Journal of Hepatology
Volume 53, Issue 4 , Pages 599-607 , October 2010

A phase I clinical trial of dendritic cell immunotherapy in HCV-infected individuals

  • Eric J. Gowans

      Affiliations

    • Virology Program, Burnet Institute, G.P.O. Box 2284, Melbourne, Vic. 3001, Australia
    • Corresponding Author InformationCorresponding author. Present address: Women’s and Children’s Health Research Institute, 72 King William Road, North Adelaide, SA 5006, Australia. Tel.: +61 8 8161 7443; fax: +61 8 8239 0267.
    • ,
  • Stuart Roberts

      Affiliations

    • Department of Gastroenterology, The Alfred Hospital, Commercial Road, Melbourne, Vic. 3004, Australia
    • ,
  • Kathryn Jones

      Affiliations

    • Virology Program, Burnet Institute, G.P.O. Box 2284, Melbourne, Vic. 3001, Australia
    • ,
  • Irene Dinatale

      Affiliations

    • Department of Microbiology and Immunology, The University of Melbourne, Parkville, Vic. 3010, Australia
    • ,
  • Philippe A. Latour

      Affiliations

    • Virology Program, Burnet Institute, G.P.O. Box 2284, Melbourne, Vic. 3001, Australia
    • ,
  • Brendan Chua

      Affiliations

    • Department of Microbiology and Immunology, The University of Melbourne, Parkville, Vic. 3010, Australia
    • ,
  • Emily M.Y. Eriksson

      Affiliations

    • Department of Microbiology and Immunology, The University of Melbourne, Parkville, Vic. 3010, Australia
    • ,
  • Ruth Chin

      Affiliations

    • Department of Infectious Diseases, Austin Hospital, Heidelberg, Vic., Australia
    • ,
  • Shuo Li

      Affiliations

    • Virology Program, Burnet Institute, G.P.O. Box 2284, Melbourne, Vic. 3001, Australia
    • ,
  • Dominic M. Wall

      Affiliations

    • Centre for Blood Cell Therapies, Peter MacCallum Cancer Centre, St. Andrews Place, East Melbourne, Vic. 3002, Australia
    • ,
  • Rosemary L. Sparrow

      Affiliations

    • Australian Red Cross Blood Service, Kavanagh Street, South Melbourne, Vic. 3205, Australia
    • ,
  • Jude Moloney

      Affiliations

    • Centre for Blood Cell Therapies, Peter MacCallum Cancer Centre, St. Andrews Place, East Melbourne, Vic. 3002, Australia
    • ,
  • Maureen Loudovaris

      Affiliations

    • Centre for Blood Cell Therapies, Peter MacCallum Cancer Centre, St. Andrews Place, East Melbourne, Vic. 3002, Australia
    • ,
  • Rosemary Ffrench

      Affiliations

    • Virology Program, Burnet Institute, G.P.O. Box 2284, Melbourne, Vic. 3001, Australia
    • ,
  • H. Miles Prince

      Affiliations

    • Centre for Blood Cell Therapies, Peter MacCallum Cancer Centre, St. Andrews Place, East Melbourne, Vic. 3002, Australia
    • Faculty of Medicine, Dentistry and Health Sciences, The University of Melbourne, Parkville, Vic. 3052, Australia
    • ,
  • Derek Hart

      Affiliations

    • Mater Medical Research Institute, Aubigny Place, Raymond Terrace, South Brisbane, Qld 4101, Australia
    • ,
  • Weng Zeng

      Affiliations

    • Department of Microbiology and Immunology, The University of Melbourne, Parkville, Vic. 3010, Australia
    • ,
  • Joseph Torresi

      Affiliations

    • Department of Infectious Diseases, Austin Hospital, Heidelberg, Vic., Australia
    • ,
  • Lorena E. Brown

      Affiliations

    • Department of Microbiology and Immunology, The University of Melbourne, Parkville, Vic. 3010, Australia
    • ,
  • David C. Jackson

      Affiliations

    • Department of Microbiology and Immunology, The University of Melbourne, Parkville, Vic. 3010, Australia

Received 28 September 2009 ,Revised 11 May 2010 ,Accepted 30 May 2010.

References 

  1. Bowen D, Walker C. Adaptive immune responses in acute and chronic hepatitis C virus infection. Nature. 2005;436:946–952
  2. Thimme R, Oldach D, Chang KM, Steiger C, Ray SC, Chisari FV. Determinants of viral clearance and persistence during acute hepatitis C virus infections. J Exp Med. 2001;194:1395–1406
  3. Villano SA, Vlahov D, Nelson KE, Cohn S, Thomas DL. Persistence of viremia and the importance of long-term follow up after acute hepatitis C infection. Hepatology. 1999;29:908–914
  4. Gale M, Foy E. Evasion of intracellular host defence by hepatitis C virus. Nature. 2005;436:939–945
  5. Kato N, Ootsuyama Y, Sekiya H, Ohkoshi S, Nakazawa T, Hijikata M, et al. Genetic drift in hypervariable region 1 of the viral genome in persistent hepatitis C virus infection. J Virol. 1994;68:4776–4784
  6. Erickson AL, Kimura Y, Igarashi S, Eichelberger J, Houghton M, Sidney J, et al. The outcome of hepatitis C virus infection is predicted by escapte mutations in epitopes targeted by cytotoxic T lymphocytes. Immunity. 2001;15:883–895
  7. Crotta S, Stilla A, Wack A, D’Andrea A, Nuti S, D’Oro U, et al. Inhibition of natural killer cells through engagement of the CD81 by the major hepatitis C virus envelope protein. J Exp Med. 2002;195:35–41
  8. Tseng CT, Klimpel GR. Binding of the hepatitis C virus E2 to CD81 inhibits natural killer cell function. J Exp Med. 2002;195:43–49
  9. Wedemeyer H, He XS, Nascimbeni M, Davis AR, Greenberg HB, Hoofnagle JH, et al. Impaired effector function of hepatitis C virus-specific CD8+ T cell in chronic hepatitis C virus infection. J Immunol. 2002;169:3447–3458
  10. Gowans EJ, Jones KL, Bharadwaj M, Jackson DC. Prospects for dendritic cell vaccination in persistent infection with hepatitis C virus. J Clin Virol. 2004;30:283–290
  11. Radziewicz H, Ibegbu CC, Fernandez ML, Workowski KA, Obideen K, Wehbi M, et al. Liver-infiltrating lymphocytes in chronic human hepatitis C virus infection display an exhausted phenotype with high levels of PD-1 and low levels of CD127 expression. J Virol. 2007;81:2545–2553
  12. Li S, Jones KL, Woollard DJ, Dromey J, Paukovics G, Plebanski M, et al. Defining target antigens for CD25+FOXP3+IFN-γ− regulatory T cells in chronic hepatitis C virus infection. Immunol Cell Biol. 2007;85:197–204
  13. Donaldson PT. The interrelationship between hepatitis C and HLA. Eur J Clin Invest. 1999;29:280–283
  14. Urbani S, Boni C, Missale G, Elia G, Cavallo C, Massari M, et al. Virus-specific CD8+ lymphocytes share the same effector-memory phenotype but exhibit junctional differences in acute hepatitis B and C. J Virol. 2002;76:12423–12434
  15. Urbani S, Amadei B, Fisicaro P, Tola D, Orlandini A, Sacchelli L, et al. Outcome of acute hepatitis C is related to virus-specific CD4 function and maturation of antiviral memory CD8 responses. Hepatology. 2006;44:126–139
  16. Banchereau J, Steinman RM. Dendritic cells and the control of immunity. Nature. 1998;392:245–252
  17. Randolph GJ, Beaulieu S, Lebecque S, Steinman RM, Muller WA. Differentiation of monocytes into dendritic cells in a model of transendothelial trafficking. Science. 1998;282:480–483
  18. Longman RS, Talal AH, Jacobson IM, Rice CM, Albert ML. Normal functional capacity in circulating myeloid and plasmacytoid dendritic cells in patients with chronic hepatitis C. J Infect Dis. 2005;192:497–503
  19. Piccioli D, Tavarini S, Nuti S, Colombatto P, Brunetto M, Bonino F, et al. Comparable functions of plasmacytoid and monocyte-derived dendritic cells in chronic hepatitis C patients and healthy donors. J Hepatol. 2005;42:61–67
  20. Longman RS, Talal AH, Jacobson IM, Albert ML, Rice CM. Presence of functional dendritic cells in patients chronically infected with hepatitis C. Blood. 2004;103:1026–1029
  21. Chua BY, Healy A, Cameron P, Fowler NL, Brown LE, Zeng W, et al. Maturation of dendritic cells with lipopeptides that represent vaccine candidates for hepatitis C virus. Immunol Cell Biol. 2003;81:67–72
  22. Jackson DC, Deliyannis G, Eriksson E, Dinatale I, Rizkalla M, Gowans EJ. Dendritic cell immunotherapy of hepatitis C virus infection: toxicology of lipopeptide-loaded dendritic cells. Int J Peptide Res Ther. 2005;11:1–12
  23. Jones KL, Brown LE, Eriksson EMY, Ffrench RA, Latour PA, Loveland BE, et al. Human dendritic cells pulsed with specific lipopeptides stimulate autologous antigen-specific CD8+ T-cells without the addition of exogenous maturation factors. J Viral Hepat. 2008;15:761–772
  24. Zeng W, Ghosh S, Lau YF, Brown LE, Jackson DC. Highly immunogenic and totally synthetic lipopeptides as self-adjuvanting immunocontraceptive vaccines. J Immunol. 2002;169:4905–4912
  25. Trowbridge R, Sloots TP, Buda P, Faoagali J, Hyland C, Young I, et al. An ELISA for the detection of antibody to the core antigen of hepatitis C virus: use in diagnosis and analysis of indeterminate samples. J Hepatol. 1996;24:532–538
  26. Larsson M, Babcock E, Grakoui A, Shoukry N, Lauer G, Rice C, et al. Lack of phenotypic and functional impairment in dendritic cells from chimpanzees chronically infected with hepatitis C virus. J Virol. 2004;78:6151–6161
  27. Racanelli V, Behrens SE, Aliberti J, Rehermann B. Dendritic cells transfected with cytopathic self-replicating RNA induce crosspriming of CD8+ T cells and antiviral immunity. Immunity. 2004;20:47–58
  28. Yu H, Huang H, Xiang J, Babiuk LA, van Drunen Littel-van den Hurk S. Dendritic cells pulsed with hepatitis C virus NS3 protein induce immune responses and protection from infection with recombinant vaccinia virus expressing NS3. J Gen Virol. 2006;87:1–10
  29. Kuzushita N, Gregory SH, Monti NA, Carlson R, Gehring S, Wands JR. Vaccination with protein-transduced dendritic cells elicits a sustained response to hepatitis C viral antigens. Gastroenterology. 2006;130:453–464
  30. Encke J, Findeklee J, Geib J, Pfaff E, Stremmel W. Prophylactic and therapeutic vaccination with dendritic cells against hepatitis C virus infection. Clin Exp Immunol. 2005;142:362–369
  31. Brown LE, Jackson DC. Lipid-based self-adjuvanting vaccines. Curr Drug Deliv. 2005;2:383–393
  32. Prince HM, Wall DM, Ritchie D, Honemann D, Harrison S, Quach H, et al. In vivo tracking of dendritic cells in patients with multiple myeloma. J Immunother. 2008;31:166–179
  33. Tjoa BA, Simmons SJ, Bowes VA, Ragde H, Rogers M, Elgamal A, et al. Evaluation of phase I/II clinical trials in prostate cancer with dendritic cells and PSMA peptides. Prostate. 1998;36:39–44
  34. Smithers M, O’Connell K, MacFadyen S, Chambers M, Greenwood K, Boyce A, et al. Clinical response after intradermal immature dendritic cell vaccination in metastatic melanoma is associated with immune response to particulate antigen. Cancer Immunol Immunother. 2003;52:41–52
  35. Schiff ER, Everson GT, Tsai N, Bzowej NH, Gish RG, McHutchison JG, et al. HCV-specific cellular immunity, RNA reductions, and normalization of ALT in chronic HCV subjects after treatment with GI-5005, a yeast-based immunotherapy targeting NS3 and core: a randomized, double-blind, placebo controlled Phase 1B study. Hepatology. 2007;44:(Abs #LB17)
  36. Nevens F, Roskams T, Van Vlierberghe H, Horsmans Y, Sprengers D, Elewaut A, et al. A pilot study of therapeutic vaccination with envelope protein E1 in 35 patients with chronic hepatitis C. Hepatology. 2003;38:1289–1296
  37. Alvarez-Lajonchere L, Shoukry NH, Amador-Canizares Y, Gra B, Helle F, Bedard N, et al. Immunogenicity of CIGB-230, a therapeutic DNA vaccine preparation, in HCV-chronically infected individuals in a Phase I clinical trial. J Viral Hepat. 2009;16:156–167
  38. Klade CS, Wedemeyer H, Berg T, Hinrichsen H, Cholewinska G, Zeuzem S, et al. Therapeutic vaccination of chronic hepatitis C nonresponder patients with the peptide vaccine IC41. Gastroenterology. 2008;134:1385–1395
  39. Yutani S, Yamada A, Yoshida K, Takao Y, Tamura M, Komatsu N, et al. Phase 1 clinical study of a personalized peptide vaccination for patients infected with hepatitis C virus (HCV) 1b who failed to respond to interferon-based therapy. Vaccine. 2007;25:7429–7435
  40. Lawitz E, Rodriguez-Torres M, Muir AJ, Kieffer TL, McNair L, Khunvichai A, et al. Antiviral effects and safety of telaprevir, peginterferon alfa-2a, and ribavirin for 28 days in hepatitis C patients. J Hepatol. 2008;49:163–169
  41. Vulink A, Radford K, Melief C, Hart D. Dendritic cells in cancer immunotherapy. Adv Cancer Res. 2008;99:363–407

PII: S0168-8278(10)00550-7

doi: 10.1016/j.jhep.2010.05.007

Journal of Hepatology
Volume 53, Issue 4 , Pages 599-607 , October 2010

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