1887

Abstract

Hepatitis C virus (HCV) is a major cause of chronic hepatitis and liver carcinoma and new therapies based on novel targets are needed. The tight junction protein claudin 1 (CLDN-1) is essential for HCV cell entry and spread, and anti-CLDN-1 rat and mouse mAbs are safe and effective in preventing and treating HCV infection in a human liver chimeric mouse model. To accelerate translation of these observations into a novel approach to treat HCV infection and disease in humans, we screened a phage display library of human single-chain antibody fragments by using a panel of CLDN-1-positive and -negative cell lines and identified phage specifically binding to CLDN-1. The 12 clones showing the highest levels of binding were converted into human IgG4. Some of these mAbs displayed low-nanomolar affinity, and inhibited infection of human hepatoma Huh7.5 cells by different HCV isolates in a dose-dependent manner. Cross-competition experiments identified six inhibitory mAbs that recognized distinct epitopes. Combination of the human anti-SRB1 mAb C-1671 with these anti-CLDN-1 mAbs could either increase or reduce inhibition of cell culture-derived HCV infection . These novel human anti-CLDN-1 mAbs are potentially useful to develop a new strategy for anti-HCV therapy and lend support to the combined use of antibodies targeting the HCV receptors CLDN-1 and SRB1, but indicate that care must be taken in selecting the proper combination.

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2016-01-01
2020-07-11
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References

  1. Adams G. P., Weiner L. M.. 2005; Monoclonal antibody therapy of cancer. Nat Biotechnol23:1147–1157 [CrossRef][PubMed]
    [Google Scholar]
  2. Ansuini H., Meola A., Gunes Z., Paradisi V., Pezzanera M., Acali S., Santini C., Luzzago A., Mori F., other authors. 2009; Anti-EphA2 antibodies with distinct in vitro properties have equal in vivo efficacy in pancreatic cancer. J Oncol2009:951917 [CrossRef][PubMed]
    [Google Scholar]
  3. Ashfaq U. A., Qasim M., Yousaf M. Z., Awan M. T., Jahan S.. 2011; Inhibition of HCV 3a genotype entry through host CD81 and HCV E2 antibodies. J Transl Med9:194 [CrossRef][PubMed]
    [Google Scholar]
  4. Bartosch B., Vitelli A., Granier C., Goujon C., Dubuisson J., Pascale S., Scarselli E., Cortese R., Nicosia A., Cosset F. L.. 2003; Cell entry of hepatitis C virus requires a set of co-receptors that include the CD81 tetraspanin and the SR-B1 scavenger receptor. J Biol Chem278:41624–41630 [CrossRef][PubMed]
    [Google Scholar]
  5. Brekke O. H., Sandlie I.. 2003; Therapeutic antibodies for human diseases at the dawn of the twenty-first century. Nat Rev Drug Discov2:52–62 [CrossRef][PubMed]
    [Google Scholar]
  6. Catanese M. T., Graziani R., von Hahn T., Moreau M., Huby T., Paonessa G., Santini C., Luzzago A., Rice C. M., other authors. 2007; High-avidity monoclonal antibodies against the human scavenger class B type I receptor efficiently block hepatitis C virus infection in the presence of high-density lipoprotein. J Virol81:8063–8071 [CrossRef][PubMed]
    [Google Scholar]
  7. Chou T. C.. 2006; Theoretical basis, experimental design, and computerized simulation of synergism and antagonism in drug combination studies. Pharmacol Rev58:621–681 [CrossRef][PubMed]
    [Google Scholar]
  8. Chung R. T., Baumert T. F.. 2014; Curing chronic hepatitis C — the arc of a medical triumph. N Engl J Med370:1576–1578 [CrossRef][PubMed]
    [Google Scholar]
  9. Dabbouseh N. M., Jensen D. M.. 2013; Future therapies for chronic hepatitis C. Nat Rev Gastroenterol Hepatol10:268–276 [CrossRef][PubMed]
    [Google Scholar]
  10. Davis G. L., Albright J. E., Cook S. F., Rosenberg D. M.. 2003; Projecting future complications of chronic hepatitis C in the United States. Liver Transpl9:331–338 [CrossRef][PubMed]
    [Google Scholar]
  11. Davis G. L., Nelson D. R., Terrault N., Pruett T. L., Schiano T. D., Fletcher C. V., Sapan C. V., Riser L. N., Li Y., other authors. 2005; A randomized, open-label study to evaluate the safety and pharmacokinetics of human hepatitis C immune globulin (Civacir) in liver transplant recipients. Liver Transpl11:941–949 [CrossRef][PubMed]
    [Google Scholar]
  12. De Lorenzo C., Palmer D. B., Piccoli R., Ritter M. A., D'Alessio G.. 2002; A new human antitumor immunoreagent specific for ErbB2. Clin Cancer Res8:1710–1719[PubMed]
    [Google Scholar]
  13. Dreux M., Pietschmann T., Granier C., Voisset C., Ricard-Blum S., Mangeot P. E., Keck Z., Foung S., Vu-Dac N., other authors. 2006; High density lipoprotein inhibits hepatitis C virus-neutralizing antibodies by stimulating cell entry via activation of the scavenger receptor BI. J Biol Chem281:18285–18295 [CrossRef][PubMed]
    [Google Scholar]
  14. Dustin L. B., Rice C. M.. 2007; Flying under the radar: the immunobiology of hepatitis C. Annu Rev Immunol25:71–99 [CrossRef][PubMed]
    [Google Scholar]
  15. Evans M. J., von Hahn T., Tscherne D. M., Syder A. J., Panis M., Wölk B., Hatziioannou T., McKeating J. A., Bieniasz P. D., Rice C. M.. 2007; Claudin-1 is a hepatitis C virus co-receptor required for a late step in entry. Nature446:801–805 [CrossRef][PubMed]
    [Google Scholar]
  16. Fofana I., Krieger S. E., Grunert F., Glauben S., Xiao F., Fafi-Kremer S., Soulier E., Royer C., Thumann C., other authors. 2010; Monoclonal anti-claudin 1 antibodies prevent hepatitis C virus infection of primary human hepatocytes. Gastroenterology139:953–964, e1–e4 [CrossRef][PubMed]
    [Google Scholar]
  17. Fuh G.. 2007; Synthetic antibodies as therapeutics. Expert Opin Biol Ther7:73–87 [CrossRef][PubMed]
    [Google Scholar]
  18. Fukasawa M., Nagase S., Shirasago Y., Iida M., Yamashita M., Endo K., Yagi K., Suzuki T., Wakita T., other authors. 2015; Monoclonal antibodies against extracellular domains of claudin-1 block hepatitis C virus infection in a mouse model. J Virol89:4866–4879 [CrossRef][PubMed]
    [Google Scholar]
  19. Getts D. R., Getts M. T., McCarthy D. P., Chastain E. M., Miller S. D.. 2010; Have we overestimated the benefit of human(ized) antibodies?. MAbs2:682–694 [CrossRef][PubMed]
    [Google Scholar]
  20. Gottwein J. M., Scheel T. K., Jensen T. B., Lademann J. B., Prentoe J. C., Knudsen M. L., Hoegh A. M., Bukh J.. 2009; Development and characterization of hepatitis C virus genotype 1-7 cell culture systems: role of CD81 and scavenger receptor class B type I and effect of antiviral drugs. Hepatology49:364–377 [CrossRef][PubMed]
    [Google Scholar]
  21. Haid S., Grethe C., Dill M. T., Heim M., Kaderali L., Pietschmann T.. 2014; Isolate-dependent use of claudins for cell entry by hepatitis C virus. Hepatology59:24–34 [CrossRef][PubMed]
    [Google Scholar]
  22. Harris H. J., Davis C., Mullins J. G., Hu K., Goodall M., Farquhar M. J., Mee C. J., McCaffrey K., Young S., other authors. 2010; Claudin association with CD81 defines hepatitis C virus entry. J Biol Chem285:21092–21102 [CrossRef][PubMed]
    [Google Scholar]
  23. Imai K., Takaoka A.. 2006; Comparing antibody and small-molecule therapies for cancer. Nat Rev Cancer6:714–727 [CrossRef][PubMed]
    [Google Scholar]
  24. Khalaj-Kondori M., Sadeghizadeh M., Behmanesh M., Saggio I., Monaci P.. 2011; Chemical coupling as a potent strategy for preparation of targeted bacteriophage-derived gene nanocarriers into eukaryotic cells. J Gene Med13:622–631 [CrossRef][PubMed]
    [Google Scholar]
  25. Kwo P. Y., Badshah M. B.. 2015; New hepatitis C virus therapies: drug classes and metabolism, drug interactions relevant in the transplant settings, drug options in decompensated cirrhosis, and drug options in end-stage renal disease. Curr Opin Organ Transplant20:235–241 [CrossRef][PubMed]
    [Google Scholar]
  26. Lacek K., Urbanowicz R. A., Troise F., De Lorenzo C., Severino V., Di Maro A., Tarr A. W., Ferrara F., Ploss A., other authors. 2014; Dramatic potentiation of the antiviral activity of HIV antibodies by cholesterol conjugation. J Biol Chem289:35015–35028 [CrossRef][PubMed]
    [Google Scholar]
  27. Laemmli U. K.. 1970; Cleavage of structural proteins during the assembly of the head of bacteriophage T4. Nature227:680–685 [CrossRef][PubMed]
    [Google Scholar]
  28. Liang T. J., Ghany M. G.. 2013; Current and future therapies for hepatitis C virus infection. N Engl J Med368:1907–1917 [CrossRef][PubMed]
    [Google Scholar]
  29. Lindenbach B. D., Evans M. J., Syder A. J., Wölk B., Tellinghuisen T. L., Liu C. C., Maruyama T., Hynes R. O., Burton D. R., other authors. 2005; Complete replication of hepatitis C virus in cell culture. Science309:623–626 [CrossRef][PubMed]
    [Google Scholar]
  30. Mailly L., Xiao F., Lupberger J., Wilson G. K., Aubert P., Duong F. H., Calabrese D., Leboeuf C., Fofana I., other authors. 2015; Clearance of persistent hepatitis C virus infection in humanized mice using a claudin-1-targeting monoclonal antibody. Nat Biotechnol33:549–554 [CrossRef][PubMed]
    [Google Scholar]
  31. Manns M. P., Foster G. R., Rockstroh J. K., Zeuzem S., Zoulim F., Houghton M.. 2007; The way forward in HCV treatment – finding the right path. Nat Rev Drug Discov6:991–1000 [CrossRef][PubMed]
    [Google Scholar]
  32. Meuleman P., Catanese M. T., Verhoye L., Desombere I., Farhoudi A., Jones C. T., Sheahan T., Grzyb K., Cortese R., other authors. 2012; A human monoclonal antibody targeting scavenger receptor class B type I precludes hepatitis C virus infection and viral spread in vitro and in vivo. Hepatology55:364–372 [CrossRef][PubMed]
    [Google Scholar]
  33. Neumann A. U., Lam N. P., Dahari H., Gretch D. R., Wiley T. E., Layden T. J., Perelson A. S.. 1998; Hepatitis C viral dynamics in vivo and the antiviral efficacy of interferon-α therapy. Science282:103–107 [CrossRef][PubMed]
    [Google Scholar]
  34. Palmer D. B., Crompton T., Marandi M. B., George A. J., Ritter M. A.. 1999; Intrathymic function of the human cortical epithelial cell surface antigen gp200-MR6: single-chain antibodies to evolutionarily conserved determinants disrupt mouse thymus development. Immunology96:236–245 [CrossRef][PubMed]
    [Google Scholar]
  35. Pawlotsky J. M.. 2011; Treatment failure and resistance with direct-acting antiviral drugs against hepatitis C virus. Hepatology53:1742–1751 [CrossRef][PubMed]
    [Google Scholar]
  36. Pawlotsky J. M., Feld J. J., Zeuzem S., Hoofnagle J. H.. 2015; From non-A, non-B hepatitis to hepatitis C virus cure. J Hepatol62:S87–S99 [CrossRef][PubMed]
    [Google Scholar]
  37. Ploss A., Evans M. J., Gaysinskaya V. A., Panis M., You H., de Jong Y. P., Rice C. M.. 2009; Human occludin is a hepatitis C virus entry factor required for infection of mouse cells. Nature457:882–886 [CrossRef][PubMed]
    [Google Scholar]
  38. Sambrook J., Fritsch E. F., Maniatis T.. 1989; Molecular Cloning: a Laboratory Manual, 2nd edn. Cold Spring Harbor; NY: Cold Spring Harbor Laboratory:
    [Google Scholar]
  39. Sasso E., Paciello R., D'Auria F., Riccio G., Froechlich G., Cortese R., Nicosia A., De Lorenzo C., Zambrano N.. 2015; One-Step Recovery of scFv Clones from High-Throughput Sequencing-Based Screening of Phage Display Libraries Challenged to Cells Expressing Native Claudin-1. Biomed Res Int 2015, 70321
    [Google Scholar]
  40. Scarselli E., Ansuini H., Cerino R., Roccasecca R. M., Acali S., Filocamo G., Traboni C., Nicosia A., Cortese R., Vitelli A.. 2002; The human scavenger receptor class B type I is a novel candidate receptor for the hepatitis C virus. EMBO J21:5017–5025 [CrossRef][PubMed]
    [Google Scholar]
  41. Schiano T. D., Charlton M., Younossi Z., Galun E., Pruett T., Tur-Kaspa R., Eren R., Dagan S., Graham N., other authors. 2006; Monoclonal antibody HCV-AbXTL68 in patients undergoing liver transplantation for HCV: results of a phase 2 randomized study. Liver Transpl12:1381–1389 [CrossRef][PubMed]
    [Google Scholar]
  42. Tellinghuisen T. L., Foss K. L., Treadaway J.. 2008; Regulation of hepatitis C virion production via phosphorylation of the NS5A protein. PLoS Pathog4:e1000032 [CrossRef][PubMed]
    [Google Scholar]
  43. Vidarsson G., Dekkers G., Rispens T.. 2014; IgG subclasses and allotypes: from structure to effector functions. Front Immunol5:520 [CrossRef][PubMed]
    [Google Scholar]
  44. Voisset C., Op de Beeck A., Horellou P., Dreux M., Gustot T., Duverlie G., Cosset F. L., Vu-Dac N., Dubuisson J.. 2006; High-density lipoproteins reduce the neutralizing effect of hepatitis C virus (HCV)-infected patient antibodies by promoting HCV entry. J Gen Virol87:2577–2581 [CrossRef][PubMed]
    [Google Scholar]
  45. Wedemeyer H., Dore G. J., Ward J. W.. 2015; Estimates on HCV disease burden worldwide – filling the gaps. J Viral Hepat22:(Suppl. 1)1–5 [CrossRef][PubMed]
    [Google Scholar]
  46. Welsch C., Domingues F. S., Susser S., Antes I., Hartmann C., Mayr G., Schlicker A., Sarrazin C., Albrecht M., other authors. 2008; Molecular basis of telaprevir resistance due to V36 and T54 mutations in the NS3-4A protease of the hepatitis C virus. Genome Biol9:R16 [CrossRef][PubMed]
    [Google Scholar]
  47. Xiao F., Fofana I., Thumann C., Mailly L., Alles R., Robinet E., Meyer N., Schaeffer M., Habersetzer F., other authors. 2015; Synergy of entry inhibitors with direct-acting antivirals uncovers novel combinations for prevention and treatment of hepatitis C. Gut64:483–494 [CrossRef][PubMed]
    [Google Scholar]
  48. Yamashita M., Iida M., Tada M., Shirasago Y., Fukasawa M., Nagase S., Watari A., Ishii-Watabe A., Yagi K., Kondoh M.. 2015; Discovery of anti-claudin-1 antibodies as candidate therapeutics against hepatitis C virus. J Pharmacol Exp Ther353:112–118 [CrossRef][PubMed]
    [Google Scholar]
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