Transfusionsmedizin 2014; 4(3): 143-152
DOI: 10.1055/s-0033-1357968
CME-Fortbildung
Georg Thieme Verlag KG Stuttgart · New York

Adoptive Immuntherapie mit dendritischen Zellen

H. Hackstein
Further Information

Publication History

Publication Date:
18 August 2014 (online)

Zusammenfassung

Dendritische Zellen sind professionelle antigenpräsentierende Zellen und spielen eine Schlüsselrolle bei der Induktion und Regulation von Immunantworten. Dendritische Zellen induzieren nicht nur erworbene Immunantworten über die Aktivierung von naiven T- und B-Lymphozyten, sondern kontrollieren Immunität über die Aktivierung von antigenspezifischen T-Regulatorzellen und die Eliminierung von T-Zellen. Bezugnehmend auf ihre Schlüsselrolle im Immunsystem wurden klinische Vakzinierungsstrategien mit dendritischen Zellen in den letzten Jahren kontinuierlich weiterentwickelt und verbessert. In dieser Arbeit werden die wesentlichen Entwicklungen der adoptiven Immuntherapie mit dendritischen Zellen zusammengefasst, welche den klinischen Einsatz voraussichtlich prägen werden.

 
  • Literatur

  • 1 Steinman RM. Decisions about dendritic cells: past, present, and future. Annu Rev Immunol 2012; 30: 1-22
  • 2 Steinman RM, Cohn ZA. Identification of a novel cell type in peripheral lymphoid organs of mice. I. Morphology, quantitation, tissue distribution. J Exp Med 1973; 137: 1142-1162
  • 3 Vacchelli E, Vitale I, Eggermont A et al. Trial watch: Dendritic cell-based interventions for cancer therapy. Oncoimmunology 2013; 2: e25771
  • 4 Volchenkov R, Sprater F, Vogelsang P et al. The 2011 Nobel Prize in physiology or medicine. Scand J Immunol 2012; 75: 1-4
  • 5 Banchereau J, Briere F, Caux C et al. Immunobiology of dendritic cells. Annu Rev Immunol 2000; 18: 767-811
  • 6 Steinman R. Dendritic cells: understanding immunogenicity. Eur J Immunol 2007; 37 (Suppl. 01) S53-S60
  • 7 Steinman R, Banchereau J. Taking dendritic cells into medicine. Nature 2007; 449: 419-426
  • 8 Haniffa M, Collin M, Ginhoux F. Ontogeny and functional specialization of dendritic cells in human and mouse. Adv Immunol 2013; 120: 1-49
  • 9 Kushwah R, Hu J. Complexity of dendritic cell subsets and their function in the host immune system. Immunology 2011; 133: 409-419
  • 10 Rosborough BR, Raich-Regue D, Matta BM et al. Murine dendritic cell rapamycin-resistant and rictor-independent mTOR controls IL-10, B7-H1 and regulatory T cell induction. Blood 2013; 121: 3619-3630
  • 11 Hackstein H, Morelli AE, Larregina AT et al. Aspirin inhibits in vitro maturation and in vivo immunostimulatory function of murine myeloid dendritic cells. J Immunol 2001; 166: 7053-7062
  • 12 Hackstein H, Thomson A. Dendritic cells: emerging pharmacological targets of immunosuppressive drugs. Nat Rev Immunol 2004; 4: 24-34
  • 13 Steinschulte C, Taner T, Thomson AW et al. Cutting edge: sanglifehrin A, a novel cyclophilin-binding immunosuppressant blocks bioactive IL-12 production by human dendritic cells. J Immunol 2003; 171: 542-546
  • 14 Hackstein H, Steinschulte C, Fiedel S et al. Sanglifehrin a blocks key dendritic cell functions in vivo and promotes long-term allograft survival together with low-dose CsA. Am J Transplant 2007; 7: 789-798
  • 15 Taner T, Hackstein H, Wang Z et al. Rapamycin-treated, alloantigen-pulsed host dendritic cells induce ag-specific T cell regulation and prolong graft survival. Am J Transplant 2005; 5: 228-236
  • 16 Probst HC, Muth S, Schild H. Regulation of the tolerogenic function of steady-state DCs. Eur J Immunol 2014; 44: 927-933
  • 17 Merad M, Sathe P, Helft J et al. The dendritic cell lineage: ontogeny and function of dendritic cells and their subsets in the steady state and the inflamed setting. Annu Rev Immunol 2013; 31: 563-604
  • 18 Kalinski P. Dendritic cells in immunotherapy of established cancer: Roles of signals 1, 2, 3 and 4. Curr Opin Investig Drugs 2009; 10: 526-535
  • 19 Kalinski P, Okada H. Polarized dendritic cells as cancer vaccines: directing effector-type T cells to tumors. Semin Immunol 2010; 22: 173-182
  • 20 Kalinski P, Muthuswamy R, Urban J. Dendritic cells in cancer immunotherapy: vaccines and combination immunotherapies. Expert Rev Vaccines 2013; 12: 285-295
  • 21 Kalinski P, Okada H. Polarized dendritic cells as cancer vaccines: directing effector-type T cells to tumors. Semin Immunol 2010; 22: 173-182
  • 22 Merad M, Sathe P, Helft J et al. The dendritic cell lineage: ontogeny and function of dendritic cells and their subsets in the steady state and the inflamed setting. Annu Rev Immunol 2013; 31: 563-604
  • 23 Collin M, McGovern N, Haniffa M. Human dendritic cell subsets. Immunology 2013; 140: 22-30
  • 24 Ziegler-Heitbrock L, Ancuta P, Crowe S et al. Nomenclature of monocytes and dendritic cells in blood. Blood 2010; 116: e74-80
  • 25 Dzionek A, Fuchs A, Schmidt P et al. BDCA-2, BDCA-3, and BDCA-4: three markers for distinct subsets of dendritic cells in human peripheral blood. J Immunol 2000; 165: 6037-6046
  • 26 Dzionek A, Sohma Y, Nagafune J et al. BDCA-2, a novel plasmacytoid dendritic cell-specific type II C-type lectin, mediates antigen capture and is a potent inhibitor of interferon alpha/beta induction. J Exp Med 2001; 194: 1823-1834
  • 27 Dzionek A, Inagaki Y, Okawa K et al. Plasmacytoid dendritic cells: from specific surface markers to specific cellular functions(1). Hum Immunol 2002; 63: 1133-1148
  • 28 Radford KJ, Tullett KM, Lahoud MH. Dendritic cells and cancer immunotherapy. Curr Opin Immunol 2014; 27: 26-32
  • 29 Pulendran B, Palucka K, Banchereau J. Sensing pathogens and tuning immune responses. Science 2001; 293: 253-256
  • 30 Palucka K, Ueno H, Fay J et al. Harnessing dendritic cells to generate cancer vaccines. Ann N Y Acad Sci 2009; 1174: 88-98
  • 31 Palucka K, Banchereau J. Dendritic-cell-based therapeutic cancer vaccines. Immunity 2013; 39: 38-48
  • 32 Tel J, Anguille S, Waterborg CEJ et al. Tumoricidal activity of human dendritic cells. Trends Immunol 2014; 35: 38-46
  • 33 Tel J, Schreibelt G, Sittig SP et al. Human plasmacytoid dendritic cells efficiently cross-present exogenous Ags to CD8+ T cells despite lower Ag uptake than myeloid dendritic cell subsets. Blood 2013; 121: 459-467
  • 34 Siegal FP, Kadowaki N, Shodell M et al. The nature of the principal type 1 interferon-producing cells in human blood. Science 1999; 284: 1835-1837
  • 35 Gilliet M, Boonstra A, Paturel C et al. The development of murine plasmacytoid dendritic cell precursors is differentially regulated by FLT3-ligand and granulocyte/macrophage colony-stimulating factor. J Exp Med 2002; 195: 953-958
  • 36 Cella M, Facchetti F, Lanzavecchia A et al. Plasmacytoid dendritic cells activated by influenza virus and CD40 L drive a potent TH1 polarization. Nat Immunol 2000; 1: 305-310
  • 37 Santana-de Anda K, Gomez-Martin D, Soto-Solis R et al. Plasmacytoid dendritic cells: key players in viral infections and autoimmune diseases. Semin Arthritis Rheum 2013; 43: 131-136
  • 38 Tel J, van der Leun AM, Figdor CG et al. Harnessing human plasmacytoid dendritic cells as professional APCs. Cancer Immunol Immunother 2012; 61: 1279-1288
  • 39 Tel J, de Vries IJM. Potential applications for plasmacytoid dendritic cells in cancer immunotherapy. Immunotherapy 2012; 4: 979-982
  • 40 Schutz F, Hackstein H. Identification of novel dendritic cell subset markers in human blood. Biochem Biophys Res Commun 2014; 443: 453-457
  • 41 Ohnuma K, Dang NH, Morimoto C. Revisiting an old acquaintance: CD26 and its molecular mechanisms in T cell function. Trends Immunol 2008; 29: 295-301
  • 42 Matteucci E, Giampietro O. Dipeptidyl peptidase-4 (CD26): knowing the function before inhibiting the enzyme. Curr Med Chem 2009; 16: 2943-2951
  • 43 Lichterfeld M, Yu XG. The emerging role of leukocyte immunoglobulin-like receptors (LILRs) in HIV-1 infection. J Leukoc Biol 2012; 91: 27-33
  • 44 Huang J, Burke PS, Cung TDH et al. Leukocyte immunoglobulin-like receptors maintain unique antigen-presenting properties of circulating myeloid dendritic cells in HIV-1-infected elite controllers. J Virol 2010; 84: 9463-9471
  • 45 Draube A, Klein-Gonzalez N, Mattheus S et al. Dendritic cell based tumor vaccination in prostate and renal cell cancer: a systematic review and meta-analysis. PLoS One 2011; 6: e18801
  • 46 Kantoff PW, Higano CS, Shore ND et al. Sipuleucel-T immunotherapy for castration-resistant prostate cancer. N Engl J Med 2010; 363: 411-422
  • 47 Higano CS, Small EJ, Schellhammer P et al. Sipuleucel-T. Nat Rev Drug Discov 2010; 9: 513-514
  • 48 Tel J, Aarntzen EHJG, Baba T et al. Natural human plasmacytoid dendritic cells induce antigen-specific T-cell responses in melanoma patients. Cancer Res 2013; 73: 1063-1075
  • 49 de Vries IJM, Tel J, Benitez-Ribas D et al. Prophylactic vaccines mimic synthetic CpG oligonucleotides in their ability to modulate immune responses. Mol Immunol 2011; 48: 810-817
  • 50 Schreibelt G, Benitez-Ribas D, Schuurhuis D et al. Commonly used prophylactic vaccines as an alternative for synthetically produced TLR ligands to mature monocyte-derived dendritic cells. Blood 2010; 116: 564-574
  • 51 Vanham G, van Gulck E. Can immunotherapy be useful as a “functional cure” for infection with Human Immunodeficiency Virus-1?. Retrovirology 2012; 9: 72
  • 52 Garcia F, Leon A, Gatell JM et al. Therapeutic vaccines against HIV infection. Hum Vaccin Immunother 2012; 8: 569-581
  • 53 Garcia F, Routy J. Challenges in dendritic cells-based therapeutic vaccination in HIV-1 infection Workshop in dendritic cell-based vaccine clinical trials in HIV-1. Vaccine 2011; 29: 6454-6463
  • 54 Plana M, Garcia F, Gallart T et al. Lack of T-cell proliferative response to HIV-1 antigens after 1 year of highly active antiretroviral treatment in early HIV-1 disease. Immunology Study Group of Spanish EARTH-1 Study. Lancet 1998; 352: 1194-1195
  • 55 Lecuroux C, Girault I, Cheret A et al. CD8 T-cells from most HIV-infected patients lack ex vivo HIV-suppressive capacity during acute and early infection. PLoS One 2013; 8: e59767
  • 56 Genovese L, Nebuloni M, Alfano M. Cell-Mediated Immunity in Elite Controllers Naturally Controlling HIV Viral Load. Front Immunol 2013; 4: 86
  • 57 Saez-Cirion A, Lacabaratz C, Lambotte O et al. HIV controllers exhibit potent CD8 T cell capacity to suppress HIV infection ex vivo and peculiar cytotoxic T lymphocyte activation phenotype. Proc Natl Acad Sci USA 2007; 104: 6776-6781
  • 58 Migueles SA, Laborico AC, Shupert WL et al. HIV-specific CD8+ T cell proliferation is coupled to perforin expression and is maintained in nonprogressors. Nat Immunol 2002; 3: 1061-1068
  • 59 Migueles SA, Osborne CM, Royce C et al. Lytic granule loading of CD8+ T cells is required for HIV-infected cell elimination associated with immune control. Immunity 2008; 29: 1009-1021
  • 60 Betts MR, Nason MC, West SM et al. HIV nonprogressors preferentially maintain highly functional HIV-specific CD8+ T cells. Blood 2006; 107: 4781-4789
  • 61 Lu W, Arraes LC, Ferreira WT et al. Therapeutic dendritic-cell vaccine for chronic HIV-1 infection. Nat Med 2004; 10: 1359-1365
  • 62 Lu W, Wu X, Lu Y et al. Therapeutic dendritic-cell vaccine for simian AIDS. Nat Med 2003; 9: 27-32
  • 63 Garcia F, Climent N, Assoumou L et al. A therapeutic dendritic cell-based vaccine for HIV-1 infection. J Infect Dis 2011; 203: 473-478
  • 64 Watanabe N, Wang Y, Lee HK et al. Hassallʼs corpuscles instruct dendritic cells to induce CD4+CD25+ regulatory T cells in human thymus. Nature 2005; 436: 1181-1185
  • 65 Hanabuchi S, Ito T, Park W et al. Thymic stromal lymphopoietin-activated plasmacytoid dendritic cells induce the generation of FOXP3+ regulatory T cells in human thymus. J Immunol 2010; 184: 2999-3007
  • 66 Morelli AE, Thomson AW. Tolerogenic dendritic cells and the quest for transplant tolerance. Nat Rev Immunol 2007; 7: 610-621
  • 67 Vassalli G. Dendritic Cell-Based Approaches for Therapeutic Immune Regulation in Solid-Organ Transplantation. J Transplant 2013; 2013 Article ID 761429
  • 68 Gordon JR, Ma Y, Churchman L et al. Regulatory Dendritic Cells for Immunotherapy in Immunologic Diseases. Front Immunol 2014; 5: 7
  • 69 Dhodapkar MV, Steinman RM, Krasovsky J et al. Antigen-specific inhibition of effector T cell function in humans after injection of immature dendritic cells. J Exp Med 2001; 193: 233-238
  • 70 Dhodapkar MV, Steinman RM. Antigen-bearing immature dendritic cells induce peptide-specific CD8(+) regulatory T cells in vivo in humans. Blood 2002; 100: 174-177
  • 71 Giannoukakis N, Phillips B, Finegold D et al. Phase I (safety) study of autologous tolerogenic dendritic cells in type 1 diabetic patients. Diabetes Care 2011; 34: 2026-2032
  • 72 Hilkens CMU, Isaacs JD. Tolerogenic dendritic cell therapy for rheumatoid arthritis: where are we now?. Clin Exp Immunol 2013; 172: 148-157
  • 73 Nel H, Law S, Street S et al. Outcome of a Phase I Trial of rheumavax in patients with rheumatoid arthritis: ARA Scientific Posters. Internal Medicine Journal 2012; 42 (Suppl. 01) 9-35
  • 74 Moreau A, Varey E, Bouchet-Delbos L et al. Cell therapy using tolerogenic dendritic cells in transplantation. Transplant Res 2012; 1: 13
  • 75 Unger WWJ, van Kooyk Y. ‘Dressed for success’ C-type lectin receptors for the delivery of glyco-vaccines to dendritic cells. Curr Opin Immunol 2011; 23: 131-137
  • 76 Torabi-Rahvar M, Bozorgmehr M, Jeddi-Tehrani M et al. Potentiation strategies of dendritic cell-based antitumor vaccines: combinational therapy takes the front seat. Drug Discov Today 2011; 16: 733-740