Cancer Immunology, Immunotherapy

, Volume 56, Issue 10, pp 1513–1537

Current approaches in dendritic cell generation and future implications for cancer immunotherapy

  • Sandra Tuyaerts
  • Joeri L. Aerts
  • Jurgen Corthals
  • Bart Neyns
  • Carlo Heirman
  • Karine Breckpot
  • Kris Thielemans
  • Aude Bonehill
Review
  • 662 Downloads

Abstract

The discovery of tumor-associated antigens, which are either selectively or preferentially expressed by tumors, together with an improved insight in dendritic cell biology illustrating their key function in the immune system, have provided a rationale to initiate dendritic cell-based cancer immunotherapy trials. Nevertheless, dendritic cell vaccination is in an early stage, as methods for preparing tumor antigen presenting dendritic cells and improving their immunostimulatory function are continuously being optimized. In addition, recent improvements in immunomonitoring have emphasized the need for careful design of this part of the trials. Still, valuable proofs-of-principle have been obtained, which favor the use of dendritic cells in subsequent, more standardized clinical trials. Here, we review the recent developments in clinical DC generation, antigen loading methods and immunomonitoring approaches for DC-based trials.

Keywords

Clinical applicability Dendritic cell Cancer immunotherapy 

References

  1. 1.
    Adams M, Navabi H, Jasani B, Man S, Fiander A, Evans AS, Donninger C, Mason M (2003) Dendritic cell (DC) based therapy for cervical cancer: use of DC pulsed with tumour lysate and matured with a novel synthetic clinically non-toxic double stranded RNA analogue poly [I]:poly [C(12)U] (Ampligen R). Vaccine 21:787–790PubMedCrossRefGoogle Scholar
  2. 2.
    Adamson L, Palmborg A, Svensson A, Lundqvist A, Hansson M, Kiessling R, Masucci G, Mellstedt H, Pisa P (2004) Development of a technology platform for large-scale clinical grade production of DC. Cytotherapy 6:363–371PubMedCrossRefGoogle Scholar
  3. 3.
    Aerts-Toegaert C, Heirman C, Tuyaerts S, Corthals J, Aerts JL, Bonehill A, Thielemans K, Breckpot K (2007) CD83 expression on dendritic cells and T cells: Correlation with effective immune responses. Eur J Immunol 37:686–695PubMedCrossRefGoogle Scholar
  4. 4.
    Alejandro Lopez J, Crosbie G, Kelly C, McGee AM, Williams K, Vuckovic S, Schuyler R, Rodwell R, Wright SJ, Taylor K, Hart DN (2002) Monitoring and isolation of blood dendritic cells from apheresis products in healthy individuals: a platform for cancer immunotherapy. J Immunol Methods 267:199–212PubMedCrossRefGoogle Scholar
  5. 5.
    Almand B, Resser JR, Lindman B, Nadaf S, Clark JI, Kwon ED, Carbone DP, Gabrilovich DI (2000) Clinical significance of defective dendritic cell differentiation in cancer. Clin Cancer Res 6:1755–1766PubMedGoogle Scholar
  6. 6.
    Andersen MH, Schrama D, Thor Straten P, Becker JC (2006) Cytotoxic T cells. J Invest Dermatol 126:32–41PubMedCrossRefGoogle Scholar
  7. 7.
    Andre F, Chaput N, Schartz NE, Flament C, Aubert N, Bernard J, Lemonnier F, Raposo G, Escudier B, Hsu DH, Tursz T, Amigorena S, Angevin E, Zitvogel L (2004) Exosomes as potent cell-free peptide-based vaccine. I. Dendritic cell-derived exosomes transfer functional MHC class I/peptide complexes to dendritic cells. J Immunol 172:2126–2136PubMedGoogle Scholar
  8. 8.
    Appay V, Jandus C, Voelter V, Reynard S, Coupland SE, Rimoldi D, Lienard D, Guillaume P, Krieg AM, Cerottini JC, Romero P, Leyvraz S, Rufer N, Speiser DE (2006) New generation vaccine induces effective melanoma-specific CD8+ T cells in the circulation but not in the tumor site. J Immunol 177:1670–1678PubMedGoogle Scholar
  9. 9.
    Attia P, Powell DJ Jr, Maker AV, Kreitman RJ, Pastan I, Rosenberg SA (2006) Selective elimination of human regulatory T lymphocytes in vitro with the recombinant immunotoxin LMB-2. J Immunother 29:208–214PubMedCrossRefGoogle Scholar
  10. 10.
    Babatz J, Rollig C, Oelschlagel U, Zhao S, Ehninger G, Schmitz M, Bornhauser M (2003) Large-scale immunomagnetic selection of CD14+ monocytes to generate dendritic cells for cancer immunotherapy: a phase I study. J Hematother Stem Cell Res 12:515–523PubMedCrossRefGoogle Scholar
  11. 11.
    Bai L, Feuerer M, Beckhove P, Umansky V, Schirrmacher V (2002) Generation of dendritic cells from human bone marrow mononuclear cells: advantages for clinical application in comparison to peripheral blood monocyte derived cells. Int J Oncol 20:247–253PubMedGoogle Scholar
  12. 12.
    Banchereau J, Briere F, Caux C, Davoust J, Lebecque S, Liu YJ, Pulendran B, Palucka K (2000) Immunobiology of dendritic cells. Annu Rev Immunol 18:767–811PubMedCrossRefGoogle Scholar
  13. 13.
    Banchereau J, Palucka AK (2005) Dendritic cells as therapeutic vaccines against cancer. Nat Rev Immunol 5:296–306PubMedCrossRefGoogle Scholar
  14. 14.
    Banerjee D, Dhodapkar MV, Matayeva E, Steinman RM, Dhodapkar K (2006) Expansion of FOXP3high regulatory T cells by human dendritic cells (DCs) in vitro and after DC injection of cytokine matured DCs in myeloma patients. Blood 108:2655–2661PubMedCrossRefGoogle Scholar
  15. 15.
    Bedrosian I, Mick R, Xu S, Nisenbaum H, Faries M, Zhang P, Cohen PA, Koski G, Czerniecki BJ (2003) Intranodal administration of peptide-pulsed mature dendritic cell vaccines results in superior CD8+ T-cell function in melanoma patients. J Clin Oncol 21:3826–3835PubMedCrossRefGoogle Scholar
  16. 16.
    Bergant M, Meden L, Repnik U, Sojar V, Stanisavljevic D, Jeras M (2006) Preparation of native and amplified tumour RNA for dendritic cell transfection and generation of in vitro anti-tumour CTL responses. Immunobiology 211:179–189PubMedCrossRefGoogle Scholar
  17. 17.
    Berger TG, Feuerstein B, Strasser E, Hirsch U, Schreiner D, Schuler G, Schuler-Thurner B (2002) Large-scale generation of mature monocyte-derived dendritic cells for clinical application in cell factories. J Immunol Methods 268:131–140PubMedCrossRefGoogle Scholar
  18. 18.
    Berger TG, Strasser E, Smith R, Carste C, Schuler-Thurner B, Kaempgen E, Schuler G (2005) Efficient elutriation of monocytes within a closed system (Elutra) for clinical-scale generation of dendritic cells. J Immunol Methods 298:61–72PubMedCrossRefGoogle Scholar
  19. 19.
    Betts MR, Brenchley JM, Price DA, De Rosa SC, Douek DC, Roederer M, Koup RA (2003) Sensitive and viable identification of antigen-specific CD8+ T cells by a flow cytometric assay for degranulation. J Immunol Methods 281:65–78PubMedCrossRefGoogle Scholar
  20. 20.
    Bevan MJ (2004) Helping the CD8(+) T-cell response. Nat Rev Immunol 4:595–602PubMedCrossRefGoogle Scholar
  21. 21.
    Bohnenkamp HR, Coleman J, Burchell JM, Taylor-Papadimitriou J, Noll T (2004) Breast carcinoma cell lysate-pulsed dendritic cells cross-prime MUC1-specific CD8+ T cells identified by peptide-MHC-class-I tetramers. Cell Immunol 231:112–125PubMedCrossRefGoogle Scholar
  22. 22.
    Boon T, Coulie PG, Van den Eynde BJ, van der Bruggen P (2006) Human T cell responses against melanoma. Annu Rev Immunol 24:175–208PubMedCrossRefGoogle Scholar
  23. 23.
    Boon T, van der Bruggen P (1996) Human tumor antigens recognized by T lymphocytes. J Exp Med 183:725–729PubMedCrossRefGoogle Scholar
  24. 24.
    Breckpot K, Corthals J, Bonehill A, Michiels A, Tuyaerts S, Aerts C, Heirman C, Thielemans K (2005) Dendritic cells differentiated in the presence of IFN-{beta} and IL-3 are potent inducers of an antigen-specific CD8+ T cell response. J Leukoc Biol 78:898–908PubMedCrossRefGoogle Scholar
  25. 25.
    Breckpot K, Corthals J, Heirman C, Bonehill A, Michiels A, Tuyaerts S, De Greef C, Thielemans K (2004) Activation of monocytes via the CD14 receptor leads to the enhanced lentiviral transduction of immature dendritic cells. Hum Gene Ther 15:562–573PubMedCrossRefGoogle Scholar
  26. 26.
    Breckpot K, Heirman C, Neyns B, Thielemans K (2004) Exploiting dendritic cells for cancer immunotherapy: genetic modification of dendritic cells. J Gene Med 6:1175–1188PubMedCrossRefGoogle Scholar
  27. 27.
    Brossart P, Wirths S, Stuhler G, Reichardt VL, Kanz L, Brugger W (2000) Induction of cytotoxic T-lymphocyte responses in vivo after vaccinations with peptide-pulsed dendritic cells. Blood 96:3102–3108PubMedGoogle Scholar
  28. 28.
    Brosterhus H, Brings S, Leyendeckers H, Manz RA, Miltenyi S, Radbruch A, Assenmacher M, Schmitz J (1999) Enrichment and detection of live antigen-specific CD4(+) and CD8(+) T cells based on cytokine secretion. Eur J Immunol 29:4053–4059PubMedCrossRefGoogle Scholar
  29. 29.
    Buelens C, Bartholome EJ, Amraoui Z, Boutriaux M, Salmon I, Thielemans K, Willems F, Goldman M (2002) Interleukin-3 and interferon beta cooperate to induce differentiation of monocytes into dendritic cells with potent helper T-cell stimulatory properties. Blood 99:993–998PubMedCrossRefGoogle Scholar
  30. 30.
    Butterfield LH, Ribas A, Dissette VB, Amarnani SN, Vu HT, Oseguera D, Wang HJ, Elashoff RM, McBride WH, Mukherji B, Cochran AJ, Glaspy JA, Economou JS (2003) Determinant spreading associated with clinical response in dendritic cell-based immunotherapy for malignant melanoma. Clin Cancer Res 9:998–1008PubMedGoogle Scholar
  31. 31.
    Campbell JD, Piechaczek C, Winkels G, Schwamborn E, Micheli D, Hennemann S, Schmitz J (2005) Isolation and generation of clinical-grade dendritic cells using the CliniMACS system. Methods Mol Med 109:55–70PubMedGoogle Scholar
  32. 32.
    Cappello P, Fraone T, Barberis L, Costa C, Hirsch E, Elia AR, Caorsi C, Musso T, Novelli F, Giovarelli M (2006) CC-chemokine ligand 16 induces a novel maturation program in human immature monocyte-derived dendritic cells. J Immunol 177:6143–6151PubMedGoogle Scholar
  33. 33.
    Carrasco J, Godelaine D, Van Pel A, Boon T, van der Bruggen P (2006) CD45RA on human CD8 T cells is sensitive to the time elapsed since the last antigenic stimulation. Blood 108:2897–2905PubMedCrossRefGoogle Scholar
  34. 34.
    Celluzzi CM, Welbon C (2003) Dendritic cell culture: a simple closed culture system using ficoll, monocytes, and a table-top centrifuge. J Hematother Stem Cell Res 12:575–585PubMedCrossRefGoogle Scholar
  35. 35.
    Cham CM, Gajewski TF (2005) Metabolic mechanisms of tumor resistance to T cell effector function. Immunol Res 31:107–118PubMedCrossRefGoogle Scholar
  36. 36.
    Chaput N, Schartz NE, Andre F, Taieb J, Novault S, Bonnaventure P, Aubert N, Bernard J, Lemonnier F, Merad M, Adema G, Adams M, Ferrantini M, Carpentier AF, Escudier B, Tursz T, Angevin E, Zitvogel L (2004) Exosomes as potent cell-free peptide-based vaccine. II. Exosomes in CpG adjuvants efficiently prime naive Tc1 lymphocytes leading to tumor rejection. J Immunol 172:2137–2146PubMedGoogle Scholar
  37. 37.
    Chen B, Stiff P, Sloan G, Kash J, Manjunath R, Pathasarathy M, Oldenburg D, Foreman KE, Nickoloff BJ (2001) Replicative response, immunophenotype, and functional activity of monocyte-derived versus CD34(+)-derived dendritic cells following exposure to various expansion and maturational stimuli. Clin Immunol 98:280–292PubMedCrossRefGoogle Scholar
  38. 38.
    Chen CH, Wu TC (1998) Experimental vaccine strategies for cancer immunotherapy. J Biomed Sci 5:231–252PubMedCrossRefGoogle Scholar
  39. 39.
    Chen Y, Yang C, Jin N, Xie Z, Tang Y, Fei L, Jia Z, Wu Y (2007) Terminal complement complex C5b-9-treated human monocyte-derived dendritic cells undergo maturation and induce Th1 polarization. Eur J Immunol 37:167–176PubMedCrossRefGoogle Scholar
  40. 40.
    Coulie PG, Connerotte T (2005) Human tumor-specific T lymphocytes: does function matter more than number? Curr Opin Immunol 17:320–325PubMedCrossRefGoogle Scholar
  41. 41.
    Coulie PG, van der Bruggen P (2003) T-cell responses of vaccinated cancer patients. Curr Opin Immunol 15:131–137PubMedCrossRefGoogle Scholar
  42. 42.
    Curiel TJ, Coukos G, Zou L, Alvarez X, Cheng P, Mottram P, Evdemon-Hogan M, Conejo-Garcia JR, Zhang L, Burow M, Zhu Y, Wei S, Kryczek I, Daniel B, Gordon A, Myers L, Lackner A, Disis ML, Knutson KL, Chen L, Zou W (2004) Specific recruitment of regulatory T cells in ovarian carcinoma fosters immune privilege and predicts reduced survival. Nat Med 10:942–949PubMedCrossRefGoogle Scholar
  43. 43.
    Dakic A, Wu L (2003) Hemopoietic precursors and development of dendritic cell populations. Leuk Lymphoma 44:1469–1475PubMedCrossRefGoogle Scholar
  44. 44.
    Dannull J, Su Z, Rizzieri D, Yang BK, Coleman D, Yancey D, Zhang A, Dahm P, Chao N, Gilboa E, Vieweg J (2005) Enhancement of vaccine-mediated antitumor immunity in cancer patients after depletion of regulatory T cells. J Clin Invest 115:3623–3633PubMedCrossRefGoogle Scholar
  45. 45.
    Dauer M, Pohl K, Obermaier B, Meskendahl T, Robe J, Schnurr M, Endres S, Eigler A (2003) Interferon-alpha disables dendritic cell precursors: dendritic cells derived from interferon-alpha-treated monocytes are defective in maturation and T-cell stimulation. Immunology 110:38–47PubMedCrossRefGoogle Scholar
  46. 46.
    Dauer M, Schad K, Herten J, Junkmann J, Bauer C, Kiefl R, Endres S, Eigler A (2005) FastDC derived from human monocytes within 48 h effectively prime tumor antigen-specific cytotoxic T cells. J Immunol Methods 302:145–155PubMedCrossRefGoogle Scholar
  47. 47.
    de Vries IJ, Bernsen MR, Lesterhuis WJ, Scharenborg NM, Strijk SP, Gerritsen MJ, Ruiter DJ, Figdor CG, Punt CJ, Adema GJ (2005) Immunomonitoring tumor-specific T cells in delayed-type hypersensitivity skin biopsies after dendritic cell vaccination correlates with clinical outcome. J Clin Oncol 23:5779–5787PubMedCrossRefGoogle Scholar
  48. 48.
    de Vries IJ, Lesterhuis WJ, Scharenborg NM, Engelen LP, Ruiter DJ, Gerritsen MJ, Croockewit S, Britten CM, Torensma R, Adema GJ, Figdor CG, Punt CJ (2003) Maturation of dendritic cells is a prerequisite for inducing immune responses in advanced melanoma patients. Clin Cancer Res 9:5091–5100PubMedGoogle Scholar
  49. 49.
    Della Bella S, Nicola S, Riva A, Biasin M, Clerici M, Villa ML (2004) Functional repertoire of dendritic cells generated in granulocyte macrophage-colony stimulating factor and interferon-alpha. J Leukoc Biol 75:106–116PubMedCrossRefGoogle Scholar
  50. 50.
    Della Porta M, Danova M, Rigolin GM, Brugnatelli S, Rovati B, Tronconi C, Fraulini C, Russo Rossi A, Riccardi A, Castoldi G (2005) Dendritic cells and vascular endothelial growth factor in colorectal cancer: correlations with clinicobiological findings. Oncology 68:276–284PubMedCrossRefGoogle Scholar
  51. 51.
    Delluc S, Tourneur L, Fradelizi D, Rubio MT, Marchiol-Fournigault C, Chiocchia G, Buzyn A (2007) DC-based vaccine loaded with acid-eluted peptides in acute myeloid leukemia: the importance of choosing the best elution method. Cancer Immunol Immunother 56:1–12PubMedCrossRefGoogle Scholar
  52. 52.
    Dietz AB, Padley DJ, Butler GW, Maas ML, Greiner CW, Gastineau DA, Vuk-Pavlovic S (2004) Clinical-grade manufacturing of DC from CD14+ precursors: experience from phase I clinical trials in CML and malignant melanoma. Cytotherapy 6:563–570PubMedCrossRefGoogle Scholar
  53. 53.
    Dunn GP, Koebel CM, Schreiber RD (2006) Interferons, immunity and cancer immunoediting. Nat Rev Immunol 6:836–848PubMedCrossRefGoogle Scholar
  54. 54.
    Elkord E, Williams PE, Kynaston H, Rowbottom AW (2005) Human monocyte isolation methods influence cytokine production from in vitro generated dendritic cells. Immunology 114:204–212PubMedCrossRefGoogle Scholar
  55. 55.
    Escudier B, Dorval T, Chaput N, Andre F, Caby MP, Novault S, Flament C, Leboulaire C, Borg C, Amigorena S, Boccaccio C, Bonnerot C, Dhellin O, Movassagh M, Piperno S, Robert C, Serra V, Valente N, Le Pecq JB, Spatz A, Lantz O, Tursz T, Angevin E, Zitvogel L (2005) Vaccination of metastatic melanoma patients with autologous dendritic cell (DC) derived-exosomes: results of the first phase I clinical trial. J Transl Med 3:10PubMedCrossRefGoogle Scholar
  56. 56.
    Fearnley DB, McLellan AD, Mannering SI, Hock BD, Hart DN (1997) Isolation of human blood dendritic cells using the CMRF-44 monoclonal antibody: implications for studies on antigen-presenting cell function and immunotherapy. Blood 89:3708–3716PubMedGoogle Scholar
  57. 57.
    Felzmann T, Witt V, Wimmer D, Ressmann G, Wagner D, Paul P, Huttner K, Fritsch G (2003) Monocyte enrichment from leukapharesis products for the generation of DCs by plastic adherence, or by positive or negative selection. Cytotherapy 5:391–398PubMedCrossRefGoogle Scholar
  58. 58.
    Ferlazzo G, Semino C, Spaggiari GM, Meta M, Mingari MC, Melioli G (2000) Dendritic cells efficiently cross-prime HLA class I-restricted cytolytic T lymphocytes when pulsed with both apoptotic and necrotic cells but not with soluble cell-derived lysates. Int Immunol 12:1741–1747PubMedCrossRefGoogle Scholar
  59. 59.
    Feuerstein B, Berger TG, Maczek C, Roder C, Schreiner D, Hirsch U, Haendle I, Leisgang W, Glaser A, Kuss O, Diepgen TL, Schuler G, Schuler-Thurner B (2000) A method for the production of cryopreserved aliquots of antigen-preloaded, mature dendritic cells ready for clinical use. J Immunol Methods 245:15–29PubMedCrossRefGoogle Scholar
  60. 60.
    Figdor CG, de Vries IJ, Lesterhuis WJ, Melief CJ (2004) Dendritic cell immunotherapy: mapping the way. Nat Med 10:475–480PubMedCrossRefGoogle Scholar
  61. 61.
    Fong L, Brockstedt D, Benike C, Wu L, Engleman EG (2001) Dendritic cells injected via different routes induce immunity in cancer patients. J Immunol 166:4254–4259PubMedGoogle Scholar
  62. 62.
    Fong L, Hou Y, Rivas A, Benike C, Yuen A, Fisher GA, Davis MM, Engleman EG (2001) Altered peptide ligand vaccination with Flt3 ligand expanded dendritic cells for tumor immunotherapy. Proc Natl Acad Sci USA 98:8809–8814PubMedCrossRefGoogle Scholar
  63. 63.
    Franzke A (2006) The role of G-CSF in adaptive immunity. Cytokine Growth Factor Rev 17:235–244PubMedCrossRefGoogle Scholar
  64. 64.
    Gajewski TF, Meng Y, Harlin H (2006) Immune suppression in the tumor microenvironment. J Immunother 29:233–240PubMedCrossRefGoogle Scholar
  65. 65.
    Garderet L, Cao H, Salamero J, Verge V, Tisserand E, Scholl S, Gorin NC, Lopez M (2001) In vitro production of dendritic cells from human blood monocytes for therapeutic use. J Hematother Stem Cell Res 10:553–567PubMedCrossRefGoogle Scholar
  66. 66.
    Garlie N, Timler A (2005) Dendritic cell generation from cryopreserved monocytes enriched using the Elutra versus the CliniMACS Cell Separation Systems. J Immunother 28:613–613CrossRefGoogle Scholar
  67. 67.
    Gervois N, Heuze F, Diez E, Jotereau F (1990) Selective expansion of a specific anti-tumor CD8+ cytotoxic T lymphocyte clone in the bulk culture of tumor-infiltrating lymphocytes from a melanoma patient: cytotoxic activity and T cell receptor gene rearrangements. Eur J Immunol 20:825–831PubMedCrossRefGoogle Scholar
  68. 68.
    Ghiringhelli F, Menard C, Puig PE, Ladoire S, Roux S, Martin F, Solary E, Le Cesne A, Zitvogel L, Chauffert B (2007) Metronomic cyclophosphamide regimen selectively depletes CD4(+)CD25 (+) regulatory T cells and restores T and NK effector functions in end stage cancer patients. Cancer Immunol Immunother 56:641–648PubMedCrossRefGoogle Scholar
  69. 69.
    Gilboa E, Vieweg J (2004) Cancer immunotherapy with mRNA-transfected dendritic cells. Immunol Rev 199:251–263PubMedCrossRefGoogle Scholar
  70. 70.
    Godelaine D, Carrasco J, Lucas S, Karanikas V, Schuler-Thurner B, Coulie PG, Schuler G, Boon T, Van Pel A (2003) Polyclonal CTL responses observed in melanoma patients vaccinated with dendritic cells pulsed with a MAGE-3.A1 peptide. J Immunol 171:4893–4897PubMedGoogle Scholar
  71. 71.
    Gordan JD, Vonderheide RH (2002) Universal tumor antigens as targets for immunotherapy. Cytotherapy 4:317–327PubMedCrossRefGoogle Scholar
  72. 72.
    Guardino AE, Rajapaksa R, Ong KH, Sheehan K, Levy R (2006) Production of myeloid dendritic cells (DC) pulsed with tumor-specific idiotype protein for vaccination of patients with multiple myeloma. Cytotherapy 8:277–289PubMedCrossRefGoogle Scholar
  73. 73.
    Guermonprez P, Valladeau J, Zitvogel L, Thery C, Amigorena S (2002) Antigen presentation and T cell stimulation by dendritic cells. Annu Rev Immunol 20:621–667PubMedCrossRefGoogle Scholar
  74. 74.
    Hayakawa S (2006) No cancer in cancers: evolutionary trade-off between successful viviparity and tumor escape from the adaptive immune system. Med Hypotheses 66:888–897PubMedCrossRefGoogle Scholar
  75. 75.
    Holtl L, Ramoner R, Zelle-Rieser C, Gander H, Putz T, Papesh C, Nussbaumer W, Falkensammer C, Bartsch G, Thurnher M (2005) Allogeneic dendritic cell vaccination against metastatic renal cell carcinoma with or without cyclophosphamide. Cancer Immunol Immunother 54:663–670PubMedCrossRefGoogle Scholar
  76. 76.
    Hoos A, Parmiani G, Hege K, Sznol M, Loibner H, Eggermont A, Urba W, Blumenstein B, Sacks N, Keilholz U, Nichol G (2007) A clinical development paradigm for cancer vaccines and related biologics. J Immunother 30:1–15PubMedCrossRefGoogle Scholar
  77. 77.
    Jarnjak-Jankovic S, Pettersen RD, Saeboe-Larssen S, Wesenberg F, Gaudernack G (2005) Evaluation of dendritic cells loaded with apoptotic cancer cells or expressing tumour mRNA as potential cancer vaccines against leukemia. BMC Cancer 5:20PubMedCrossRefGoogle Scholar
  78. 78.
    Jarrossay D, Napolitani G, Colonna M, Sallusto F, Lanzavecchia A (2001) Specialization and complementarity in microbial molecule recognition by human myeloid and plasmacytoid dendritic cells. Eur J Immunol 31:3388–3393PubMedCrossRefGoogle Scholar
  79. 79.
    Jefford M, Schnurr M, Toy T, Masterman KA, Shin A, Beecroft T, Tai TY, Shortman K, Shackleton M, Davis ID, Parente P, Luft T, Chen W, Cebon J, Maraskovsky E (2003) Functional comparison of DCs generated in vivo with Flt3 ligand or in vitro from blood monocytes: differential regulation of function by specific classes of physiologic stimuli. Blood 102:1753–1763PubMedCrossRefGoogle Scholar
  80. 80.
    Jonuleit H, Giesecke-Tuettenberg A, Tuting T, Thurner-Schuler B, Stuge TB, Paragnik L, Kandemir A, Lee PP, Schuler G, Knop J, Enk AH (2001) A comparison of two types of dendritic cell as adjuvants for the induction of melanoma-specific T-cell responses in humans following intranodal injection. Int J Cancer 93:243–251PubMedCrossRefGoogle Scholar
  81. 81.
    Kammula US, Lee KH, Riker AI, Wang E, Ohnmacht GA, Rosenberg SA, Marincola FM (1999) Functional analysis of antigen-specific T lymphocytes by serial measurement of gene expression in peripheral blood mononuclear cells and tumor specimens. J Immunol 163:6867–6875PubMedGoogle Scholar
  82. 82.
    Kammula US, Marincola FM, Rosenberg SA (2000) Real-time quantitative polymerase chain reaction assessment of immune reactivity in melanoma patients after tumor peptide vaccination. J Natl Cancer Inst 92:1336–1344PubMedCrossRefGoogle Scholar
  83. 83.
    Karanikas V, Lurquin C, Colau D, van Baren N, De Smet C, Lethe B, Connerotte T, Corbiere V, Demoitie MA, Lienard D, Dreno B, Velu T, Boon T, Coulie PG (2003) Monoclonal anti-MAGE-3 CTL responses in melanoma patients displaying tumor regression after vaccination with a recombinant canarypox virus. J Immunol 171:4898–4904PubMedGoogle Scholar
  84. 84.
    Kato M, Neil TK, Fearnley DB, McLellan AD, Vuckovic S, Hart DN (2000) Expression of multilectin receptors and comparative FITC-dextran uptake by human dendritic cells. Int Immunol 12:1511–1519PubMedCrossRefGoogle Scholar
  85. 85.
    Keilholz U, Martus P, Scheibenbogen C (2006) Immune monitoring of T-cell responses in cancer vaccine development. Clin Cancer Res 12:2346s–2352sPubMedCrossRefGoogle Scholar
  86. 86.
    Klangsinsirikul P, Russell NH (2002) Peripheral blood stem cell harvests from G-CSF-stimulated donors contain a skewed Th2 CD4 phenotype and a predominance of type 2 dendritic cells. Exp Hematol 30:495–501PubMedCrossRefGoogle Scholar
  87. 87.
    Koido S, Nikrui N, Ohana M, Xia J, Tanaka Y, Liu C, Durfee JK, Lerner A, Gong J (2005) Assessment of fusion cells from patient-derived ovarian carcinoma cells and dendritic cells as a vaccine for clinical use. Gynecol Oncol 99:462–471PubMedCrossRefGoogle Scholar
  88. 88.
    Kufner S, Zitzelsberger H, Kroell T, Pelka-Fleischer R, Salem A, de Valle F, Schweiger C, Nuessler V, Schmid C, Kolb HJ, Schmetzer HM (2005) Leukemia-derived dendritic cells can be generated from blood or bone marrow cells from patients with acute myeloid leukaemia: a methodological approach under serum-free culture conditions. Scand J Immunol 62:86–98PubMedCrossRefGoogle Scholar
  89. 89.
    Kyte JA, Mu L, Aamdal S, Kvalheim G, Dueland S, Hauser M, Gullestad HP, Ryder T, Lislerud K, Hammerstad H, Gaudernack G (2006) Phase I/II trial of melanoma therapy with dendritic cells transfected with autologous tumor-mRNA. Cancer Gene Ther 13:905–918PubMedCrossRefGoogle Scholar
  90. 90.
    Lee AW, Truong T, Bickham K, Fonteneau JF, Larsson M, Da Silva I, Somersan S, Thomas EK, Bhardwaj N (2002) A clinical grade cocktail of cytokines and PGE2 results in uniform maturation of human monocyte-derived dendritic cells: implications for immunotherapy. Vaccine 20(suppl 4):A8–A22PubMedCrossRefGoogle Scholar
  91. 91.
    Lee KH, Panelli MC, Kim CJ, Riker AI, Bettinotti MP, Roden MM, Fetsch P, Abati A, Rosenberg SA, Marincola FM (1998) Functional dissociation between local and systemic immune response during anti-melanoma peptide vaccination. J Immunol 161:4183–4194PubMedGoogle Scholar
  92. 92.
    Lehner M, Felzmann T, Clodi K, Holter W (2001) Type I interferons in combination with bacterial stimuli induce apoptosis of monocyte-derived dendritic cells. Blood 98:736–742PubMedCrossRefGoogle Scholar
  93. 93.
    Lehner M, Holter W (2002) Endotoxin-free purification of monocytes for dendritic cell generation via discontinuous density gradient centrifugation based on diluted Ficoll-Paque Plus. Int Arch Allergy Immunol 128:73–76PubMedCrossRefGoogle Scholar
  94. 94.
    Lewalle P, Rouas R, Lehmann F, Martiat P (2000) Freezing of dendritic cells, generated from cryopreserved leukaphereses, does not influence their ability to induce antigen-specific immune responses or functionally react to maturation stimuli. J Immunol Methods 240:69–78PubMedCrossRefGoogle Scholar
  95. 95.
    Liu W, Putnam AL, Xu-Yu Z, Szot GL, Lee MR, Zhu S, Gottlieb PA, Kapranov P, Gingeras TR, Fazekas de St Groth B, Clayberger C, Soper DM, Ziegler SF, Bluestone JA (2006) CD127 expression inversely correlates with FoxP3 and suppressive function of human CD4+ T reg cells. J Exp Med 203:1701–1711PubMedCrossRefGoogle Scholar
  96. 96.
    Lizee G, Radvanyi LG, Overwijk WW, Hwu P (2006) Improving antitumor immune responses by circumventing immunoregulatory cells and mechanisms. Clin Cancer Res 12:4794–4803PubMedCrossRefGoogle Scholar
  97. 97.
    Lopez JA, Bioley G, Turtle CJ, Pinzon-Charry A, Ho CS, Vuckovic S, Crosbie G, Gilleece M, Jackson DC, Munster D, Hart DN (2003) Single step enrichment of blood dendritic cells by positive immunoselection. J Immunol Methods 274:47–61PubMedCrossRefGoogle Scholar
  98. 98.
    Lopez M, Amorim L, Gane P, Cristoph A, Bardinet D, Abina AM, Minty A, Bernard J (1997) IL-13 induces CD34+ cells isolated from G-CSF mobilized blood to differentiate in vitro into potent antigen presenting cells. J Immunol Methods 208:117–129PubMedCrossRefGoogle Scholar
  99. 99.
    Luft T, Pang KC, Thomas E, Bradley CJ, Savoia H, Trapani J, Cebon J (1998) A serum-free culture model for studying the differentiation of human dendritic cells from adult CD34+ progenitor cells. Exp Hematol 26:489–500PubMedGoogle Scholar
  100. 100.
    Lurquin C, Lethe B, De Plaen E, Corbiere V, Theate I, van Baren N, Coulie PG, Boon T (2005) Contrasting frequencies of antitumor and anti-vaccine T cells in metastases of a melanoma patient vaccinated with a MAGE tumor antigen. J Exp Med 201:249–257PubMedCrossRefGoogle Scholar
  101. 101.
    Lyons AB (1999) Divided we stand: tracking cell proliferation with carboxyfluorescein diacetate succinimidyl ester. Immunol Cell Biol 77:509–515PubMedCrossRefGoogle Scholar
  102. 102.
    Makino M, Wakamatsu S, Shimokubo S, Arima N, Baba M (2000) Production of functionally deficient dendritic cells from HTLV-I-infected monocytes: implications for the dendritic cell defect in adult T cell leukemia. Virology 274:140–148PubMedCrossRefGoogle Scholar
  103. 103.
    Maraskovsky E, Daro E, Roux E, Teepe M, Maliszewski CR, Hoek J, Caron D, Lebsack ME, McKenna HJ (2000) In vivo generation of human dendritic cell subsets by Flt3 ligand. Blood 96:878–884PubMedGoogle Scholar
  104. 104.
    Matzinger P (2002) The danger model: a renewed sense of self. Science 296:301–305PubMedCrossRefGoogle Scholar
  105. 105.
    McIlroy D, Gregoire M (2003) Optimizing dendritic cell-based anticancer immunotherapy: maturation state does have clinical impact. Cancer Immunol Immunother 52:583–591PubMedCrossRefGoogle Scholar
  106. 106.
    McRae BL, Nagai T, Semnani RT, van Seventer JM, van Seventer GA (2000) Interferon-alpha and -beta inhibit the in vitro differentiation of immunocompetent human dendritic cells from CD14(+) precursors. Blood 96:210–217PubMedGoogle Scholar
  107. 107.
    Messele T, Roos MT, Hamann D, Koot M, Fontanet AL, Miedema F, Schellekens PT, Rinke de Wit TF (2000) Nonradioactive techniques for measurement of in vitro T-cell proliferation: alternatives to the [(3)H]thymidine incorporation assay. Clin Diagn Lab Immunol 7:687–692PubMedCrossRefGoogle Scholar
  108. 108.
    Meyer-Wentrup F, Burdach S (2003) Efficacy of dendritic cell generation for clinical use: recovery and purity of monocytes and mature dendritic cells after immunomagnetic sorting or adherence selection of CD14+ starting populations. J Hematother Stem Cell Res 12:289–299PubMedCrossRefGoogle Scholar
  109. 109.
    Michiels A, Breckpot K, Corthals J, Tuyaerts S, Bonehill A, Heirman C, Thielemans K, Aerts JL (2006) Induction of antigen-specific CD8+ cytotoxic T cells by dendritic cells co-electroporated with a dsRNA analogue and tumor antigen mRNA. Gene Ther 13:1027–1036PubMedCrossRefGoogle Scholar
  110. 110.
    Miyahira Y, Murata K, Rodriguez D, Rodriguez JR, Esteban M, Rodrigues MM, Zavala F (1995) Quantification of antigen specific CD8+ T cells using an ELISPOT assay. J Immunol Methods 181:45–54PubMedCrossRefGoogle Scholar
  111. 111.
    Mohamadzadeh M, Berard F, Essert G, Chalouni C, Pulendran B, Davoust J, Bridges G, Palucka AK, Banchereau J (2001) Interleukin 15 skews monocyte differentiation into dendritic cells with features of Langerhans cells. J Exp Med 194:1013–1020PubMedCrossRefGoogle Scholar
  112. 112.
    Mohty M, Jarrossay D, Lafage-Pochitaloff M, Zandotti C, Briere F, de Lamballeri XN, Isnardon D, Sainty D, Olive D, Gaugler B (2001) Circulating blood dendritic cells from myeloid leukemia patients display quantitative and cytogenetic abnormalities as well as functional impairment. Blood 98:3750–3756PubMedCrossRefGoogle Scholar
  113. 113.
    Mohty M, Vialle-Castellano A, Nunes JA, Isnardon D, Olive D, Gaugler B (2003) IFN-alpha skews monocyte differentiation into Toll-like receptor 7-expressing dendritic cells with potent functional activities. J Immunol 171:3385–3393PubMedGoogle Scholar
  114. 114.
    Muller AJ, Scherle PA (2006) Targeting the mechanisms of tumoral immune tolerance with small-molecule inhibitors. Nat Rev Cancer 6:613–625PubMedCrossRefGoogle Scholar
  115. 115.
    Mullins DW, Sheasley SL, Ream RM, Bullock TN, Fu YX, Engelhard VH (2003) Route of immunization with peptide-pulsed dendritic cells controls the distribution of memory and effector T cells in lymphoid tissues and determines the pattern of regional tumor control. J Exp Med 198:1023–1034PubMedCrossRefGoogle Scholar
  116. 116.
    Munn DH, Sharma MD, Lee JR, Jhaver KG, Johnson TS, Keskin DB, Marshall B, Chandler P, Antonia SJ, Burgess R, Slingluff CL Jr, Mellor AL (2002) Potential regulatory function of human dendritic cells expressing indoleamine 2,3-dioxygenase. Science 297:1867–1870PubMedCrossRefGoogle Scholar
  117. 117.
    Nair S, McLaughlin C, Weizer A, Su Z, Boczkowski D, Dannull J, Vieweg J, Gilboa E (2003) Injection of immature dendritic cells into adjuvant-treated skin obviates the need for ex vivo maturation. J Immunol 171:6275–6282PubMedGoogle Scholar
  118. 118.
    Nair SK, Morse M, Boczkowski D, Cumming RI, Vasovic L, Gilboa E, Lyerly HK (2002) Induction of tumor-specific cytotoxic T lymphocytes in cancer patients by autologous tumor RNA-transfected dendritic cells. Ann Surg 235:540–549PubMedCrossRefGoogle Scholar
  119. 119.
    Novellino L, Castelli C, Parmiani G (2005) A listing of human tumor antigens recognized by T cells: March 2004 update. Cancer Immunol Immunother 54:187–207PubMedCrossRefGoogle Scholar
  120. 120.
    Nowrousian MR, Waschke S, Bojko P, Welt A, Schuett P, Ebeling P, Flasshove M, Moritz T, Schuette J, Seeber S (2003) Impact of chemotherapy regimen and hematopoietic growth factor on mobilization and collection of peripheral blood stem cells in cancer patients. Ann Oncol 14(suppl 1):i29–i36PubMedCrossRefGoogle Scholar
  121. 121.
    Obermaier B, Dauer M, Herten J, Schad K, Endres S, Eigler A (2003) Development of a new protocol for 2-day generation of mature dendritic cells from human monocytes. Biol Proced Online 5:197–203PubMedCrossRefGoogle Scholar
  122. 122.
    O’Neill DW, Adams S, Bhardwaj N (2004) Manipulating dendritic cell biology for the active immunotherapy of cancer. Blood 104:2235–2246PubMedCrossRefGoogle Scholar
  123. 123.
    O’Rourke MG, Johnson M, Lanagan C, See J, Yang J, Bell JR, Slater GJ, Kerr BM, Crowe B, Purdie DM, Elliott SL, Ellem KA, Schmidt CW (2003) Durable complete clinical responses in a phase I/II trial using an autologous melanoma cell/dendritic cell vaccine. Cancer Immunol Immunother 52:387–395PubMedGoogle Scholar
  124. 124.
    Orsini E, Guarini A, Chiaretti S, Mauro FR, Foa R (2003) The circulating dendritic cell compartment in patients with chronic lymphocytic leukemia is severely defective and unable to stimulate an effective T-cell response. Cancer Res 63:4497–4506PubMedGoogle Scholar
  125. 125.
    Orsini E, Pasquale A, Maggio R, Calabrese E, Mauro FR, Giammartini E, Guarini A, Foa R (2004) Phenotypic and functional characterization of monocyte-derived dendritic cells in chronic lymphocytic leukaemia patients: influence of neoplastic CD19 cells in vivo and in vitro. Br J Haematol 125:720–728PubMedCrossRefGoogle Scholar
  126. 126.
    Osugi Y, Vuckovic S, Hart DN (2002) Myeloid blood CD11c(+) dendritic cells and monocyte-derived dendritic cells differ in their ability to stimulate T lymphocytes. Blood 100:2858–2866PubMedCrossRefGoogle Scholar
  127. 127.
    Palmowski MJ, Choi EM, Hermans IF, Gilbert SC, Chen JL, Gileadi U, Salio M, Van Pel A, Man S, Bonin E, Liljestrom P, Dunbar PR, Cerundolo V (2002) Competition between CTL narrows the immune response induced by prime-boost vaccination protocols. J Immunol 168:4391–4398PubMedGoogle Scholar
  128. 128.
    Pandolfino MC, Viret C, Gervois N, Guilloux Y, Davodeau F, Diez E, Jotereau F (1992) Specificity, T cell receptor diversity and activation requirements of CD4+ and CD8+ clones derived from human melanoma-infiltrating lymphocytes. Eur J Immunol 22:1795–1802PubMedCrossRefGoogle Scholar
  129. 129.
    Pardoll D (2003) Does the immune system see tumors as foreign or self? Annu Rev Immunol 21:807–839PubMedCrossRefGoogle Scholar
  130. 130.
    Parkhurst MR, Salgaller ML, Southwood S, Robbins PF, Sette A, Rosenberg SA, Kawakami Y (1996) Improved induction of melanoma-reactive CTL with peptides from the melanoma antigen gp100 modified at HLA-A*0201-binding residues. J Immunol 157:2539–2548PubMedGoogle Scholar
  131. 131.
    Parlato S, Santini SM, Lapenta C, Di Pucchio T, Logozzi M, Spada M, Giammarioli AM, Malorni W, Fais S, Belardelli F (2001) Expression of CCR-7, MIP-3beta, and Th-1 chemokines in type I IFN-induced monocyte-derived dendritic cells: importance for the rapid acquisition of potent migratory and functional activities. Blood 98:3022–3029PubMedCrossRefGoogle Scholar
  132. 132.
    Pedersen AE, Thorn M, Gad M, Walter MR, Johnsen HE, Gaarsdal E, Nikolajsen K, Buus S, Claesson MH, Svane IM (2005) Phenotypic and functional characterization of clinical grade dendritic cells generated from patients with advanced breast cancer for therapeutic vaccination. Scand J Immunol 61:147–156PubMedCrossRefGoogle Scholar
  133. 133.
    Ponsaerts P, Van den Bosch G, Cools N, Van Driessche A, Nijs G, Lenjou M, Lardon F, Van Broeckhoven C, Van Bockstaele DR, Berneman ZN, Van Tendeloo VF (2002) Messenger RNA electroporation of human monocytes, followed by rapid in vitro differentiation, leads to highly stimulatory antigen-loaded mature dendritic cells. J Immunol 169:1669–1675PubMedGoogle Scholar
  134. 134.
    Powell DJ Jr, Rosenberg SA (2004) Phenotypic and functional maturation of tumor antigen-reactive CD8+ T lymphocytes in patients undergoing multiple course peptide vaccination. J Immunother 27:36–47PubMedCrossRefGoogle Scholar
  135. 135.
    Pullarkat V, Lau R, Lee SM, Bender JG, Weber JS (2002) Large-scale monocyte enrichment coupled with a closed culture system for the generation of human dendritic cells. J Immunol Methods 267:173–183PubMedCrossRefGoogle Scholar
  136. 136.
    Radvanyi LG, Banerjee A, Weir M, Messner H (1999) Low levels of interferon-alpha induce CD86 (B7.2) expression and accelerates dendritic cell maturation from human peripheral blood mononuclear cells. Scand J Immunol 50:499–509PubMedCrossRefGoogle Scholar
  137. 137.
    Ramakrishna V, Treml JF, Vitale L, Connolly JE, O’Neill T, Smith PA, Jones CL, He LZ, Goldstein J, Wallace PK, Keler T, Endres MJ (2004) Mannose receptor targeting of tumor antigen pmel17 to human dendritic cells directs anti-melanoma T cell responses via multiple HLA molecules. J Immunol 172:2845–2852PubMedGoogle Scholar
  138. 138.
    Randolph GJ, Beaulieu S, Lebecque S, Steinman RM, Muller WA (1998) Differentiation of monocytes into dendritic cells in a model of transendothelial trafficking. Science 282:480–483PubMedCrossRefGoogle Scholar
  139. 139.
    Ratta M, Fagnoni F, Curti A, Vescovini R, Sansoni P, Oliviero B, Fogli M, Ferri E, Della Cuna GR, Tura S, Baccarani M, Lemoli RM (2002) Dendritic cells are functionally defective in multiple myeloma: the role of interleukin-6. Blood 100:230–237PubMedCrossRefGoogle Scholar
  140. 140.
    Reichardt VL, Brossart P, Kanz L (2004) Dendritic cells in vaccination therapies of human malignant disease. Blood Rev 18:235–243PubMedCrossRefGoogle Scholar
  141. 141.
    Reis e Sousa C (2006) Dendritic cells in a mature age. Nat Rev Immunol 6:476–483PubMedCrossRefGoogle Scholar
  142. 142.
    Renneson J, Salio M, Mazouz N, Goldman M, Marchant A, Cerundolo V (2005) Mature dendritic cells differentiated in the presence of interferon-beta and interleukin-3 prime functional antigen-specific CD8 T cells. Clin Exp Immunol 139:468–475PubMedCrossRefGoogle Scholar
  143. 143.
    Ribas A, Glaspy JA, Lee Y, Dissette VB, Seja E, Vu HT, Tchekmedyian NS, Oseguera D, Comin-Anduix B, Wargo JA, Amarnani SN, McBride WH, Economou JS, Butterfield LH (2004) Role of dendritic cell phenotype, determinant spreading, and negative costimulatory blockade in dendritic cell-based melanoma immunotherapy. J Immunother 27:354–367PubMedCrossRefGoogle Scholar
  144. 144.
    Robinson SP, Patterson S, English N, Davies D, Knight SC, Reid CD (1999) Human peripheral blood contains two distinct lineages of dendritic cells. Eur J Immunol 29:2769–2778PubMedCrossRefGoogle Scholar
  145. 145.
    Romani N, Reider D, Heuer M, Ebner S, Kampgen E, Eibl B, Niederwieser D, Schuler G (1996) Generation of mature dendritic cells from human blood. An improved method with special regard to clinical applicability. J Immunol Methods 196:137–151PubMedCrossRefGoogle Scholar
  146. 146.
    Rosenberg SA, Yang JC, Restifo NP (2004) Cancer immunotherapy: moving beyond current vaccines. Nat Med 10:909–915PubMedCrossRefGoogle Scholar
  147. 147.
    Rosenblatt J, Kufe D, Avigan D (2005) Dendritic cell fusion vaccines for cancer immunotherapy. Expert Opin Biol Ther 5:703–715PubMedCrossRefGoogle Scholar
  148. 148.
    Rossi M, Young JW (2005) Human dendritic cells: potent antigen-presenting cells at the crossroads of innate and adaptive immunity. J Immunol 175:1373–1381PubMedGoogle Scholar
  149. 149.
    Rouard H, Leon A, De Reys S, Taylor L, Logan J, Marquet J, Jouault H, Loper K, Maison P, Delfau-Larue MH, Beaujean F, Farcet JP, Noga SJ (2003) A closed and single-use system for monocyte enrichment: potential for dendritic cell generation for clinical applications. Transfusion 43:481–487PubMedCrossRefGoogle Scholar
  150. 150.
    Russell NH, McQuaker G, Stainer C, Byrne JL, Haynes AP (1998) Stem cell mobilisation in lymphoproliferative diseases. Bone Marrow Transplant 22:935–940PubMedCrossRefGoogle Scholar
  151. 151.
    Rutella S, Danese S, Leone G (2006) Tolerogenic dendritic cells: cytokine modulation comes of age. Blood 108:1435–1440PubMedCrossRefGoogle Scholar
  152. 152.
    Sakakibara M, Kanto T, Inoue M, Kaimori A, Yakushijin T, Miyatake H, Itose I, Miyazaki M, Kuzushita N, Hiramatsu N, Takehara T, Kasahara A, Hayashi N (2006) Quick generation of fully mature dendritic cells from monocytes with OK432, low-dose prostanoid, and interferon-alpha as potent immune enhancers. J Immunother 29:67–77PubMedCrossRefGoogle Scholar
  153. 153.
    Santini SM, Di Pucchio T, Lapenta C, Parlato S, Logozzi M, Belardelli F (2003) A new type I IFN-mediated pathway for the rapid differentiation of monocytes into highly active dendritic cells. Stem Cells 21:357–362PubMedCrossRefGoogle Scholar
  154. 154.
    Santini SM, Lapenta C, Logozzi M, Parlato S, Spada M, Di Pucchio T, Belardelli F (2000) Type I interferon as a powerful adjuvant for monocyte-derived dendritic cell development and activity in vitro and in Hu-PBL-SCID mice. J Exp Med 191:1777–1788PubMedCrossRefGoogle Scholar
  155. 155.
    Sauter B, Albert ML, Francisco L, Larsson M, Somersan S, Bhardwaj N (2000) Consequences of cell death: exposure to necrotic tumor cells, but not primary tissue cells or apoptotic cells, induces the maturation of immunostimulatory dendritic cells. J Exp Med 191:423–434PubMedCrossRefGoogle Scholar
  156. 156.
    Savary CA, Grazziutti ML, Melichar B, Przepiorka D, Freedman RS, Cowart RE, Cohen DM, Anaissie EJ, Woodside DG, McIntyre BW, Pierson DL, Pellis NR, Rex JH (1998) Multidimensional flow-cytometric analysis of dendritic cells in peripheral blood of normal donors and cancer patients. Cancer Immunol Immunother 45:234–240PubMedCrossRefGoogle Scholar
  157. 157.
    Schrama D, Fuchs E, Brocker EB, Thor Straten P, Becker JC (2002) Identical T-cell receptor transcripts in multiple melanoma metastases. Cancer Res 62:5664–5667PubMedGoogle Scholar
  158. 158.
    Schuler G, Schuler-Thurner B, Steinman RM (2003) The use of dendritic cells in cancer immunotherapy. Curr Opin Immunol 15:138–147PubMedCrossRefGoogle Scholar
  159. 159.
    Schutt P, Buttkereit U, Brandhorst D, Lindemann M, Schmiedl S, Grosse-Wilde H, Seeber S, Nowrousian MR, Opalka B, Moritz T (2005) In vitro dendritic cell generation and lymphocyte subsets in myeloma patients: influence of thalidomide and high-dose chemotherapy treatment. Cancer Immunol Immunother 54:506–512PubMedCrossRefGoogle Scholar
  160. 160.
    Schuurhuis DH, van Montfoort N, Ioan-Facsinay A, Jiawan R, Camps M, Nouta J, Melief CJ, Verbeek JS, Ossendorp F (2006) Immune complex-loaded dendritic cells are superior to soluble immune complexes as antitumor vaccine. J Immunol 176:4573–4580PubMedGoogle Scholar
  161. 161.
    Seddiki N, Santner-Nanan B, Martinson J, Zaunders J, Sasson S, Landay A, Solomon M, Selby W, Alexander SI, Nanan R, Kelleher A, Fazekas de St Groth B (2006) Expression of interleukin (IL)-2 and IL-7 receptors discriminates between human regulatory and activated T cells. J Exp Med 203:1693–1700PubMedCrossRefGoogle Scholar
  162. 162.
    Siena S, Di Nicola M, Bregni M, Mortarini R, Anichini A, Lombardi L, Ravagnani F, Parmiani G, Gianni AM (1995) Massive ex vivo generation of functional dendritic cells from mobilized CD34+ blood progenitors for anticancer therapy. Exp Hematol 23:1463–1471PubMedGoogle Scholar
  163. 163.
    Smith CM, Wilson NS, Waithman J, Villadangos JA, Carbone FR, Heath WR, Belz GT (2004) Cognate CD4(+) T cell licensing of dendritic cells in CD8(+) T cell immunity. Nat Immunol 5:1143–1148PubMedCrossRefGoogle Scholar
  164. 164.
    Snyder JE, Bowers WJ, Livingstone AM, Lee FE, Federoff HJ, Mosmann TR (2003) Measuring the frequency of mouse and human cytotoxic T cells by the Lysispot assay: independent regulation of cytokine secretion and short-term killing. Nat Med 9:231–235PubMedCrossRefGoogle Scholar
  165. 165.
    Speiser DE, Lienard D, Pittet MJ, Batard P, Rimoldi D, Guillaume P, Cerottini JC, Romero P (2002) In vivo activation of melanoma-specific CD8(+) T cells by endogenous tumor antigen and peptide vaccines. A comparison to virus-specific T cells. Eur J Immunol 32:731–741PubMedCrossRefGoogle Scholar
  166. 166.
    Spisek R, Brazova J, Rozkova D, Zapletalova K, Sediva A, Bartunkova J (2004) Maturation of dendritic cells by bacterial immunomodulators. Vaccine 22:2761–2768PubMedCrossRefGoogle Scholar
  167. 167.
    Spisek R, Bretaudeau L, Barbieux I, Meflah K, Gregoire M (2001) Standardized generation of fully mature p70 IL-12 secreting monocyte-derived dendritic cells for clinical use. Cancer Immunol Immunother 50:417–427PubMedCrossRefGoogle Scholar
  168. 168.
    Steinbrink K, Wolfl M, Jonuleit H, Knop J, Enk AH (1997) Induction of tolerance by IL-10-treated dendritic cells. J Immunol 159:4772–4780PubMedGoogle Scholar
  169. 169.
    Steinman RM (2003) Some interfaces of dendritic cell biology. APMIS 111:675–697PubMedCrossRefGoogle Scholar
  170. 170.
    Stuge TB, Holmes SP, Saharan S, Tuettenberg A, Roederer M, Weber JS, Lee PP (2004) Diversity and recognition efficiency of T cell responses to cancer. PLoS Med 1:e28PubMedCrossRefGoogle Scholar
  171. 171.
    Su Z, Dannull J, Yang BK, Dahm P, Coleman D, Yancey D, Sichi S, Niedzwiecki D, Boczkowski D, Gilboa E, Vieweg J (2005) Telomerase mRNA-transfected dendritic cells stimulate antigen-specific CD8+ and CD4+ T cell responses in patients with metastatic prostate cancer. J Immunol 174:3798–3807PubMedGoogle Scholar
  172. 172.
    Suen Y, Lee SM, Aono F, Hou S, Loudovaris M, Ofstein G, Bender JG (2001) Comparison of monocyte enrichment by immuno-magnetic depletion or adherence for the clinical-scale generation of DC. Cytotherapy 3:365–375PubMedCrossRefGoogle Scholar
  173. 173.
    Suni MA, Picker LJ, Maino VC (1998) Detection of antigen-specific T cell cytokine expression in whole blood by flow cytometry. J Immunol Methods 212:89–98PubMedCrossRefGoogle Scholar
  174. 174.
    Syme R, Bajwa R, Robertson L, Stewart D, Gluck S (2005) Comparison of CD34 and monocyte-derived dendritic cells from mobilized peripheral blood from cancer patients. Stem Cells 23:74–81PubMedCrossRefGoogle Scholar
  175. 175.
    Tacken PJ, de Vries IJ, Gijzen K, Joosten B, Wu D, Rother RP, Faas SJ, Punt CJ, Torensma R, Adema GJ, Figdor CG (2005) Effective induction of naive and recall T-cell responses by targeting antigen to human dendritic cells via a humanized anti-DC-SIGN antibody. Blood 106:1278–1285PubMedCrossRefGoogle Scholar
  176. 176.
    Tamir A, Jordan WJ, Ritter M, Habib N, Lechler RI, Foster GR, Lombardi G (2005) Interferon-alpha2a is sufficient for promoting dendritic cell immunogenicity. Clin Exp Immunol 142:471–480PubMedGoogle Scholar
  177. 177.
    Tassignon J, Burny W, Dahmani S, Zhou L, Stordeur P, Byl B, De Groote D (2005) Monitoring of cellular responses after vaccination against tetanus toxoid: comparison of the measurement of IFN-gamma production by ELISA, ELISPOT, flow cytometry and real-time PCR. J Immunol Methods 305:188–198PubMedCrossRefGoogle Scholar
  178. 178.
    Ten Brinke A, Karsten ML, Dieker MC, Zwaginga JJ, Vrielink H, Marieke van Ham S (2006) Generation of dendritic cells for immunotherapy is minimally impaired by granulocytes in the monocyte preparation. Immunobiology 211:633–640PubMedCrossRefGoogle Scholar
  179. 179.
    Thomas R, Lipsky PE (1994) Human peripheral blood dendritic cell subsets. Isolation and characterization of precursor and mature antigen-presenting cells. J Immunol 153:4016–4028PubMedGoogle Scholar
  180. 180.
    Thurnher M, Zelle-Rieser C, Ramoner R, Bartsch G, Holtl L (2001) The disabled dendritic cell. FASEB J 15:1054–1061PubMedCrossRefGoogle Scholar
  181. 181.
    Tkachenko N, Wojas K, Tabarkiewicz J, Rolinski J (2005) Generation of dendritic cells from human peripheral blood monocytes-comparison of different culture media. Folia Histochem Cytobiol 43:25–30PubMedGoogle Scholar
  182. 182.
    Tosi D, Valenti R, Cova A, Sovena G, Huber V, Pilla L, Arienti F, Belardelli F, Parmiani G, Rivoltini L (2004) Role of cross-talk between IFN-alpha-induced monocyte-derived dendritic cells and NK cells in priming CD8+ T cell responses against human tumor antigens. J Immunol 172:5363–5370PubMedGoogle Scholar
  183. 183.
    Toungouz M, Quinet C, Thille E, Fourez S, Pradier O, Delville JP, Velu T, Lambermont M (1999) Generation of immature autologous clinical grade dendritic cells for vaccination of cancer patients. Cytotherapy 1:447–453CrossRefGoogle Scholar
  184. 184.
    Trakatelli M, Toungouz M, Blocklet D, Dodoo Y, Gordower L, Laporte M, Vereecken P, Sales F, Mortier L, Mazouz N, Lambermont M, Goldman S, Coulie P, Goldman M, Velu T (2006) A new dendritic cell vaccine generated with interleukin-3 and interferon-beta induces CD8+ T cell responses against NA17-A2 tumor peptide in melanoma patients. Cancer Immunol Immunother 55:469–474PubMedCrossRefGoogle Scholar
  185. 185.
    Trefzer U, Herberth G, Wohlan K, Milling A, Thiemann M, Sharav T, Sparbier K, Sterry W, Walden P (2005) Tumour-dendritic hybrid cell vaccination for the treatment of patients with malignant melanoma: immunological effects and clinical results. Vaccine 23:2367–2373PubMedCrossRefGoogle Scholar
  186. 186.
    Trefzer U, Herberth G, Wohlan K, Milling A, Thiemann M, Sherev T, Sparbier K, Sterry W, Walden P (2004) Vaccination with hybrids of tumor and dendritic cells induces tumor-specific T-cell and clinical responses in melanoma stage III and IV patients. Int J Cancer 110:730–740PubMedCrossRefGoogle Scholar
  187. 187.
    Tuettenberg A, Becker C, Huter E, Knop J, Enk AH, Jonuleit H (2006) Induction of strong and persistent MelanA/MART-1-specific immune responses by adjuvant dendritic cell-based vaccination of stage II melanoma patients. Int J Cancer 118:2617–2627PubMedCrossRefGoogle Scholar
  188. 188.
    Tuyaerts S, Michiels A, Corthals J, Bonehill A, Heirman C, de Greef C, Noppe SM, Thielemans K (2003) Induction of Influenza Matrix Protein 1 and MelanA-specific T lymphocytes in vitro using mRNA-electroporated dendritic cells. Cancer Gene Ther 10:696–706PubMedCrossRefGoogle Scholar
  189. 189.
    Tuyaerts S, Noppe SM, Corthals J, Breckpot K, Heirman C, De Greef C, Van Riet I, Thielemans K (2002) Generation of large numbers of dendritic cells in a closed system using Cell Factories. J Immunol Methods 264:135–151PubMedCrossRefGoogle Scholar
  190. 190.
    Van Tendeloo VF, Ponsaerts P, Lardon F, Nijs G, Lenjou M, Van Broeckhoven C, Van Bockstaele DR, Berneman ZN (2001) Highly efficient gene delivery by mRNA electroporation in human hematopoietic cells: superiority to lipofection and passive pulsing of mRNA and to electroporation of plasmid cDNA for tumor antigen loading of dendritic cells. Blood 98:49–56PubMedCrossRefGoogle Scholar
  191. 191.
    Van Tendeloo VF, Snoeck HW, Lardon F, Vanham GL, Nijs G, Lenjou M, Hendriks L, Van Broeckhoven C, Moulijn A, Rodrigus I, Verdonk P, Van Bockstaele DR, Berneman ZN (1998) Nonviral transfection of distinct types of human dendritic cells: high-efficiency gene transfer by electroporation into hematopoietic progenitor- but not monocyte-derived dendritic cells. Gene Ther 5:700–707PubMedCrossRefGoogle Scholar
  192. 192.
    Vanderlugt CL, Miller SD (2002) Epitope spreading in immune-mediated diseases: implications for immunotherapy. Nat Rev Immunol 2:85–95PubMedCrossRefGoogle Scholar
  193. 193.
    Vari F, Hart DN (2004) Loading DCs with Ag. Cytotherapy 6:111–121PubMedGoogle Scholar
  194. 194.
    Velders MP, Markiewicz MA, Eiben GL, Kast WM (2003) CD4+ T cell matters in tumor immunity. Int Rev Immunol 22:113–140PubMedCrossRefGoogle Scholar
  195. 195.
    Westermann J, Lessen A, Schlimper C, Baskaynak G, le Coutre P, Dorken B, Pezzutto A (2006) Simultaneous cytokine analysis by cytometric bead array for the detection of leukaemia-reactive T cells in patients with chronic myeloid leukaemia. Br J Haematol 132:32–35PubMedCrossRefGoogle Scholar
  196. 196.
    Whiteside TL, Zhao Y, Tsukishiro T, Elder EM, Gooding W, Baar J (2003) Enzyme-linked immunospot, cytokine flow cytometry, and tetramers in the detection of T-cell responses to a dendritic cell-based multipeptide vaccine in patients with melanoma. Clin Cancer Res 9:641–649PubMedGoogle Scholar
  197. 197.
    Wong EC, Lee SM, Hines K, Lee J, Carter CS, Kopp W, Bender J, Read EJ (2002) Development of a closed-system process for clinical-scale generation of DCs: evaluation of two monocyte-enrichment methods and two culture containers. Cytotherapy 4:65–76PubMedCrossRefGoogle Scholar
  198. 198.
    Xu S, Koski GK, Faries M, Bedrosian I, Mick R, Maeurer M, Cheever MA, Cohen PA, Czerniecki BJ (2003) Rapid high efficiency sensitization of CD8+ T cells to tumor antigens by dendritic cells leads to enhanced functional avidity and direct tumor recognition through an IL-12-dependent mechanism. J Immunol 171:2251–2261PubMedGoogle Scholar
  199. 199.
    Yamanaka R, Homma J, Yajima N, Tsuchiya N, Sano M, Kobayashi T, Yoshida S, Abe T, Narita M, Takahashi M, Tanaka R (2005) Clinical evaluation of dendritic cell vaccination for patients with recurrent glioma: results of a clinical phase I/II trial. Clin Cancer Res 11:4160–4167PubMedCrossRefGoogle Scholar
  200. 200.
    Yang L, Carbone DP (2004) Tumor-host immune interactions and dendritic cell dysfunction. Adv Cancer Res 92:13–27PubMedCrossRefGoogle Scholar
  201. 201.
    Yannelli JR, Sturgill J, Foody T, Hirschowitz E (2005) The large scale generation of dendritic cells for the immunization of patients with non-small cell lung cancer (NSCLC). Lung Cancer 47:337–350PubMedCrossRefGoogle Scholar
  202. 202.
    Yannelli JR, Wroblewski JM (2004) On the road to a tumor cell vaccine: 20 years of cellular immunotherapy. Vaccine 23:97–113PubMedCrossRefGoogle Scholar
  203. 203.
    Yoshida S, Yamamoto K, Tanaka R (2003) Generation of dendritic cells from the ventricular fluid in patients with meningeal carcinomatosis. J Neuroimmunol 140:172–176PubMedCrossRefGoogle Scholar
  204. 204.
    Zeng G, Li Y, El-Gamil M, Sidney J, Sette A, Wang RF, Rosenberg SA, Robbins PF (2002) Generation of NY-ESO-1-specific CD4+ and CD8+ T cells by a single peptide with dual MHC class I and class II specificities: a new strategy for vaccine design. Cancer Res 62:3630–3635PubMedGoogle Scholar
  205. 205.
    Zitvogel L, Tesniere A, Kroemer G (2006) Cancer despite immunosurveillance: immunoselection and immunosubversion. Nat Rev Immunol 6:715–727PubMedCrossRefGoogle Scholar
  206. 206.
    Zwaveling S, Ferreira Mota SC, Nouta J, Johnson M, Lipford GB, Offringa R, van der Burg SH, Melief CJ (2002) Established human papillomavirus type 16-expressing tumors are effectively eradicated following vaccination with long peptides. J Immunol 169:350–358PubMedGoogle Scholar

Copyright information

© Springer-Verlag 2007

Authors and Affiliations

  • Sandra Tuyaerts
    • 1
  • Joeri L. Aerts
    • 1
  • Jurgen Corthals
    • 1
  • Bart Neyns
    • 2
  • Carlo Heirman
    • 1
  • Karine Breckpot
    • 1
  • Kris Thielemans
    • 1
  • Aude Bonehill
    • 1
  1. 1.Laboratory of Molecular and Cellular Therapy, Department of Physiology and ImmunologyMedical School of the Vrije Universiteit BrusselBrusselsBelgium
  2. 2.Medical Oncology, Oncology Center, University Hospital BrusselsFree University BrusselsBrusselsBelgium

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