Skip to main content
SpringerLink
Log in

Dendritic Cell-Based Immunotherapy in Myeloid Leukaemia: Translating Fundamental Mechanisms into Clinical Applications

  • Chapter
Dendritic Cells

Part of the book series: Handbook of Experimental Pharmacology ((HEP,volume 188))

Abstract

Immunotherapy for leukaemia patients, aiming at the generation of anti-leukaemic T cell responses, could provide a new therapeutic approach to eliminate minimal residual disease (MRD) cells in acute myeloid leukaemia (AML). Leukaemic blasts harbour several ways to escape the immune system including deficient MHC class II expression, low levels of co-stimulatory molecules and suppres-sive cytokines. Therapeutic vaccination with dendritic cells (DC) is now recognized as an important investigational therapy. Due to their unique antigen presenting capacity, immunosuppressive features of the leukaemic blasts can be circumvented. DC can be successfully cultured from leukaemic blasts in 60–70% of patients and show functional potential in vivo. Alternatively, monocyte derived DC obtained at time of complete remission loaded with leukaemia-specific antigens can be used as vaccine. Several sources of leukaemia-associated antigen and different methods of loading antigen onto DC have been used in an attempt to optimize antitumour responses including apoptotic cells, necrotic cell lysates and tumour-associated pep-tides. Currently, the AML-derived cell line MUTZ-3, an immortalized equivalent of CD34+ DC precursor cells, is under investigation for vaccination purposes. For effective DC vaccination the intrinsic tolerant state of the patient must be overcome. Therefore, the development of efficient and safe adjuvants in antigen specific im-munotherapeutic programs should be encouraged.

This is a preview of subscription content, log in via an institution to check access.

Access this chapter

Log in via an institution
Chapter
USD 29.95
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
eBook
USD 259.00
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
Softcover Book
USD 329.99
Price excludes VAT (USA)
  • Compact, lightweight edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info
Hardcover Book
USD 329.99
Price excludes VAT (USA)
  • Durable hardcover edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info

Tax calculation will be finalised at checkout

Purchases are for personal use only

Institutional subscriptions

Preview

Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.

References

  • Ackerman AL, Cresswell P (2004) Cellular mechanisms governing cross-presentation of exogenous antigens. Nat Immunol 5:678–684

    PubMed  CAS  Google Scholar 

  • Amigorena S (2002) Fc gamma receptors and cross-presentation in dendritic cells. J Exp Med 195:F1–F3

    PubMed  CAS  Google Scholar 

  • Amoscato AA, Prenovitz DA, Lotze MT (1998) Rapid extracellular degradation of synthetic class I peptides by human dendritic cells. J Immunol 161:4023–4032

    PubMed  CAS  Google Scholar 

  • Andres PG, Howland KC, Dresnek D, Edmondson S, Abbas AK, Krummel MF (2004) CD28 signals in the immature immunological synapse. J Immunol 172:5880–5886

    PubMed  CAS  Google Scholar 

  • Armstrong TD, Clements VK, Martin BK, Ting JP, Ostrand-Rosenberg S (1997) Major histocom-patibility complex class II-transfected tumor cells present endogenous antigen and are potent inducers of tumor-specific immunity. Proc Natl Acad Sci USA 94:6886–6891

    PubMed  CAS  Google Scholar 

  • Banchereau J, Steinman RM (1998) Dendritic cells and the control of immunity. Nature 392: 245–252

    PubMed  CAS  Google Scholar 

  • Banchereau J, Briere F, Caux C, Davoust J, Lebecque S, Liu YJ, Pulendran B, Palucka K (2000) Immunobiology of dendritic cells. Annu Rev Immunol 18:767–811

    PubMed  CAS  Google Scholar 

  • 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 21:3826–3835

    PubMed  CAS  Google Scholar 

  • Blachere NE, Darnell RB, Albert ML (2005) Apoptotic cells deliver processed antigen to dendritic cells for cross-presentation. PLoS Biol 3:1070–1086

    CAS  Google Scholar 

  • Blander JM, Medzhitov R (2006) On regulation of phagosome maturation and antigen presentation. Nat Immunol 7:1029–1035

    PubMed  CAS  Google Scholar 

  • Bramson JL, Hitt M, Addison CL, Muller WJ, Gauldie J, Graham FL (1996) Direct intratumoral injection of an adenovirus expressing interleukin-12 induces regression and long-lasting immunity that is associated with highly localized expression of interleukin-12. Hum Gene Ther 7:1995–2002

    PubMed  CAS  Google Scholar 

  • Bromley SK, Iaboni A, Davis SJ, Whitty A, Green JM, Shaw AS, Weiss A, Dustin ML (2001) The immunological synapse and CD28-CD80 interactions. Nat Immunol 2:1159–1166

    PubMed  CAS  Google Scholar 

  • 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 96:3102–3108

    PubMed  CAS  Google Scholar 

  • Brossart P, Schneider A, Dill P, Schammann T, Grunebach F, Wirths S, Kanz L, Buhring HJ, Brug-ger W (2001) The epithelial tumor antigen MUC1 is expressed in hematological malignancies and is recognized by MUC1-specific cytotoxic T-lymphocytes. Cancer Res 61:6846–6850

    PubMed  CAS  Google Scholar 

  • Brouwer RE, van der Hoorn MA, Kluin-Nelemans HC, van Zelderen-BholaS, Willemze R, Falken-burg JH (2000a) The generation of dendritic-like cells with increased allostimulatory function from acute myeloid leukemia cells of various FAB subclasses. Hum Immunol 61:565–574

    CAS  Google Scholar 

  • Brouwer RE, Zwinderman KH, Kluin-Nelemans HC, van Luxemburg-Heijs SA, Willemze R, Falkenburg JH (2000b) Expression and induction of costimulatory and adhesion molecules on acute myeloid leukemic cells: implications for adoptive immunotherapy. Exp Hematol 28: 161–168

    CAS  Google Scholar 

  • Brown JA, Dorfman DM, Ma FR, Sullivan EL, Munoz O, Wood CR, Greenfield EA, Freeman GJ (2003) Blockade of programmed death-1 ligands on dendritic cells enhances T cell activation and cytokine production. J Immunol 170:1257–1266

    PubMed  CAS  Google Scholar 

  • Buggins AG, Lea N, Gaken J, Darling D, Farzaneh F, Mufti GJ, Hirst WJ (1999) Effect of costim-ulation and the microenvironment on antigen presentation by leukemic cells. Blood 94:3479– 3490

    PubMed  CAS  Google Scholar 

  • Buggins AG, Milojkovic D, Arno MJ, Lea NC, Mufti GJ, Thomas NS, Hirst WJ (2001) Microenvi-ronment produced by acute myeloid leukemia cells prevents T cell activation and proliferation by inhibition of NF-kappaB, c-Myc, and pRb pathways. J Immunol 167:6021–6030

    PubMed  CAS  Google Scholar 

  • 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 9:998–1008

    PubMed  CAS  Google Scholar 

  • Camporeale A, Boni A, Iezzi G, Degl'Innocenti E, Grioni M, Mondino A, Bellone M (2003) Critical impact of the kinetics of dendritic cells activation on the in vivo induction of tumor-specific T lymphocytes. Cancer Res 63:3688–3694

    PubMed  CAS  Google Scholar 

  • Caux C, Massacrier C, Vanbervliet B, Dubois B, de Saint-Vis B, zutter-Dambuyant C, Jacquet C, Schmitt D, Banchereau J (1997) CD34+ hematopoietic progenitors from human cord blood differentiate along two independent dendritic cell pathways in response to GM — CSF +TNF alpha. Adv Exp Med Biol 417:21–25

    PubMed  CAS  Google Scholar 

  • Cella M, Scheidegger D, Palmer-Lehmann K, Lane P, Lanzavecchia A, Alber G (1996) Ligation of CD40 on dendritic cells triggers production of high levels of interleukin-12 and enhances T cell stimulatory capacity: T-T help via APC activation. J Exp Med 184:747–752

    PubMed  CAS  Google Scholar 

  • Chalouni C, Banchereau J, Vogt AB, Pascual V, Davoust J (2003) Human germinal center B cells differ from naive and memory B cells by their aggregated MHC class II-rich compartments lacking HLA-DO. Int Immunol 15:457–466

    PubMed  CAS  Google Scholar 

  • Chamuleau FN, Kelder A, van de Loosdrecht AA, Ossenkoppele GJ (2006) High CLIP (Class II Associated Invariant Chain Peptide) Expression on Minimal Residual Disease Cells Is Associated with High Relapse Rate in AML Patients. 108: Abstract 2300

    Google Scholar 

  • Chamuleau ME, Souwer Y, Van Ham SM, Zevenbergen A, Westers TM, Berkhof J, Meijer CJ, van de Loosdrecht AA, Ossenkoppele GJ (2004) Class II-associated invariant chain peptide expression on myeloid leukemic blasts predicts poor clinical outcome. Cancer Res 64:5546– 5550

    PubMed  CAS  Google Scholar 

  • Charbonnier A, Gaugler B, Sainty D, Lafage-Pochitaloff M, Olive D (1999) Human acute myeloblastic leukemia cells differentiate in vitro into mature dendritic cells and induce the differentiation of cytotoxic T cells against autologous leukemias. Eur J Immunol 29:2567–2578

    PubMed  CAS  Google Scholar 

  • Chaturvedi P, Hengeveld R, Zechel MA, Lee-Chan E, Singh B (2000) The functional role of class II-associated invariant chain peptide (CLIP) in its ability to variably modulate immune responses. Int Immunol 12:757–765

    PubMed  CAS  Google Scholar 

  • Chen X, Laur O, Kambayashi T, Li S, Bray RA, Weber DA, Karlsson L, Jensen PE (2002) Regulated expression of human histocompatibility leukocyte antigen (HLA)-DO during antigen-dependent and antigen-independent phases of B cell development. J Exp Med 195:1053–1062

    PubMed  CAS  Google Scholar 

  • Choudhury A, Gajewski JL, Liang JC, Popat U, Claxton DF, Kliche KO, Andreeff M, Champlin RE (1997) Use of leukemic dendritic cells for the generation of antileukemic cellular cytotoxic-ity against Philadelphia chromosome-positive chronic myelogenous leukemia. Blood 89:1133– 1142

    PubMed  CAS  Google Scholar 

  • Choudhury BA, Liang JC, Thomas EK, Flores-Romo L, Xie QS, Agusala K, Sutaria S, Sinha I, Champlin RE, Claxton DF (1999) Dendritic cells derived in vitro from acute myelogenous leukemia cells stimulate autologous, antileukemic T-cell responses. Blood 93:780–786

    PubMed  CAS  Google Scholar 

  • Cignetti A, Bryant E, Allione B, Vitale A, Foa R, Cheever MA (1999) CD34(+) acute myeloid and lymphoid leukemic blasts can be induced to differentiate into dendritic cells. Blood 94:2048– 2055

    PubMed  CAS  Google Scholar 

  • Cignetti A, Vallario A, Roato I, Circosta P, Allione B, Casorzo L, Ghia P, Caligaris-Cappio F (2004) Leukemia-derived immature dendritic cells differentiate into functionally competent mature dendritic cells that efficiently stimulate T cell responses. J Immunol 173:2855–2865

    PubMed  CAS  Google Scholar 

  • Coulie PG, Karanikas V, Colau D, Lurquin C, Landry C, Marchand M, Dorval T, Brichard V, Boon T (2001) A monoclonal cytolytic T-lymphocyte response observed in a melanoma patient vaccinated with a tumor-specific antigenic peptide encoded by gene MAGE-3. Proc Natl Acad Sci USA 98:10290–10295

    PubMed  CAS  Google Scholar 

  • Curiel TJ, Wei S, Dong H, Alvarez X, Cheng P, Mottram P, Krzysiek R, Knutson KL, Daniel B, Zimmermann MC, David O, Burow M, Gordon A, Dhurandhar N, Myers L, Berggren R, Hemminki A, Alvarez RD, Emilie D, Curiel DT, Chen L, Zou W (2003) Blockade of B7-H1 improves myeloid dendritic cell-mediated antitumor immunity. Nat Med 9:562–567

    PubMed  CAS  Google Scholar 

  • Czerniecki BJ, Carter C, Rivoltini L, Koski GK, Kim HI, Weng DE, Roros JG, Hijazi YM, Xu S, Rosenberg SA, Cohen PA (1997) Calcium ionophore-treated peripheral blood monocytes and dendritic cells rapidly display characteristics of activated dendritic cells. J Immunol 159:3823– 3837

    PubMed  CAS  Google Scholar 

  • De Bont ES, Fidler V, Meeuwsen T, Scherpen F, Hahlen K, Kamps WA (2002) Vascular endothelial growth factor secretion is an independent prognostic factor for relapse-free survival in pediatric acute myeloid leukemia patients. Clin Cancer Res 8:2856–2861

    PubMed  Google Scholar 

  • De Vries I, 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 9:5091–5100

    PubMed  Google Scholar 

  • Decker WK, Xing D, Li S, Robinson SN, Yang H, Yao X, Segall H, McMannis JD, Komanduri KV, Champlin RE, Shpall EJ (2006) Double loading of dendritic cell MHC class I and MHC class II with an AML antigen repertoire enhances correlates of T-cell immunity in vitro via amplification of T-cell help. Vaccine 24:3203–3216

    PubMed  CAS  Google Scholar 

  • Delluc S, Tourneur L, Michallet AS, Boix C, Varet B, Fradelizi D, Guillet JG, Buzyn A (2005) Autologous peptides eluted from acute myeloid leukemia cells can be used to generate specific antileukemic CD4 helper and CD8 cytotoxic T lymphocyte responses in vitro. Haematologica 90:1050–1062

    PubMed  CAS  Google Scholar 

  • Delluc S, Tourneur L, Fradelizi D, Rubio MT, Marchiol-Fournigault C, Chiocchia G, Buzyn A (2006) DC-based vaccine loaded with acid-eluted peptides in acute myeloid leukemia: the importance of choosing the best elution method. Cancer Immunol Immunother 56:1–12

    PubMed  Google Scholar 

  • Denzin LK, Sant'Angelo DB, Hammond C, Surman MJ, Cresswell P (1997) Negative regulation by HLA-DO of MHC class II-restricted antigen processing. Science 278:106–109

    PubMed  CAS  Google Scholar 

  • Dhodapkar MV, Steinman RM, Krasovsky J, Munz C, Bhardwaj N (2001) Antigen-specific inhibition of effector T cell function in humans after injection of immature dendritic cells. J Exp Med 193:233–238

    PubMed  CAS  Google Scholar 

  • Dissanayake SK, Tuera N, Ostrand-Rosenberg S (2005) Presentation of endogenously synthesized MHC class II-restricted epitopes by MHC class II cancer vaccines is independent of transporter associated with Ag processing and the proteasome. J Immunol 174:1811–1819

    PubMed  CAS  Google Scholar 

  • Dranoff G, Jaffee E, Lazenby A, Golumbek P, Levitsky H, Brose K, Jackson V, Hamada H, Pardoll D, Mulligan RC (1993) Vaccination with irradiated tumor cells engineered to secrete murine granulocyte-macrophage colony-stimulating factor stimulates potent, specific, and long-lasting anti-tumor immunity. Proc Natl Acad Sci USA 90:3539–3543

    PubMed  CAS  Google Scholar 

  • Dunn GP, Old LJ, Schreiber RD (2004) The immunobiology of cancer immunosurveillance and immunoediting. Immunity 21:137–148

    PubMed  CAS  Google Scholar 

  • Dustin ML, Bivona TG, Philips MR (2004) Membranes as messengers in T cell adhesion signaling. Nat Immunol 5:363–372

    PubMed  CAS  Google Scholar 

  • Egen JG, Allison JP (2002) Cytotoxic T lymphocyte antigen-4 accumulation in the immunological synapse is regulated by TCR signal strength. Immunity 16:23–35

    PubMed  CAS  Google Scholar 

  • Engels FH, Koski GK, Bedrosian I, Xu S, Luger S, Nowell PC, Cohen PA, Czerniecki BJ (1999) Calcium signaling induces acquisition of dendritic cell characteristics in chronic myelogenous leukemia myeloid progenitor cells. Proc Natl Acad Sci USA 96:10332–10337

    PubMed  CAS  Google Scholar 

  • Fabre JW (2001) The allogeneic response and tumor immunity. Nat Med 7:649–652

    PubMed  CAS  Google Scholar 

  • Feller N, van der Pol MA, van SA, Weijers GW, Westra AH, Evertse BW, Ossenkoppele GJ, Schuurhuis GJ (2004) MRD parameters using immunophenotypic detection methods are highly reliable in predicting survival in acute myeloid leukaemia. Leukemia 18:1380–1390

    PubMed  CAS  Google Scholar 

  • Figdor CG, de V, I, Lesterhuis WJ, Melief CJ (2004) Dendritic cell immunotherapy: mapping the way. Nat Med 10:475–480

    PubMed  CAS  Google Scholar 

  • Fong L, Brockstedt D, Benike C, Wu L, Engleman EG (2001) Dendritic cells injected via different routes induce immunity in cancer patients. J Immunol 166:4254–4259

    PubMed  CAS  Google Scholar 

  • Franki SN, Steward KK, Betting DJ, Kafi K, Yamada RE, Timmerman JM (2007) Dendritic cells loaded with apoptotic antibody-coated tumor cells provide protective immunity against B cell lymphoma in vivo. Blood 111:1504–1511

    PubMed  Google Scholar 

  • Friedl P, Storim J (2004) Diversity in immune-cell interactions: states and functions of the im-munological synapse. Trends Cell Biol 14:557–567

    PubMed  CAS  Google Scholar 

  • Fujii S, Shimizu K, Fujimoto K, Kiyokawa T, Shimomura T, Kinoshita M, Kawano F (1999) Analysis of a chronic myelogenous leukemia patient vaccinated with leukemic dendritic cells following autologous peripheral blood stem cell transplantation. Jpn J Cancer Res 90:1117–1129

    PubMed  CAS  Google Scholar 

  • Furumoto K, Soares L, Engleman EG, Merad M (2004) Induction of potent antitumor immunity by in situ targeting of intratumoral DCs. J Clin Invest 113:774–783

    PubMed  CAS  Google Scholar 

  • Gaiger A, Reese V, Disis ML, Cheever MA (2000) Immunity to WT1 in the animal model and in patients with acute myeloid leukemia. Blood 96:1480–1489

    PubMed  CAS  Google Scholar 

  • Gaiger A, Carter L, Greinix H, Carter D, McNeill PD, Houghton RL, Cornellison CD, Vedvick TS, Skeiky YA, Cheever MA (2001) WT1-specific serum antibodies in patients with leukemia. Clin Cancer Res 7:761s–765s

    PubMed  CAS  Google Scholar 

  • Galea-Lauri J (2002) Immunological weapons against acute myeloid leukaemia. Immunology 107:20–27

    PubMed  CAS  Google Scholar 

  • Galea-Lauri J, Wells JW, Darling D, Harrison P, Farzaneh F (2004) Strategies for antigen choice and priming of dendritic cells influence the polarization and efficacy of antitumor T-cell responses in dendritic cell-based cancer vaccination. Cancer Immunol Immunother 53:963–977

    PubMed  CAS  Google Scholar 

  • Gao L, Bellantuono I, Elsasser A, Marley SB, Gordon MY, Goldman JM, Stauss HJ (2000) Selective elimination of leukemic CD34(+) progenitor cells by cytotoxic T lymphocytes specific for WT1. Blood 95:2198–2203

    PubMed  CAS  Google Scholar 

  • Geijtenbeek TB, Krooshoop DJ, Bleijs DA, van Vliet SJ, van Duijnhoven GC, Grabovsky V, Alon R, Figdor CG, van KY (2000a) DC-SIGN-ICAM-2 interaction mediates dendritic cell trafficking. Nat Immunol 1:353–357

    CAS  Google Scholar 

  • Geijtenbeek TB, Torensma R, van Vliet SJ, van Duijnhoven GC, Adema GJ, van KY, Figdor CG (2000b) Identification of DC-SIGN, a novel dendritic cell-specific ICAM-3 receptor that supports primary immune responses. Cell 100:575–585

    CAS  Google Scholar 

  • Glazier KS, Hake SB, Tobin HM, Chadburn A, Schattner EJ, Denzin LK (2002) Germinal center B cells regulate their capability to present antigen by modulation of HLA-DO. J Exp Med 195:1063–1069

    PubMed  CAS  Google Scholar 

  • Hanks BA, Jiang J, Singh RA, Song W, Barry M, Huls MH, Slawin KM, Spencer DM (2005) Re-engineered CD40 receptor enables potent pharmacological activation of dendritic-cell cancer vaccines in vivo. Nat Med 11:130–137

    PubMed  CAS  Google Scholar 

  • Harrison BD, Adams JA, Briggs M, Brereton ML, Yin JA (2001) Stimulation of autologous prolif-erative and cytotoxic T-cell responses by “leukemic dendritic cells” derived from blast cells in acute myeloid leukemia. Blood 97:2764–2771

    PubMed  CAS  Google Scholar 

  • Hart DN (1997) Dendritic cells: unique leukocyte populations which control the primary immune response. Blood 90:3245–3287

    PubMed  CAS  Google Scholar 

  • Hawiger D, Inaba K, Dorsett Y, Guo M, Mahnke K, Rivera M, Ravetch JV, Steinman RM, Nussenzweig MC (2001) Dendritic cells induce peripheral T cell unresponsiveness under steady state conditions in vivo. J Exp Med 194:769–779

    PubMed  CAS  Google Scholar 

  • Hellstrom KE, Hellstrom I (2003) Therapeutic vaccination with tumor cells that engage CD137. J Mol Med 81:71–86

    PubMed  CAS  Google Scholar 

  • Herr W, Ranieri E, Olson W, Zarour H, Gesualdo L, Storkus WJ (2000) Mature dendritic cells pulsed with freeze-thaw cell lysates define an effective in vitro vaccine designed to elicit EBV-specific CD4(+) and CD8(+) T lymphocyte responses. Blood 96:1857–1864

    PubMed  CAS  Google Scholar 

  • Hirano N, Takahashi T, Takahashi T, Azuma M, Okumura K, Yazaki Y, Yagita H, Hirai H (1997) Protective and therapeutic immunity against leukemia induced by irradiated B7–1 (CD80)-transduced leukemic cells. Hum Gene Ther 8:1375–1384

    PubMed  CAS  Google Scholar 

  • Hirano F, Kaneko K, Tamura H, Dong H, Wang S, Ichikawa M, Rietz C, Flies DB, Lau JS, Zhu G, Tamada K, Chen L (2005) Blockade of B7-H1 and PD-1 by monoclonal antibodies potentiates cancer therapeutic immunity. Cancer Res 65:1089–1096

    PubMed  CAS  Google Scholar 

  • Hirst WJ, Buggins A, Darling D, Gaken J, Farzaneh F, Mufti GJ (1997) Enhanced immune cos-timulatory activity of primary acute myeloid leukaemia blasts after retrovirus-mediated gene transfer of B7.1. Gene Ther 4:691–699

    PubMed  CAS  Google Scholar 

  • 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 54:663–670

    PubMed  Google Scholar 

  • Hou WS, Van Parijs L (2004) A Bcl-2-dependent molecular timer regulates the lifespan and im-munogenicity of dendritic cells. Nat Immunol 5:583–589

    PubMed  CAS  Google Scholar 

  • Houtenbos I, Westers TM, Ossenkoppele GJ, van de Loosdrecht AA (2003a) Identification of CD14 as a predictor for leukemic dendritic cell differentiation in acute myeloid leukemia. Leukemia 17:1683–1684

    CAS  Google Scholar 

  • Houtenbos I, Westers TM, Stam AG, de Gruijl TD, Scheper RJ, Ossenkoppele GJ, van de Loosdrecht AA (2003b) Serum-free generation of antigen presenting cells from acute myeloid leukaemic blasts for active specific immunisation. Cancer Immunol Immunother 52:455–462

    Google Scholar 

  • Houtenbos I, Westers TM, de Gruijl TD, Scheper RJ, Ossenkoppele GJ, van de Loosdrecht AA (2004) TNF-alpha receptor 1 expression on acute myeloid leukemic blasts predicts differentiation into leukemic dendritic cells. Leukemia 18:1149–1153

    PubMed  CAS  Google Scholar 

  • Houtenbos I, Westers TM, Ossenkoppele GJ, van de Loosdrecht AA (2006a) Feasibility of clinical dendritic cell vaccination in acute myeloid leukemia. Immunobiology 211:677–685

    CAS  Google Scholar 

  • Houtenbos I, Westers TM, Ossenkoppele GJ, van de Loosdrecht AA (2006b) Leukaemic dendritic cell vaccination for patients with acute myeloid leukaemia. Br J Haematol 134:445–446

    CAS  Google Scholar 

  • Houtenbos I, Westers TM, Ossenkoppele GJ, van de Loosdrecht AA (2006c) Leukemia-derived dendritic cells: towards clinical vaccination protocols in acute myeloid leukemia. Haematolog-ica 91:348–355

    Google Scholar 

  • Houtenbos I, Westers TM, Ossenkoppele GJ, van de Loosdrecht AA, Hess CJ, Waisfisz Q (2006d) Flt-3 internal tandem duplication hampers differentiation of AML blasts towards leukemic dendritic cells. Leukemia 20:2219

    CAS  Google Scholar 

  • Houtenbos I, Westers TM, Ossenkoppele GJ, van de Loosdrecht AA, Hess CJ, Waisfisz Q (2006e) Flt-3 internal tandem duplication hampers differentiation of AML blasts towards leukemic dendritic cells. Leukemia 20:2219

    CAS  Google Scholar 

  • Houtenbos I, Westers TM, Dijkhuis A, de Gruijl TD, Ossenkoppele GJ, van de Loosdrecht AA (2007) Leukemia-specific T-cell reactivity induced by leukemic dendritic cells is augmented by 4–1BB targeting. Clin Cancer Res 13:307–315

    PubMed  CAS  Google Scholar 

  • Hsu FJ, Benike C, Fagnoni F, Liles TM, Czerwinski D, Taidi B, Engleman EG, Levy R (1996) Vaccination of patients with B-cell lymphoma using autologous antigen-pulsed dendritic cells. Nat Med 2:52–58

    PubMed  CAS  Google Scholar 

  • Hus I, Rolinski J, Tabarkiewicz J, Wojas K, Bojarska-Junak A, Greiner J, Giannopoulos K, Dmoszynska A, Schmitt M (2005) Allogeneic dendritic cells pulsed with tumor lysates or apoptotic bodies as immunotherapy for patients with early-stage B-cell chronic lymphocytic leukemia. Leukemia 19:1621–1627

    PubMed  CAS  Google Scholar 

  • Ito F, Li Q, Shreiner AB, Okuyama R, Jure-Kunkel MN, Teitz-Tennenbaum S, Chang AE (2004) Anti-CD137 monoclonal antibody administration augments the antitumor efficacy of dendritic cell-based vaccines. Cancer Res 64:8411–8419

    PubMed  CAS  Google Scholar 

  • Jacobelli J, Andres PG, Boisvert J, Krummel MF (2004) New views of the immunological synapse: variations in assembly and function. Curr Opin Immunol 16:345–352

    PubMed  CAS  Google Scholar 

  • 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 5:20–30

    PubMed  Google Scholar 

  • Jonuleit H, Schmitt E, Schuler G, Knop J, Enk AH (2000) Induction of interleukin 10-producing, nonproliferating CD4(+) T cells with regulatory properties by repetitive stimulation with allo-geneic immature human dendritic cells. J Exp Med 192:1213–1222

    PubMed  CAS  Google Scholar 

  • Kloetzel PM (2004) Generation of major histocompatibility complex class I antigens: functional interplay between proteasomes and TPPII. Nat Immunol 5:661–669

    PubMed  CAS  Google Scholar 

  • Kolb HJ, Schattenberg A, Goldman JM, Hertenstein B, Jacobsen N, Arcese W, Ljungman P, Ferrant A, Verdonck L, Niederwieser D (1995) Graft-versus-leukemia effect of donor lymphocyte transfusions in marrow grafted patients. European Group for Blood and Marrow Transplantation Working Party Chronic Leukemia. Blood 86:2041–2050

    PubMed  CAS  Google Scholar 

  • Koski GK, Schwartz GN, Weng DE, Gress RE, Engels FH, Tsokos M, Czerniecki BJ, Cohen PA (1999) Calcium ionophore-treated myeloid cells acquire many dendritic cell characteristics independent of prior differentiation state, transformation status, or sensitivity to biologic agents. Blood 94:1359–1371

    PubMed  CAS  Google Scholar 

  • Kropshofer H, Vogt AB, Thery C, Armandola EA, Li BC, Moldenhauer G, Amigorena S, Hammerling GJ (1998) A role for HLA-DO as a co-chaperone of HLA-DM in peptide loading of MHC class II molecules. EMBO J 17:2971–2981

    PubMed  CAS  Google Scholar 

  • Langenkamp A, Messi M, Lanzavecchia A, Sallusto F (2000) Kinetics of dendritic cell activation: impact on priming of TH1, TH2 and nonpolarized T cells. Nat Immunol 1:311–316

    PubMed  CAS  Google Scholar 

  • Lau R, Wang F, Jeffery G, Marty V, Kuniyoshi J, Bade E, Ryback ME, Weber J (2001) Phase I trial of intravenous peptide-pulsed dendritic cells in patients with metastatic melanoma. J Immunother 24:66–78

    PubMed  CAS  Google Scholar 

  • Leach DR, Krummel MF, Allison JP (1996) Enhancement of antitumor immunity by CTLA-4 blockade. Science 271:1734–1736

    PubMed  CAS  Google Scholar 

  • Lee KH, Holdorf AD, Dustin ML, Chan AC, Allen PM, Shaw AS (2002) T cell receptor signaling precedes immunological synapse formation. Science 295:1539–1542

    PubMed  CAS  Google Scholar 

  • Lee KH, Dinner AR, Tu C, Campi G, Raychaudhuri S, Varma R, Sims TN, Burack WR, Wu H, Wang J, Kanagawa O, Markiewicz M, Allen PM, Dustin ML, Chakraborty AK, Shaw AS (2003) The immunological synapse balances T cell receptor signaling and degradation. Science 302:1218–1222

    PubMed  CAS  Google Scholar 

  • Levitsky HI, Montgomery J, Ahmadzadeh M, Staveley-O'Carroll K, Guarnieri F, Longo DL, Kwak LW (1996) Immunization with granulocyte-macrophage colony-stimulating factor-transduced, but not B7–1-transduced, lymphoma cells primes idiotype-specific T cells and generates potent systemic antitumor immunity. J Immunol 156:3858–3865

    PubMed  CAS  Google Scholar 

  • Li L, Giannopoulos K, Reinhardt P, Tabarkiewicz J, Schmitt A, Greiner J, Rolinski J, Hus I, Dmoszynska A, Wiesneth M, Schmitt M (2006) Immunotherapy for patients with acute myeloid leukemia using autologous dendritic cells generated from leukemic blasts. Int J Oncol 28:855–861

    PubMed  CAS  Google Scholar 

  • Litzow MR, Dietz AB, Bulur PA, Butler GW, Gastineau DA, Hoering A, Fink SR, Letendre L, Padley DJ, Paternoster SF, Tefferi A, Vuk-Pavlovic S (2006) Testing the safety of clinical-grade mature autologous myeloid DC in a phase I clinical immunotherapy trial of CML. Cytotherapy 8:290–298

    PubMed  CAS  Google Scholar 

  • Lotteau V, Teyton L, Peleraux A, Nilsson T, Karlsson L, Schmid SL, Quaranta V, Peterson PA (1990) Intracellular transport of class II MHC molecules directed by invariant chain. Nature 348:600–605

    PubMed  CAS  Google Scholar 

  • Lowenberg B, Downing JR, Burnett A (1999) Acute myeloid leukemia. N Engl J Med 341:1051– 1062

    PubMed  CAS  Google Scholar 

  • Mackinnon S, Papadopoulos EB, Carabasi MH, Reich L, Collins NH, Boulad F, Castro-Malaspina H, Childs BH, Gillio AP, Kernan NA (1995) Adoptive immunotherapy evaluating escalating doses of donor leukocytes for relapse of chronic myeloid leukemia after bone marrow transplantation: separation of graft-versus-leukemia responses from graft-versus-host disease. Blood 86:1261–1268

    PubMed  CAS  Google Scholar 

  • Maldonado RA, Irvine DJ, Schreiber R, Glimcher LH (2004) A role for the immunological synapse in lineage commitment of CD4 lymphocytes. Nature 431:527–532

    PubMed  CAS  Google Scholar 

  • Masterson AJ, Sombroek CC, de Gruijl TD, Graus YM, van der Vliet HJ, Lougheed SM, van den Eertwegh AJ, Pinedo HM, Scheper RJ (2002) MUTZ-3, a human cell line model for the cytokine-induced differentiation of dendritic cells from CD34+ precursors. Blood 100: 701–703

    PubMed  CAS  Google Scholar 

  • Menetrier-Caux C, Montmain G, Dieu MC, Bain C, Favrot MC, Caux C, Blay JY (1998) Inhibition of the differentiation of dendritic cells from CD34(+) progenitors by tumor cells: role of interleukin-6 and macrophage colony-stimulating factor. Blood 92:4778–4791

    PubMed  CAS  Google Scholar 

  • Miga AJ, Masters SR, Durell BG, Gonzalez M, Jenkins MK, Maliszewski C, Kikutani H, Wade WF, Noelle RJ (2001) Dendritic cell longevity and T cell persistence is controlled by CD154-CD40 interactions. Eur J Immunol 31:959–965

    PubMed  CAS  Google Scholar 

  • Mohty M, Isnardon D, Blaise D, Mozziconacci MJ, Lafage-Pochitaloff M, Briere F, Gastaut JA, Olive D, Gaugler B (2002) Identification of precursors of leukemic dendritic cells differentiated from patients with acute myeloid leukemia. Leukemia 16:2267–2274

    PubMed  CAS  Google Scholar 

  • Molldrem J, Dermime S, Parker K, Jiang YZ, Mavroudis D, Hensel N, Fukushima P, Barrett AJ (1996) Targeted T-cell therapy for human leukemia: cytotoxic T lymphocytes specific for a peptide derived from proteinase 3 preferentially lyse human myeloid leukemia cells. Blood 88:2450–2457

    PubMed  CAS  Google Scholar 

  • Monks CR, Freiberg BA, Kupfer H, Sciaky N, Kupfer A (1998) Three-dimensional segregation of supramolecular activation clusters in T cells. Nature 395:82–86

    PubMed  CAS  Google Scholar 

  • 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 198:1023–1034

    PubMed  CAS  Google Scholar 

  • Neefjes JJ, Stollorz V, Peters PJ, Geuze HJ, Ploegh HL (1990) The biosynthetic pathway of MHC class II but not class I molecules intersects the endocytic route. Cell 61:171–183

    PubMed  CAS  Google Scholar 

  • Nestle FO, Alijagic S, Gilliet M, Sun Y, Grabbe S, Dummer R, Burg G, Schadendorf D (1998) Vaccination of melanoma patients with peptide- or tumor lysate-pulsed dendritic cells. Nat Med 4:328–332

    PubMed  CAS  Google Scholar 

  • Nestle FO, Farkas A, Conrad C (2005) Dendritic-cell-based therapeutic vaccination against cancer. Curr Opin Immunol 17:163–169

    PubMed  CAS  Google Scholar 

  • Neves AR, Ensina LF, Anselmo LB, Leite KR, Buzaid AC, Camara-Lopes LH, Barbuto JA (2005) Dendritic cells derived from metastatic cancer patients vaccinated with allogeneic dendritic cell-autologous tumor cell hybrids express more CD86 and induce higher levels of interferon-gamma in mixed lymphocyte reactions. Cancer Immunol Immunother 54:61–66

    PubMed  CAS  Google Scholar 

  • Obeid M, Tesniere A, Ghiringhelli F, Fimia GM, Apetoh L, Perfettini JL, Castedo M, Mignot G, Panaretakis T, Casares N, Metivier D, Larochette N, van EP, Ciccosanti F, Piacentini M, Zitvogel L, Kroemer G (2007) Calreticulin exposure dictates the immunogenicity of cancer cell death. Nat Med 13:54–61

    PubMed  CAS  Google Scholar 

  • Oehler L, Berer A, Keil F, Weinlander G, Konig M, Haas OA, Lechner K, Geissler K (2000) Generation of dendritic cells from human chronic myelomonocytic leukemia cells in fetal calf serum-free medium. Leuk Lymphoma 38:577–586

    PubMed  CAS  Google Scholar 

  • Okada N, Iiyama S, Okada Y, Mizuguchi H, Hayakawa T, Nakagawa S, Mayumi T, Fujita T, Yamamoto A (2005) Immunological properties and vaccine efficacy of murine dendritic cells simultaneously expressing melanoma-associated antigen and interleukin-12. Cancer Gene Ther 12:72–83

    PubMed  CAS  Google Scholar 

  • Orleans-Lindsay JK, Barber LD, Prentice HG, Lowdell MW (2001) Acute myeloid leukaemia cells secrete a soluble factor that inhibits T and NK cell proliferation but not cytolytic function— implications for the adoptive immunotherapy of leukaemia. Clin Exp Immunol 126:403–411

    PubMed  CAS  Google Scholar 

  • Orleans-Lindsay JK, Deru A, Craig JI, Prentice HG, Lowdell MW (2003) In vitro co-stimulation with anti-CD28 synergizes with IL-12 in the generation of T cell immune responses to leukaemic cells; a strategy for ex-vivo generation of CTL for immunotherapy. Clin Exp Immunol 133:467–475

    PubMed  CAS  Google Scholar 

  • Ossenkoppele GJ, Stam AG, Westers TM, de Gruijl TD, Janssen JJ, van de Loosdrecht AA, Scheper RJ (2003) Vaccination of chronic myeloid leukemia patients with autologous in vitro cultured leukemic dendritic cells. Leukemia 17:1424–1426

    PubMed  CAS  Google Scholar 

  • Panoskaltsis N, Belanger TJ, Liesveld JL, Abboud CN (2002) Optimal cytokine stimulation for the enhanced generation of leukemic dendritic cells in short-term culture. Leuk Res 26:191–201

    PubMed  CAS  Google Scholar 

  • Panoskaltsis N, Reid CD, Knight SC (2003) Quantification and cytokine production of circulating lymphoid and myeloid cells in acute myelogenous leukaemia. Leukemia 17:716–730

    PubMed  CAS  Google Scholar 

  • Pistillo MP, Tazzari PL, Palmisano GL, Pierri I, Bolognesi A, Ferlito F, Capanni P, Polito L, Ratta M, Pileri S, Piccioli M, Basso G, Rissotto L, Conte R, Gobbi M, Stirpe F, Ferrara GB (2003) CTLA-4 is not restricted to the lymphoid cell lineage and can function as a target molecule for apoptosis induction of leukemic cells. Blood 101:202–209

    PubMed  CAS  Google Scholar 

  • Poo WJ, Conrad L, Janeway CA, Jr. (1988) Receptor-directed focusing of lymphokine release by helper T cells. Nature 332:378–380

    PubMed  CAS  Google Scholar 

  • Powles RL, Crowther D, Bateman CJ, Beard ME, McElwain TJ, Russell J, Lister TA, Whitehouse JM, Wrigley PF, Pike M, Alexander P, Fairley GH (1973) Immunotherapy for acute myeloge-nous leukaemia. Br J Cancer 28:365–376

    PubMed  CAS  Google Scholar 

  • Randolph GJ (2001) Dendritic cell migration to lymph nodes: cytokines, chemokines, and lipid mediators. Semin Immunol 13:267–274

    PubMed  CAS  Google Scholar 

  • Re F, Arpinati M, Testoni N, Ricci P, Terragna C, Preda P, Ruggeri D, Senese B, Chirumbolo G, Martelli V, Urbini B, Baccarani M, Tura S, Rondelli D (2002) Expression of CD86 in acute myelogenous leukemia is a marker of dendritic/monocytic lineage. Exp Hematol 30:126–134

    PubMed  CAS  Google Scholar 

  • Renkvist N, Castelli C, Robbins PF, Parmiani G (2001) A listing of human tumor antigens recognized by T cells. Cancer Immunol Immunother 50:3–15

    PubMed  CAS  Google Scholar 

  • Ridgway D (2003) The first 1000 dendritic cell vaccinees. Cancer Invest 21:873–886

    PubMed  Google Scholar 

  • Robinson SP, English N, Jaju R, Kearney L, Knight SC, Reid CD (1998) The in-vitro generation of dendritic cells from blast cells in acute leukaemia. Br J Haematol 103:763–771

    PubMed  CAS  Google Scholar 

  • Roche PA, Cresswell P (1990) Invariant chain association with HLA-DR molecules inhibits im-munogenic peptide binding. Nature 345:615–618

    PubMed  CAS  Google Scholar 

  • Roddie H, Klammer M, Thomas C, Thomson R, Atkinson A, Sproul A, Waterfall M, Samuel K, Yin J, Johnson P, Turner M (2006) Phase I/II study of vaccination with dendritic-like leukaemia cells for the immunotherapy of acute myeloid leukaemia. Br J Haematol 133:152–157

    PubMed  CAS  Google Scholar 

  • Romagnoli P, Germain RN (1994) The CLIP region of invariant chain plays a critical role in regulating major histocompatibility complex class II folding, transport, and peptide occupancy. J Exp Med 180:1107–1113

    PubMed  CAS  Google Scholar 

  • Romani N, Gruner S, Brang D, Kampgen E, Lenz A, Trockenbacher B, Konwalinka G, Fritsch PO, Steinman RM, Schuler G (1994) Proliferating dendritic cell progenitors in human blood. J Exp Med 180:83–93

    PubMed  CAS  Google Scholar 

  • Rosenberg SA, Yang JC, Schwartzentruber DJ, Hwu P, Marincola FM, Topalian SL, Restifo NP, Dudley ME, Schwarz SL, Spiess PJ, Wunderlich JR, Parkhurst MR, Kawakami Y, Seipp CA, Einhorn JH, White DE (1998) Immunologic and therapeutic evaluation of a synthetic peptide vaccine for the treatment of patients with metastatic melanoma. Nat Med 4:321–327

    PubMed  CAS  Google Scholar 

  • Roskrow MA, Dilloo D, Suzuki N, Zhong W, Rooney CM, Brenner MK (1999) Autoimmune disease induced by dendritic cell immunization against leukemia. Leuk Res 23:549–557

    PubMed  CAS  Google Scholar 

  • Roucard C, Thomas C, Pasquier MA, Trowsdale J, Sotto JJ, Neefjes J, Van Ham SM (2001) In vivo and in vitro modulation of HLA-DM and HLA-DO is induced by B lymphocyte activation. J Immunol 167:6849–6858

    PubMed  CAS  Google Scholar 

  • Sallusto F, Lanzavecchia A (1994) Efficient presentation of soluble antigen by cultured human dendritic cells is maintained by granulocyte/macrophage colony-stimulating factor plus interleukin 4 and downregulated by tumor necrosis factor alpha. J Exp Med 179:1109–1118

    PubMed  CAS  Google Scholar 

  • Santegoets SJ, Masterson AJ, van der Sluis PC, Lougheed SM, Fluitsma DM, van den Eertwegh AJ, Pinedo HM, Scheper RJ, de Gruijl TD (2006a) A CD34(+) human cell line model of myeloid dendritic cell differentiation: evidence for a CD14(+)CD11b(+) Langerhans cell precursor. J Leukoc Biol 80:1337–1344

    CAS  Google Scholar 

  • Santegoets SJ, Schreurs MW, Masterson AJ, Liu YP, Goletz S, Baumeister H, Kueter EW, Lougheed SM, van den Eertwegh AJ, Scheper RJ, Hooijberg E, de Gruijl TD (2006b) In vitro priming of tumor-specific cytotoxic T lymphocytes using allogeneic dendritic cells derived from the human MUTZ-3 cell line. Cancer Immunol Immunother 55:1480–1490

    Google Scholar 

  • Saudemont A, Buffenoir G, Denys A, Desreumaux P, Jouy N, Hetuin D, Bauters F, Fenaux P, Quesnel B (2002) Gene transfer of CD154 and IL12 cDNA induces an anti-leukemic immunity in a murine model of acute leukemia. Leukemia 16:1637–1644

    PubMed  CAS  Google Scholar 

  • Saudemont A, Quesnel B (2004) In a model of tumor dormancy, long-term persistent leukemic cells have increased B7-H1 and B7.1 expression and resist CTL-mediated lysis. Blood 104:2124–2133

    PubMed  CAS  Google Scholar 

  • 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 191:423–434

    PubMed  CAS  Google Scholar 

  • Scheibenbogen C, Letsch A, Thiel E, Schmittel A, Mailaender V, Baerwolf S, Nagorsen D, Keil-holz U (2002) CD8 T-cell responses to Wilms tumor gene product WT1 and proteinase 3 in patients with acute myeloid leukemia. Blood 100:2132–2137

    PubMed  CAS  Google Scholar 

  • Schnare M, Barton GM, Holt AC, Takeda K, Akira S, Medzhitov R (2001) Toll-like receptors control activation of adaptive immune responses. Nat Immunol 2:947–950

    PubMed  CAS  Google Scholar 

  • Schui DK, Singh L, Schneider B, Knau A, Hoelzer D, Weidmann E (2002) Inhibiting effects on the induction of cytotoxic T lymphocytes by dendritic cells pulsed with lysates from acute myeloid leukemia blasts. Leuk Res 26:383–389

    PubMed  Google Scholar 

  • Schuler (2006) Dendritic cell vaccination of Melanoma: looking back and ahead after 200 patients. Dendritic Cells; 9th International Conference: S04.01

    Google Scholar 

  • Seya T, Akazawa T, Tsujita T, Matsumoto M (2006) Role of Toll-like receptors in adjuvant-augmented immune therapies. Evid Based Complement Alternat Med 3:31–38

    PubMed  Google Scholar 

  • Sloan VS, Cameron P, Porter G, Gammon M, Amaya M, Mellins E, Zaller DM (1995) Mediation by HLA-DM of dissociation of peptides from HLA-DR. Nature 375:802–806

    PubMed  CAS  Google Scholar 

  • Smits EL, Ponsaerts P, Van de Velde AL, Van Driessche A, Cools N, Lenjou M, Nijs G, Van Bockstaele DR, Berneman ZN, Van Tendeloo V (2007) Proinflammatory response of human leukemic cells to dsRNA transfection linked to activation of dendritic cells. Leukemia 21:1691– 1699

    PubMed  CAS  Google Scholar 

  • Sotomayor EM, Borrello I, Tubb E, Allison JP, Levitsky HI (1999) In vivo blockade of CTLA-4 enhances the priming of responsive T cells but fails to prevent the induction of tumor antigen-specific tolerance. Proc Natl Acad Sci USA 96:11476–11481

    PubMed  CAS  Google Scholar 

  • Spisek R, Charalambous A, Mazumder A, Vesole DH, Jagannath S, Dhodapkar MV (2007) Borte-zomib enhances dendritic cell (DC) mediated induction of immunity to human myeloma via exposure of cell surface heat shock protein 90 on dying tumor cells: therapeutic implications. Blood 109:4839–4845

    PubMed  CAS  Google Scholar 

  • Stary Bangert C, Altrichter S, Strohal R, Kopp T, Stingle G (2006) Dendritic cells with cytotoxic potential after toll-like receptor 7/8-activation. Dendritic Cells, 9th International Conference: S02.03

    Google Scholar 

  • Steinman RM, Turley S, Mellman I, Inaba K (2000) The induction of tolerance by dendritic cells that have captured apoptotic cells. J Exp Med 191:411–416

    PubMed  CAS  Google Scholar 

  • Stumbles PA, Himbeck R, Frelinger JA, Collins EJ, Lake RA, Robinson BW (2004) Cutting edge: tumor-specific CTL are constitutively cross-armed in draining lymph nodes and transiently disseminate to mediate tumor regression following systemic CD40 activation. J Immunol 173:5923–5928

    PubMed  CAS  Google Scholar 

  • Tamir A, Basagila E, Kagahzian A, Jiao L, Jensen S, Nicholls J, Tate P, Stamp G, Farzaneh F, Harrison P, Stauss H, George AJ, Habib N, Lechler RI, Lombardi G (2007) Induction of tumor-specific T-cell responses by vaccination with tumor lysate-loaded dendritic cells in colorectal cancer patients with carcinoembryonic-antigen positive tumors. Cancer Immunol Immunother 56:2003–2016

    PubMed  Google Scholar 

  • Trefzer U, Weingart G, Chen Y, Herberth G, Adrian K, Winter H, Audring H, Guo Y, Sterry W, Walden P (2000) Hybrid cell vaccination for cancer immune therapy: first clinical trial with metastatic melanoma. Int J Cancer 85:618–626

    PubMed  CAS  Google Scholar 

  • TrefzerU,Herberth G, WohlanK,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 110:730–740

    PubMed  CAS  Google Scholar 

  • TrefzerU,Herberth G, WohlanK,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 23:2367–2373

    PubMed  CAS  Google Scholar 

  • Ullrich HJ, Doring K, Gruneberg U, Jahnig F, Trowsdale J, Van Ham SM (1997) Interaction between HLA-DM and HLA-DR involves regions that undergo conformational changes at lyso-somal pH. Proc Natl Acad Sci USA 94:13163–13168

    PubMed  CAS  Google Scholar 

  • Vakkila J, Lotze MT (2004) Inflammation and necrosis promote tumour growth. Nat Rev Immunol 4:641–648

    PubMed  CAS  Google Scholar 

  • Valmori D, Dutoit V, Schnuriger V, Quiquerez AL, Pittet MJ, Guillaume P, Rubio-Godoy V, Walker PR, Rimoldi D, Lienard D, Cerottini JC, Romero P, Dietrich PY (2002) Vaccination with a Melan-A peptide selects an oligoclonal T cell population with increased functional avidity and tumor reactivity. J Immunol 168:4231–4240

    PubMed  CAS  Google Scholar 

  • Van de Loosdrecht AA (2007) The dendritic cell: the piano player in orchestrating the immune response in leukemia. Leuk Lymphoma 48:217–218

    PubMed  Google Scholar 

  • Van de Loosdrecht AA, Beelen RH (2006) Emerging immunobiological concepts in macrophage and dendritic cell research and clinical implications. Immunobiology 211:403–406

    PubMed  Google Scholar 

  • Van Ham SM, Tjin EP, Lillemeier BF, Gruneberg U, van Meijgaarden KE, Pastoors L, Verwoerd D, Tulp A, Canas B, Rahman D, Ottenhoff TH, Pappin DJ, Trowsdale J, Neefjes J (1997) HLA-DO is a negative modulator of HLA-DM-mediated MHC class II peptide loading. Curr Biol 7:950–957

    PubMed  CAS  Google Scholar 

  • Van Ham SM, van Lith M, Lillemeier B, Tjin E, Gruneberg U, Rahman D, Pastoors L, van MK, Roucard C, Trowsdale J, Ottenhoff T, Pappin D, Neefjes J (2000) Modulation of the major histocompatibility complex class II-associated peptide repertoire by human histocompatibility leukocyte antigen (HLA)-DO. J Exp Med 191:1127–1136

    PubMed  Google Scholar 

  • Van Lith M, Van Ham SM, Griekspoor A, Tjin E, Verwoerd D, Calafat J, Janssen H, Reits E, Pastoors L, Neefjes J (2001) Regulation of MHC class II antigen presentation by sorting of recycling HLA-DM/DO and class II within the multivesicular body. J Immunol 167:884–892

    PubMed  Google Scholar 

  • Van Mierlo GJ, den Boer AT, Medema JP, van d, V, Fransen MF, Offringa R, Melief CJ, Toes RE (2002) CD40 stimulation leads to effective therapy of CD40(−) tumors through induction of strong systemic cytotoxic T lymphocyte immunity. Proc Natl Acad Sci USA 99:5561–5566

    PubMed  Google Scholar 

  • Vereecque R, Buffenoir G, Preudhomme C, Hetuin D, Bauters F, Fenaux P, Quesnel B (2000) Gene transfer of GM-CSF, CD80 and CD154 cDNA enhances survival in a murine model of acute leukemia with persistence of a minimal residual disease. Gene Ther 7:1312–1316

    PubMed  CAS  Google Scholar 

  • Waclavicek M, Berer A, Oehler L, Stockl J, Schloegl E, Majdic O, Knapp W (2001) Calcium ionophore: a single reagent for the differentiation of primary human acute myelogenous leukaemia cells towards dendritic cells. Br J Haematol 114:466–473

    PubMed  CAS  Google Scholar 

  • Watts C (2004) The exogenous pathway for antigen presentation on major histocompatibility complex class II and CD1 molecules. Nat Immunol 5:685–692

    PubMed  CAS  Google Scholar 

  • Weigel BJ, Panoskaltsis-Mortari A, Diers M, Garcia M, Lees C, Krieg AM, Chen W, Blazar BR (2006) Dendritic cells pulsed or fused with AML cellular antigen provide comparable in vivo antitumor protective responses. Exp Hematol 34:1403–1412

    PubMed  CAS  Google Scholar 

  • Westers TM, Stam AM, Scheper RM, Regelink JM, Nieuwint AM, Schuurhuis GJ, Van De Loosdrecht AM, Ossenkoppele GM (2003) Rapid generation of antigen-presenting cells from leukaemic blasts in acute myeloid leukaemia. Cancer Immunol Immunother 52:17–27

    PubMed  CAS  Google Scholar 

  • Westers TM, Houtenbos I, Schuurhuis GJ, Ossenkoppele GJ, van de Loosdrecht AA (2005a) Quantification of T-cell-mediated apoptosis in heterogeneous leukemia populations using four-color multiparameter flow cytometry. Cytometry A 66:71–77

    Google Scholar 

  • Westers TM, Houtenbos I, Snoijs NC, van de Loosdrecht AA, Ossenkoppele GJ (2005b) Leukemia-derived dendritic cells in acute myeloid leukemia exhibit potent migratory capacity. Leukemia 19:1270–1272

    CAS  Google Scholar 

  • Westers TM, Houtenbos I, van de Loosdrecht AA, Ossenkoppele GJ (2006) Principles of dendritic cell-based immunotherapy in myeloid leukemia. Immunobiology 211:663–676

    PubMed  CAS  Google Scholar 

  • Westers TM, Ossenkoppele GJ, van de Loosdrecht AA (2007) Dendritic cell-based immunotherapy in acute and chronic myeloid leukaemia. Biomed Pharmacother 61:306–314

    PubMed  CAS  Google Scholar 

  • Wilcox RA, Tamada K, Flies DB, Zhu G, Chapoval AI, Blazar BR, Kast WM, Chen L (2004) Ligation of CD137 receptor prevents and reverses established anergy of CD8+ cytolytic T lymphocytes in vivo. Blood 103:177–184

    PubMed  CAS  Google Scholar 

  • Wilson NS, Behrens GM, Lundie RJ, Smith CM, Waithman J, Young L, Forehan SP, Mount A, Steptoe RJ, Shortman KD, de Koning-Ward TF, Belz GT, Carbone FR, Crabb BS, Heath WR, Villadangos JA (2006) Systemic activation of dendritic cells by Toll-like receptor ligands or malaria infection impairs cross-presentation and antiviral immunity. Nat Immunol 7:165–172

    PubMed  CAS  Google Scholar 

  • Woiciechowsky A, Regn S, Kolb HJ, Roskrow M (2001) Leukemic dendritic cells generated in the presence of FLT3 ligand have the capacity to stimulate an autologous leukemia-specific cytotoxic T cell response from patients with acute myeloid leukemia. Leukemia 15:246–255

    PubMed  CAS  Google Scholar 

  • Zajac AJ, Murali-Krishna K, Blattman JN, Ahmed R (1998) Therapeutic vaccination against chronic viral infection: the importance of cooperation between CD4+ and CD8+ T cells. Curr Opin Immunol 10:444–449

    PubMed  CAS  Google Scholar 

  • Zheng R, Friedman AD, Small D (2002) Targeted inhibition of FLT3 overcomes the block to myeloid differentiation in 32Dcl3 cells caused by expression of FLT3/ITD mutations. Blood 100:4154–4161

    PubMed  CAS  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Department of Haematology, VU-Institute of Cancer and Immunology, VU University Medical Center, Amsterdam, De Boelelaan 1117, 1081 HV, The Netherlands

    A. A. van de Loosdrecht, W. van den Ancker, I. Houtenbos, G. J. Ossenkoppele & T. M. Westers

Authors
  1. A. A. van de Loosdrecht
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. W. van den Ancker
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. I. Houtenbos
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. G. J. Ossenkoppele
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. T. M. Westers
    View author publications

    You can also search for this author in PubMed Google Scholar

Editor information

Editors and Affiliations

  1. DIIID, King's College, London School of Medicine, Guy's Hospital, London, UK

    Giovanna Lombardi (Professor of Human Transplant Immunology MRC Centre in Transplantation Dep. of Nephrology and Transplantation) (Professor of Human Transplant Immunology MRC Centre in Transplantation Dep. of Nephrology and Transplantation)

  2. 5th Floor Hodgkin Building, School of Biomedical and Health Sciences, King's College London, London, SE1 1UL, United Kingdom

    Yanira Riffo-Vasquez (Research Fellow The Sackler Institute of Pulmonary Pharmacology Pharmaceutical Science Division) (Research Fellow The Sackler Institute of Pulmonary Pharmacology Pharmaceutical Science Division)

Rights and permissions

Reprints and permissions

Copyright information

© 2009 Springer-Verlag Berlin Heidelberg

About this chapter

Cite this chapter

van de Loosdrecht, A.A., van den Ancker, W., Houtenbos, I., Ossenkoppele, G.J., Westers, T.M. (2009). Dendritic Cell-Based Immunotherapy in Myeloid Leukaemia: Translating Fundamental Mechanisms into Clinical Applications. In: Lombardi, G., Riffo-Vasquez, Y. (eds) Dendritic Cells. Handbook of Experimental Pharmacology, vol 188. Springer, Berlin, Heidelberg. https://doi.org/10.1007/978-3-540-71029-5_15

Download citation

Publish with us

Policies and ethics

Search

Navigation