4,145
Views
24
CrossRef citations to date
0
Altmetric
Report

Structure and characterization of a high affinity C5a monoclonal antibody that blocks binding to C5aR1 and C5aR2 receptors

, , , , , , , , , , , , , , , , , , , , & show all
Pages 104-117 | Received 14 Aug 2017, Accepted 22 Sep 2017, Published online: 24 Oct 2017

References

  • Ricklin D, Hajishengallis G, Yang K, Lambris JD. Complement: a key system for immune surveillance and homeostasis. Nat Immunol. 2010;11(9):785–97. doi:10.1038/ni.1923. PMID:20720586
  • Ehrengruber MU, Geiser T, Deranleau DA. Activation of human neutrophils by C3a and C5A. Comparison of the effects on shape changes, chemotaxis, secretion, and respiratory burst. FEBS Lett. 1994;346(2-3):181–4. doi:10.1016/0014-5793(94)00463-3. PMID:8013630
  • Ali H. Regulation of human mast cell and basophil function by anaphylatoxins C3a and C5a. Immunol Lett. 2010;128(1):36–45. doi:10.1016/j.imlet.2009.10.007. PMID:19895849
  • Cavaillon JM, Fitting C, Haeffner-Cavaillon N. Recombinant C5a enhances interleukin 1 and tumor necrosis factor release by lipopolysaccharide-stimulated monocytes and macrophages. Eur J Immunol. 1990;20(2):253–7. doi:10.1002/eji.1830200204. PMID:1690130
  • Ward PA, Newman LJ. A neutrophil chemotactic factor from human C'5. J Immunol. 1969;102(1):93–9. PMID:5765461
  • DiScipio RG, Schraufstatter IU. The role of the complement anaphylatoxins in the recruitment of eosinophils. Int Immunopharmacol. 2007;7(14):1909–23. doi:10.1016/j.intimp.2007.07.006. PMID:18039528
  • Hartmann K, Henz BM, Krüger-Krasagakes S, Köhl J, Burger R, Guhl S, Haase I, Lippert U, Zuberbier T. C3a and C5a stimulate chemotaxis of human mast cells. Blood. 1997;89(8):2863–70. PMID:9108406
  • Morgan BP, Walters D, Serna M, Bubeck D. Terminal complexes of the complement system: new structural insights and their relevance to function. Immunol Rev. 2016;274(1):141–51.
  • Müller-Eberhard HJ. The killer molecule of complement. J Invest Dermatol. 1985;85(1 Suppl):47s–52s. doi:10.1111/1523-1747.ep12275445. PMID:3891882
  • Tegla CA, Cudrici C, Patel S, Trippe R 3rd, Rus V, Niculescu F, Rus H. Membrane attack by complement: the assembly and biology of terminal complement complexes. Immunol Res. 2011;51(1):45–60. doi:10.1007/s12026-011-8239-5. PMID:21850539
  • Gerard NP, Gerard C. The chemotactic receptor for human C5a anaphylatoxin. Nature. 1991;349(6310):614–7. doi:10.1038/349614a0. PMID:1847994
  • Monk PN, Scola AM, Madala P, Fairlie DP. Function, structure and therapeutic potential of complement C5a receptors. Br J Pharmacol. 2007;152(4):429–48. doi:10.1038/sj.bjp.0707332. PMID:17603557
  • Matthews KW, Mueller-Ortiz SL, Wetsel RA. Carboxypeptidase N: a pleiotropic regulator of inflammation. Mol Immunol. 2004;40(11):785–93. doi:10.1016/j.molimm.2003.10.002. PMID:14687935
  • Fernandez HN, Hugli TE. Primary structural analysis of the polypeptide portion of human C5a anaphylatoxin. Polypeptide sequence determination and assignment of the oligosaccharide attachment site in C5a. J Biol Chem. 1978;253(19):6955–64. PMID:690134
  • Fernandez HN, Henson PM, Otani A, Hugli TE. Chemotactic response to human C3a and C5a anaphylatoxins. I. Evaluation of C3a and C5a leukotaxis in vitro and under stimulated in vivo conditions. J Immunol. 1978;120(1):109–15. PMID:342601
  • Ohno M, Hirata T, Enomoto M, Araki T, Ishimaru H, Takahashi TA. A putative chemoattractant receptor, C5L2, is expressed in granulocyte and immature dendritic cells, but not in mature dendritic cells. Mol Immunol. 2000;37(8):407–12. doi:10.1016/S0161-5890(00)00067-5. PMID:11090875
  • Bamberg CE, Mackay CR, Lee H, Zahra D, Jackson J, Lim YS, Whitfeld PL, Craig S, Corsini E, Lu B, Gerard C, Gerard NP. The C5a receptor (C5aR) C5L2 is a modulator of C5aR-mediated signal transduction. J Biol Chem. 2010;285(10):7633–44. doi:10.1074/jbc.M109.092106. PMID:20044484
  • Croker DE, Halai R, Kaeslin G, Wende E, Fehlhaber B, Klos A, Monk PN, Cooper MA. C5aR2 can modulate ERK1/2 signaling in macrophages via heteromer formation with C5aR1 and beta-arrestin recruitment. Immunol Cell Biol. 2014;92(7):631–9. doi:10.1038/icb.2014.32. PMID:24777312
  • Wang R, Lu B, Gerard C, Gerard NP. Disruption of the complement anaphylatoxin receptor C5L2 exacerbates inflammation in allergic contact dermatitis. J Immunol. 2013;191(8):4001–9. doi:10.4049/jimmunol.1301626. PMID:24043888
  • Gerard NP, Lu B, Liu P, Craig S, Fujiwara Y, Okinaga S, Gerard C. An anti-inflammatory function for the complement anaphylatoxin C5a-binding protein, C5L2. J Biol Chem. 2005;280(48):39677–80. doi:10.1074/jbc.C500287200. PMID:16204243
  • Zhang X, Schmudde I, Laumonnier Y, Pandey MK, Clark JR, König P, Gerard NP, Gerard C, Wills-Karp M, Köhl J. A critical role for C5L2 in the pathogenesis of experimental allergic asthma. J Immunol. 2010;185(11):6741–52. doi:10.4049/jimmunol.1000892. PMID:20974988
  • Xiao H, Dairaghi DJ, Powers JP, Ertl LS, Baumgart T, Wang Y, Seitz LC, Penfold ME, Gan L, Hu P, et al. C5a receptor (CD88) blockade protects against MPO-ANCA GN. J Am Soc Nephrol. 2014;25(2):225–31. doi:10.1681/ASN.2013020143. PMID:24179165
  • Hsu WC, Yang FC, Lin CH, Hsieh SL, Chen NJ. C5L2 is required for C5a-triggered receptor internalization and ERK signaling. Cell Signal. 2014;26(7):1409–19. doi:10.1016/j.cellsig.2014.02.021. PMID:24631530
  • Chen NJ, Mirtsos C, Suh D, Lu YC, Lin WJ, McKerlie C, Lee T, Baribault H, Tian H, Yeh WC. C5L2 is critical for the biological activities of the anaphylatoxins C5a and C3a. Nature. 2007;446(7132):203–7. doi:10.1038/nature05559. PMID:17322907
  • Bosmann M, Grailer JJ, Ruemmler R, Russkamp NF, Zetoune FS, Sarma JV, Standiford TJ, Ward PA. Extracellular histones are essential effectors of C5aR- and C5L2-mediated tissue damage and inflammation in acute lung injury. FASEB J. 2013;27(12):5010–21. doi:10.1096/fj.13-236380. PMID:23982144
  • Rittirsch D, Flierl MA, Nadeau BA, Day DE, Huber-Lang M, Mackay CR, Zetoune FS, Gerard NP, Cianflone K, Köhl J, et al. Functional roles for C5a receptors in sepsis. Nat Med. 2008;14(5):551–7. doi:10.1038/nm1753. PMID:18454156
  • Poppelaars F, van Werkhoven MB, Kotimaa J, Veldhuis ZJ, Ausema A, Broeren SGM, Damman J, Hempel JC, Leuvenink HGD, Daha MR et al. Critical role for complement receptor C5aR2 in the pathogenesis of renal ischemia-reperfusion injury. FASEB J. 2017;31(7):3193–3204. doi:10.1096/fj.201601218R. PMID:28396344
  • Cain SA, Monk PN. The orphan receptor C5L2 has high affinity binding sites for complement fragments C5a and C5a des-Arg(74). J Biol Chem. 2002;277(9):7165–9. doi:10.1074/jbc.C100714200. PMID:11773063
  • Zuiderweg ER, Nettesheim DG, Mollison KW, Carter GW. Tertiary structure of human complement component C5a in solution from nuclear magnetic resonance data. Biochemistry. 1989;28(1):172–85. doi:10.1021/bi00427a025. PMID:2784981
  • Zhang X, Boyar W, Toth MJ, Wennogle L, Gonnella NC. Structural definition of the C5a C terminus by two-dimensional nuclear magnetic resonance spectroscopy. Proteins. 1997;28(2):261–7. doi:10.1002/(SICI)1097-0134(199706)28:2%3c261::AID-PROT13%3e3.0.CO;2-G. PMID:9188742
  • Huber-Lang MS, Sarma JV, McGuire SR, Lu KT, Padgaonkar VA, Younkin EM, Guo RF, Weber CH, Zuiderweg ER, Zetoune FS. Structure-function relationships of human C5a and C5aR. J Immunol. 2003;170(12):6115–24. doi:10.4049/jimmunol.170.12.6115. PMID:12794141
  • Vijayan S, Asare Y, Grommes J, Soehnlein O, Lutgens E, Shagdarsuren G, Togtokh A, Jacobs MJ, Fischer JW, Bernhagen J et al. High expression of C5L2 correlates with high proinflammatory cytokine expression in advanced human atherosclerotic plaques. Am J Pathol. 2014;184(7):2123–33. doi:10.1016/j.ajpath.2014.04.004. PMID:24819959
  • Hao J, Wang C, Yuan J, Chen M, Zhao MH. A pro-inflammatory role of C5L2 in C5a-primed neutrophils for ANCA-induced activation. PLoS One. 2013;8(6):e66305. doi:10.1371/journal.pone.0066305. PMID:23785491
  • Rother RP, Rollins SA, Mojcik CF, Brodsky RA, Bell L. Discovery and development of the complement inhibitor eculizumab for the treatment of paroxysmal nocturnal hemoglobinuria. Nat Biotechnol. 2007;25(11):1256–64. doi:10.1038/nbt1344. PMID:17989688
  • Drogari-Apiranthitou M, Kuijper EJ, Dekker N, Dankert J. Complement activation and formation of the membrane attack complex on serogroup B Neisseria meningitidis in the presence or absence of serum bactericidal activity. Infect Immun. 2002;70(7):3752–8. doi:10.1128/IAI.70.7.3752-3758.2002. PMID:12065518
  • Riedemann NC, Habel M, Ziereisen J, Hermann M, Schneider C, Wehling C, Kirschfink M, Kentouche K, Guo R. Controlling the anaphylatoxin C5a in diseases requires a specifically targeted inhibition. Clin Immunol. 2017;180:25–32. doi:10.1016/j.clim.2017.03.012. PMID:28366510
  • Nandakumar KS, Jansson A, Xu B, Rydell N, Ahooghalandari P, Hellman L, Blom AM, Holmdahl R. A recombinant vaccine effectively induces c5a-specific neutralizing antibodies and prevents arthritis. PLoS One. 2010;5(10):e13511. doi:10.1371/journal.pone.0013511. PMID:20975959
  • Landlinger C, Oberleitner L, Gruber P, Noiges B, Yatsyk K, Santic R, Mandler M, Staffler G. Active immunization against complement factor C5a: a new therapeutic approach for Alzheimer's disease. J Neuroinflammation. 2015;12:150. doi:10.1186/s12974-015-0369-6. PMID:26275910
  • Vaughan TJ, Williams AJ, Pritchard K, Osbourn JK, Pope AR, Earnshaw JC, McCafferty J, Hodits RA, Wilton J, Johnson KS. Human antibodies with sub-nanomolar affinities isolated from a large non-immunized phage display library. Nat Biotechnol. 1996;14(3):309–14. doi:10.1038/nbt0396-309. PMID:9630891
  • Groves M, Lane S, Douthwaite J, Lowne D, Rees DG, Edwards B, Jackson RH. Affinity maturation of phage display antibody populations using ribosome display. J Immunol Methods. 2006;313(1-2):129–39. doi:10.1016/j.jim.2006.04.002. PMID:16730741
  • Lloyd C, Lowe D, Edwards B, Welsh F, Dilks T, Hardman C, Vaughan T. Modelling the human immune response: performance of a 1011 human antibody repertoire against a broad panel of therapeutically relevant antigens. Protein Eng Des Sel. 2009;22(3):159–68. doi:10.1093/protein/gzn058. PMID:18974080
  • Angal S, King DJ, Bodmer MW, Turner A, Lawson AD, Roberts G, Pedley B, Adair JR. A single amino acid substitution abolishes the heterogeneity of chimeric mouse/human (IgG4) antibody. Mol Immunol. 1993;30(1):105–8. doi:10.1016/0161-5890(93)90432-B. PMID:8417368
  • Jefferis R. Antibody therapeutics: isotype and glycoform selection. Expert Opin Biol Ther. 2007;7(9):1401–13. doi:10.1517/14712598.7.9.1401. PMID:17727329
  • Kabat EA, Wu TT, Perry HM, Gottesman KS, Foeller C. Sequences of proteins of immunological interest. 5th Edition, US Department of Health and Human Services. Bethesda (MD): National Institutes for Health publication. 91--3242. 1991 p. 662,680,689.
  • Fung M, Lu M, Fure H, Sun W, Sun C, Shi NY, Dou Y, Su J, Swanson X, Mollnes TE. Pre-neutralization of C5a-mediated effects by the monoclonal antibody 137-26 reacting with the C5a moiety of native C5 without preventing C5 cleavage. Clin Exp Immunol. 2003;133(2):160–9. doi:10.1046/j.1365-2249.2003.02213.x. PMID:12869020
  • Mollnes TE, Brekke OL, Fung M, Fure H, Christiansen D, Bergseth G, Videm V, Lappegård KT, Köhl J, Lambris JD. Essential role of the C5a receptor in E coli-induced oxidative burst and phagocytosis revealed by a novel lepirudin-based human whole blood model of inflammation. Blood. 2002;100(5):1869–77. PMID:12176911
  • Underhill DM, Ozinsky A. Phagocytosis of microbes: complexity in action. Annu Rev Immunol. 2002;20:825–52. doi:10.1146/annurev.immunol.20.103001.114744. PMID:11861619
  • Williamson MP, Madison VS. Three-dimensional structure of porcine C5adesArg from 1H nuclear magnetic resonance data. Biochemistry. 1990;29(12):2895–905. doi:10.1021/bi00464a002. PMID:2337573
  • Schatz-Jakobsen JA, Yatime L, Larsen C, Petersen SV, Klos A, Andersen GR. Structural and functional characterization of human and murine C5a anaphylatoxins. Acta Crystallogr D Biol Crystallogr. 2014;70(Pt 6):1704–17. doi:10.1107/S139900471400844X. PMID:24914981
  • Foote J, Winter G. Antibody framework residues affecting the conformation of the hypervariable loops. J Mol Biol. 1992;224(2):487–99. doi:10.1016/0022-2836(92)91010-M. PMID:1560463
  • Johnson RJ, Tamerius JD, Chenoweth DE. Identification of an antigenic epitope and receptor binding domain of human C5a. J Immunol. 1987;138(11):3856–62. PMID:2438329
  • Kola A, Baensch M, Bautsch W, Hennecke M, Klos A, Casaretto M, Köhl J. Epitope mapping of a C5a neutralizing mAb using a combined approach of phage display, synthetic peptides and site-directed mutagenesis. Immuno Technol. 1996;2(2):115–26. doi:10.1016/1380-2933(96)00425-3.
  • Guo R, Reidemann NC, Li Y, Shen B, inventors. Inflarx Gmbh, assignee. Anti-C5a binding antibodies with high block activity. United States Patent 8802096. 2014.
  • Fung M, Lu M, Sun WNC, Sun CR, inventors. Genentech Inc., assignee. Anti-C5/C5a antibodies and methods of use. United States Patent 8372404. 2013.
  • Siciliano SJ, Rollins TE, DeMartino J, Konteatis Z, Malkowitz L, Van Riper G, Bondy S, Rosen H, Springer MS. Two-site binding of C5a by its receptor: an alternative binding paradigm for G protein-coupled receptors. Proc Natl Acad Sci U S A. 1994;91(4):1214–8. doi:10.1073/pnas.91.4.1214. PMID:8108389
  • Mollison KW, Mandecki W, Zuiderweg ER, Fayer L, Fey TA, Krause RA, Conway RG, Miller L, Edalji RP, Shallcross MA, et al. Identification of receptor-binding residues in the inflammatory complement protein C5a by site-directed mutagenesis. Proc Natl Acad Sci U S A. 1989;86(1):292–6. doi:10.1073/pnas.86.1.292. PMID:2643101
  • DeMartino JA, Van Riper G, Siciliano SJ, Molineaux CJ, Konteatis ZD, Rosen H, Springer MS. The amino terminus of the human C5a receptor is required for high affinity C5a binding and for receptor activation by C5a but not C5a analogs. J Biol Chem. 1994;269(20):14446–50. PMID:8182049
  • Klos A, Wende E, Wareham KJ, Monk PN. International Union of Basic and Clinical Pharmacology. [corrected]. LXXXVII. Complement peptide C5a, C4a, and C3a receptors. Pharmacol Rev. 2013;65(1):500–43. doi:10.1124/pr.111.005223. PMID:23383423
  • Otto M, Hawlisch H, Monk PN, Müller M, Klos A, Karp CL, Köhl J. C5a mutants are potent antagonists of the C5a receptor (CD88) and of C5L2: position 69 is the locus that determines agonism or antagonism. J Biol Chem. 2004;279(1):142–51. doi:10.1074/jbc.M310078200. PMID:14570896
  • Croker DE, Monk PN, Halai R, Kaeslin G, Schofield Z, Wu MC, Clark RJ, Blaskovich MA, Morikis D, Floudas CA et al. Discovery of functionally selective C5aR2 ligands: novel modulators of C5a signalling. Immunol Cell Biol. 2016;94(8):787–95. doi:10.1038/icb.2016.43. PMID:27108698
  • Scola AM, Higginbottom A, Partridge LJ, Reid RC, Woodruff T, Taylor SM, Fairlie DP, Monk PN. The role of the N-terminal domain of the complement fragment receptor C5L2 in ligand binding. J Biol Chem. 2007;282(6):3664–71. doi:10.1074/jbc.M609178200. PMID:17158873
  • Andersson C, Wenander CS, Usher PA, Hebsgaard JB, Sondergaard BC, Rønø B, Mackay C, Friedrichsen B, Chang C, Tang R et al. Rapid-onset clinical and mechanistic effects of anti-C5aR treatment in the mouse collagen-induced arthritis model. Clin Exp Immunol. 2014;177(1):219–33. doi:10.1111/cei.12338. PMID:24665841
  • Staab EB, Sanderson SD, Wells SM, Poole JA. Treatment with the C5a receptor/CD88 antagonist PMX205 reduces inflammation in a murine model of allergic asthma. Int Immunopharmacol. 2014;21(2):293–300. doi:10.1016/j.intimp.2014.05.008. PMID:24859057
  • Rawal N, Pangburn MK. Formation of high affinity C5 convertase of the classical pathway of complement. J Biol Chem. 2003;278(40):38476–83. doi:10.1074/jbc.M307017200. PMID:12878586
  • Hillmen P, Muus P, Röth A, Elebute MO, Risitano AM, Schrezenmeier H, Szer J, Browne P, Maciejewski JP, Schubert J et al. Long-term safety and efficacy of sustained eculizumab treatment in patients with paroxysmal nocturnal haemoglobinuria. Br J Haematol. 2013;162(1):62–73. doi:10.1111/bjh.12347. PMID:23617322
  • Gatault P, Brachet G, Ternant D, Degenne D, Récipon G, Barbet C, Gyan E, Gouilleux-Gruart V, Bordes C, Farrell A, et al. Therapeutic drug monitoring of eculizumab: Rationale for an individualized dosing schedule. MAbs. 2015;7(6):1205–11. doi:10.1080/19420862.2015.1086049. PMID:26337866
  • Janatova J. C3, C5 components and C3a, C4a, and C5a fragments of the complement system. Methods Enzymol. 1988;162:579–625. doi:10.1016/0076-6879(88)62104-5. PMID:3265757
  • Hawkins RE, Russell SJ, Winter G. Selection of phage antibodies by binding affinity. Mimicking affinity maturation. J Mol Biol. 1992;226(3):889–96. doi:10.1016/0022-2836(92)90639-2. PMID:1507232
  • Dobson CL, Main S, Newton P, Chodorge M, Cadwallader K, Humphreys R, Albert V, Vaughan TJ, Minter RR, Edwards BM. Human monomeric antibody fragments to TRAIL-R1 and TRAIL-R2 that display potent in vitro agonism. MAbs. 2009;1(6):552–62. doi:10.4161/mabs.1.6.10057. PMID:20068388
  • Thompson J, Pope T, Tung JS, Chan C, Hollis G, Mark G, Johnson KS Affinity maturation of a high-affinity human monoclonal antibody against the third hypervariable loop of human immunodeficiency virus: use of phage display to improve affinity and broaden strain reactivity. J Mol Biol. 1996;256(1):77–88. doi:10.1006/jmbi.1996.0069. PMID:8609615
  • Persic L, Roberts A, Wilton J, Cattaneo A, Bradbury A, Hoogenboom HR. An integrated vector system for the eukaryotic expression of antibodies or their fragments after selection from phage display libraries. Gene. 1997;187(1):1–8. doi:10.1016/S0378-1119(96)00627-010.1016/S0378-1119(96)00628-2. PMID:9073060
  • Choi KH, Gaynor JB, White KG, Lopez C, Bosio CM, Karkhoff-Schweizer RR, Schweizer HP. A Tn7-based broad-range bacterial cloning and expression system. Nat Methods. 2005;2(6):443–8. doi:10.1038/nmeth765. PMID:15908923
  • Paczkowski NJ, Finch AM, Whitmore JB, Short AJ, Wong AK, Monk PN, Cain SA, Fairlie DP, Taylor SM. Pharmacological characterization of antagonists of the C5a receptor. Br J Pharmacol. 1999;128(7):1461–6. doi:10.1038/sj.bjp.0702938. PMID:10602324
  • Leslie AG. The integration of macromolecular diffraction data. Acta Crystallogr D Biol Crystallogr. 2006;62(Pt 1):48–57. doi:10.1107/S0907444905039107. PMID:16369093
  • Battye TG, Kontogiannis L, Johnson O, Powell HR, Leslie AG. iMOSFLM: a new graphical interface for diffraction-image processing with MOSFLM. Acta Crystallogr D Biol Crystallogr. 2011;67(Pt 4):271–81. doi:10.1107/S0907444910048675. PMID:21460445
  • Evans P. Scaling and assessment of data quality. Acta Crystallogr D Biol Crystallogr. 2006;62(Pt 1):72–82. doi:10.1107/S0907444905036693. PMID:16369096
  • Winn MD, Ballard CC, Cowtan KD, Dodson EJ, Emsley P, Evans PR, Keegan RM, Krissinel EB, Leslie AG, McCoy A et al. Overview of the CCP4 suite and current developments. Acta Crystallogr D Biol Crystallogr. 2011;67(Pt 4):235–42. doi:10.1107/S0907444910045749. PMID:21460441
  • McCoy AJ, Grosse-Kunstleve RW, Storoni LC, Read RJ. Likelihood-enhanced fast translation functions. Acta Crystallogr D Biol Crystallogr. 2005;61(Pt 4):458–64. doi:10.1107/S0907444905001617. PMID:15805601
  • Storoni LC, McCoy AJ, Read RJ. Likelihood-enhanced fast rotation functions. Acta Crystallogr D Biol Crystallogr. 2004;60(Pt 3):432–8. doi:10.1107/S0907444903028956. PMID:14993666
  • Emsley P, Lohkamp B, Scott WG, Cowtan K. Features and development of Coot. Acta Crystallogr D Biol Crystallogr. 2010;66(Pt 4):486–501. doi:10.1107/S0907444910007493. PMID:20383002
  • Murshudov GN, Skubák P, Lebedev AA, Pannu NS, Steiner RA, Nicholls RA, Winn MD, Long F, Vagin AA. REFMAC5 for the refinement of macromolecular crystal structures. Acta Crystallogr D Biol Crystallogr. 2011;67(Pt 4):355–67. doi:10.1107/S0907444911001314. PMID:21460454