C-H, Chou T-K, Yang C-Y, Chang T-J, Wu Y-H, Lee T-W. Biodistribution and pharmacokinetics of transgenic pig-produced recombinant human factor IX (rhFIX) in rats. In Vivo. 2008 Nov; 22(6):693-7. PMID: 19180993
60. Gui T, Lin H-F, Jin D-Y, Hoffman M, Straight DL, Roberts HR, et al. Circulating and binding characteristics of wild-type factor IX and certain Gla domain mutants in vivo. Blood. 2002 Jul 1; 100(1):153-8. PMID: 12070021
61. Rastegarlari G, Pegon JN, Casari C, Odouard S, Navarrete A-M, Saint-Lu N, et al. Macrophage LRP1 contributes to the clearance of von Willebrand factor. Blood. 2012 Mar 1; 119(9):2126-34. doi: 10.1182/blood-2011-08-373605 PMID: 22234691
62. Kontermann RE. Strategies for extended serum half-life of protein therapeutics. Current Opinion in Biotechnology. 2011 Dec; 22(6):868-76. doi: 10.1016/j.copbio.2011.06.012 PMID: 21862310
63. Mordenti J, Osaka G, Garcia K, Thomsen K, Licko V, Meng G. Pharmacokinetics and interspecies scaling of recombinant human factor VIII. Toxicol Appl Pharmacol. 1996 Jan; 136(1):75-8. PMID: 8560482
64. Federici AB. The factor VIII/von Willebrand factor complex: basic and clinical issues. Haematologica. 2003 Jun; 88(6):EREP02.
65. Schneider SW, Nuschele S, Wixforth A, Gorzelanny C, Alexander-Katz A, Netz RR, et al. Shear-induced unfolding triggers adhesion of von Willebrand factor fibers. Proc Natl Acad Sci USA. 2007 May 8; 104(19):7899-903. PMID: 17470810
66. Dong JF. Cleavage of ultra-large von Willebrand factor by ADAMTS-13 under flow conditions. J Thromb Haemost. 2005 Aug; 3(8):1710-6. PMID: 16102037
67. Ogawara K, Yoshida M, Higaki K, Kimura T, Shiraishi K, Nishikawa M, et al. Hepatic uptake of polystyrene microspheres in rats: effect of particle size on intrahepatic distribution. J Control Release. 1999 May 1; 59(1):15-22. PMID: 10210718
68. Sarin H. Physiologic upper limits of pore size of different blood capillary types and another perspective on the dual pore theory of microvascular permeability. J Angiogenes Res. 2010; 2:14. doi: 10.1186/2040-2384-2-14 PMID: 20701757
69. Wisse E, Jacobs F, Topal B, Frederik P, De Geest B. The size of endothelial fenestrae in human liver sinusoids: implications for hepatocyte-directed gene transfer. Gene Ther. 2008 Sep; 15(17):1193-9. doi: 10.1038/gt.2008.60 PMID: 18401434
70. Peters RT, Toby G, Lu Q, Liu T, Kulman JD, Low SC, et al. Biochemical and functional characterization of a recombinant monomeric factor VIII-Fc fusion protein. J Thromb Haemost. 2013 Jan; 11(1):132-41. doi: 10.1111/jth.12076 PMID: 23205847
71. Vlot AJ, Koppelman SJ, Meijers JC, Dama C, van den Berg BM, Bouma BN, et al. Kinetics of factor VIII-von Willebrand factor association. Blood. 1996 Mar 1; 87(5):1809-16. PMID: 8634427