Cancer Immunology, Immunotherapy

, Volume 54, Issue 10, pp 933–943

Targeted immunotherapy in acute myeloblastic leukemia: from animals to humans

  • Marie Robin
  • Marie-Hélène Schlageter
  • Christine Chomienne
  • Rose-Ann Padua


Immunity against acute myeloid leukemia (AML) is demonstrated in humans by the graft-versus-leukemia effect in allogeneic hematopoietic stem cell transplantation. Specific leukemic antigens have progressively been discovered and circulating specific T lymphocytes against Wilms tumor antigen, proteinase peptide or fusion-proteins produced from aberrant oncogenic chromosomal translocations have been detected in leukemic patients. However, due to the fact that leukemic blasts develop various escape mechanisms, antileukemic specific immunity is not able to control leukemic cell proliferation. The aim of immunotherapy is to overcome tolerance and boost immunity to elicit an efficient immune response against leukemia. We review different immunotherapy strategies tested in preclinical animal models of AML and the human trials that spurred from encouraging results obtained in animal models, demonstrate the feasibility of immunotherapy in AML patients.


Acute myeloid leukemia Leukemic specific antigen Immunotherapy Dendritic cell vaccine DNA vaccine 


  1. 1.
    Adida C, Haioun C, Gaulard P et al (2000) Prognostic significance of survivin expression in diffuse large B-cell lymphomas. Blood 96:1921–1925PubMedGoogle Scholar
  2. 2.
    Adler A, Chervenick PA, Whiteside TL et al (1988) Interleukin 2 induction of lymphokine-activated killer (LAK) activity in the peripheral blood and bone marrow of acute leukemia patients. I. Feasibility of LAK generation in adult patients with active disease and in remission. Blood 71:709–716PubMedGoogle Scholar
  3. 3.
    Albert ML, Sauter B, Bhardwaj N (1998) Dendritic cells acquire antigen from apoptotic cells and induce class I-restricted CTLs. Nature 392:86–89CrossRefPubMedGoogle Scholar
  4. 4.
    Antoku K, Liu Z, Johnson DE (1997) Inhibition of caspase proteases by CrmA enhances the resistance of human leukemic cells to multiple chemotherapeutic agents. Leukemia 11:1665–1672CrossRefPubMedGoogle Scholar
  5. 5.
    Aversa F, Tabilio A, Velardi A et al (1998) Treatment of high-risk acute leukemia with T-cell-depleted stem cells from related donors with one fully mismatched HLA haplotype. N Engl J Med 339:1186–1193CrossRefPubMedGoogle Scholar
  6. 6.
    Bacigalupo A, Lamparelli T, Gualandi F et al (2001) Increased risk of leukemia relapse with high dose cyclosporine after allogeneic marrow transplantation for acute leukemia: 10 year follow-up of a randomized study. Blood 98:3174–3175CrossRefPubMedGoogle Scholar
  7. 7.
    Bacigalupo A, Van Lint MT, Occhini D et al (1991) Increased risk of leukemia relapse with high-dose cyclosporine A after allogeneic marrow transplantation for acute leukemia. Blood 77:1423–1428PubMedGoogle Scholar
  8. 8.
    Bader P, Klingebiel T, Schaudt A et al (1999) Prevention of relapse in pediatric patients with acute leukemias and MDS after allogeneic SCT by early immunotherapy initiated on the basis of increasing mixed chimerism: a single center experience of 12 children. Leukemia 13:2079–2086CrossRefPubMedGoogle Scholar
  9. 9.
    Boon T, Cerottini JC, Van den Eynde B et al (1994) Tumor antigens recognized by T lymphocytes. Annu Rev Immunol 12:337–365CrossRefPubMedGoogle Scholar
  10. 10.
    Boyer MW, Vallera DA, Taylor PA et al (1997) The role of B7 costimulation by murine acute myeloid leukemia in the generation and function of a CD8+ T-cell line with potent in vivo graft-versus-leukemia properties. Blood 89:3477–3485PubMedGoogle Scholar
  11. 11.
    Bradbury DA, Zhu YM and Russell NH (1997) Bcl-2 expression in acute myeloblastic leukaemia: relationship with autonomous growth and CD34 antigen expression. Leuk Lymphoma 24:221–228PubMedGoogle Scholar
  12. 12.
    Brossart P, Schneider A, Dill P et al (2001) The epithelial tumor antigen MUC1 is expressed in hematological malignancies and is recognized by MUC1-specific cytotoxic T-lymphocytes. Cancer Res 61:6846–6850PubMedGoogle Scholar
  13. 13.
    Bruserud O (1992) Effect of dipyridamole, theophyllamine and verapamil on spontaneous in vitro proliferation of myelogenous leukaemia cells. Acta Oncol 31:53–58PubMedGoogle Scholar
  14. 14.
    Bruserud O and Ulvestad E (1999) Effects of gamma-irradiation on acute myelogenous leukemia blasts: in vitro studies of proliferation, constitutive cytokine secretion, and accessory cell function during T cell activation. J Hematother Stem Cell Res 8:431–441CrossRefPubMedGoogle Scholar
  15. 15.
    Bruserud O and Ulvestad E (2000) Acute myelogenous leukemia blasts as accessory cells during in vitro T lymphocyte activation. Cell Immunol 206:36–50CrossRefPubMedGoogle Scholar
  16. 16.
    Bruserud O and Ulvestad E (2000) Soluble Fas/Apo-1 (CD95) levels during T cell activation in the presence of acute myelogenous leukemia accessory cells; contributions from local release and variations in systemic levels. Cancer Immunol Immunother 49:377–387CrossRefPubMedGoogle Scholar
  17. 17.
    Cassinat B, Chevret S, Zassadowski F et al (2001) In vitro all-trans retinoic acid sensitivity of acute promyelocytic leukemia blasts: a novel indicator of poor patient outcome. Blood 98:2862–2864CrossRefPubMedGoogle Scholar
  18. 18.
    Cassinat B, Zassadowski F, Balitrand N et al (2000) Quantitation of minimal residual disease in acute promyelocytic leukemia patients with t(15;17) translocation using real-time RT-PCR. Leukemia 14:324–328CrossRefPubMedGoogle Scholar
  19. 19.
    Caux C, Dezutter-Dambuyant C, Schmitt D et al (1992) GM-CSF and TNF-alpha cooperate in the generation of dendritic Langerhans cells. Nature 360:258–261CrossRefPubMedGoogle Scholar
  20. 20.
    Charbonnier A, Gaugler B, Sainty D et al (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 29:2567–2578CrossRefPubMedGoogle Scholar
  21. 21.
    Choi SJ, Lee JH, Kim S et al (2004) Treatment of relapsed acute myeloid leukemia after allogeneic bone marrow transplantation with chemotherapy followed by G-CSF-primed donor leukocyte infusion: a high incidence of isolated extramedullary relapse. Leukemia 18:1789–1797CrossRefPubMedGoogle Scholar
  22. 22.
    Chomienne C, Ballerini P, Balitrand N et al (1990) The retinoic acid receptor alpha gene is rearranged in retinoic acid- sensitive promyelocytic leukemias. Leukemia 4:802–807PubMedGoogle Scholar
  23. 23.
    Choudhury BA, Liang JC, Thomas EK et al (1999) Dendritic cells derived in vitro from acute myelogenous leukemia cells stimulate autologous, antileukemic T-cell responses. Blood 93:780–786PubMedGoogle Scholar
  24. 24.
    Cignetti A, Bryant E, Allione B et al (1999) CD34(+) acute myeloid and lymphoid leukemic blasts can be induced to differentiate into dendritic cells. Blood 94:2048–2055PubMedGoogle Scholar
  25. 25.
    Coley W (1893) The treatment of malignant tumors by repeated inoculations of erysipelas: With a report of ten original cases. Am J Med Sci 105:487–511Google Scholar
  26. 26.
    Collins RH Jr, Shpilberg O, Drobyski WR et al (1997) Donor leukocyte infusions in 140 patients with relapsed malignancy after allogeneic bone marrow transplantation. J Clin Oncol 15:433–444PubMedGoogle Scholar
  27. 27.
    Csako G, Binder RA, Kales AN et al (1980) Cloning of human lymphocytes reactive with autologous leukemia cells. Cancer Res 40:3218–3221PubMedGoogle Scholar
  28. 28.
    Da Silva N, Meyer-Monard S, Menot ML et al (2000) Functional G-CSF pathways in t(8;21) leukemic cells allow for differentiation induction and degradation of AML1-ETO. Hematol J 1:316–328CrossRefPubMedGoogle Scholar
  29. 29.
    D’Amico G, Vulcano M, Bugarin C et al (2004) CD40 activation of BCP-ALL cells generates IL-10-producing, IL-12-defective APCs that induce allogeneic T-cell anergy. Blood 104:744–751CrossRefPubMedGoogle Scholar
  30. 30.
    del Canizo C, Galende J, Almeida J et al (1999) In vitro growth in acute myeloblastic leukemia: clinico-biological correlations. Leuk Lymphoma 36:1–7PubMedGoogle Scholar
  31. 31.
    Delves PJ, Roitt IM (2000) The immune system. First of two parts. N Engl J Med 343:37–49CrossRefPubMedGoogle Scholar
  32. 32.
    Dengler R, Munstermann U, al-Batran S et al (1995) Immunocytochemical and flow cytometric detection of proteinase 3 (myeloblastin) in normal and leukaemic myeloid cells. Br J Haematol 89:250–257PubMedGoogle Scholar
  33. 33.
    Dunussi-Joannopoulos K, Dranoff G, Weinstein HJ et al (1998) Gene immunotherapy in murine acute myeloid leukemia: granulocyte-macrophage colony-stimulating factor tumor cell vaccines elicit more potent antitumor immunity compared with B7 family and other cytokine vaccines. Blood 91:222–230PubMedGoogle Scholar
  34. 34.
    Dunussi-Joannopoulos K, Runyon K, Erickson J et al (1999) Vaccines with interleukin-12-transduced acute myeloid leukemia cells elicit very potent therapeutic and long-lasting protective immunity. Blood 94:4263–4273PubMedGoogle Scholar
  35. 35.
    Dunussi-Joannopoulos K, Weinstein HJ, Arceci RJ et al (1997) Gene therapy with B7.1 and GM-CSF vaccines in a murine AML model. J Pediatr Hematol Oncol 19:536–540CrossRefPubMedGoogle Scholar
  36. 36.
    Dunussi-Joannopoulos K, Weinstein HJ, Nickerson PW et al (1996) Irradiated B7–1 transduced primary acute myelogenous leukemia (AML) cells can be used as therapeutic vaccines in murine AML. Blood 87:2938–2946PubMedGoogle Scholar
  37. 37.
    Elisseeva OA, Oka Y, Tsuboi A et al (2002) Humoral immune responses against Wilms tumor gene WT1 product in patients with hematopoietic malignancies. Blood 99:3272–3279CrossRefPubMedGoogle Scholar
  38. 38.
    Falkenburg JH, Faber LM, van den Elshout M et al (1993) Generation of donor-derived antileukemic cytotoxic T-lymphocyte responses for treatment of relapsed leukemia after allogeneic HLA-identical bone marrow transplantation. J Immunother 14:305–309PubMedGoogle Scholar
  39. 39.
    Falkenburg JH, Smit WM and Willemze R (1997) Cytotoxic T-lymphocyte (CTL) responses against acute or chronic myeloid leukemia. Immunol Rev 157:223–230PubMedGoogle Scholar
  40. 40.
    Fenaux P, Chevret S, Guerci A et al (2000) Long-term follow-up confirms the benefit of all-trans retinoic acid in acute promyelocytic leukemia. European APL group. Leukemia 14:1371–1377CrossRefPubMedGoogle Scholar
  41. 41.
    Fernandez NC, Lozier A, Flament C et al (1999) Dendritic cells directly trigger NK cell functions: cross-talk relevant in innate anti-tumor immune responses in vivo. Nat Med 5:405–411CrossRefPubMedGoogle Scholar
  42. 42.
    Frydecka I, Kosmaczewska A, Bocko D et al (2004) Alterations of the expression of T-cell-related costimulatory CD28 and downregulatory CD152 (CTLA-4) molecules in patients with B-cell chronic lymphocytic leukaemia. Br J Cancer 90:2042–2048CrossRefPubMedGoogle Scholar
  43. 43.
    Fujii S, Fujimoto K, Shimizu K et al (1999) Presentation of tumor antigens by phagocytic dendritic cell clusters generated from human CD34+ hematopoietic progenitor cells: induction of autologous cytotoxic T lymphocytes against leukemic cells in acute myelogenous leukemia patients. Cancer Res 59:2150–2158PubMedGoogle Scholar
  44. 44.
    Gaiger A, Reese V, Disis ML et al (2000) Immunity to WT1 in the animal model and in patients with acute myeloid leukemia. Blood 96:1480–1489PubMedGoogle Scholar
  45. 45.
    Gaiger A, Schmid D, Heinze G et al (1998) Detection of the WT1 transcript by RT-PCR in complete remission has no prognostic relevance in de novo acute myeloid leukemia. Leukemia 12:1886–1894CrossRefPubMedGoogle Scholar
  46. 46.
    Galea-Lauri J, Darling D, Mufti G et al (2002) Eliciting cytotoxic T lymphocytes against acute myeloid leukemia-derived antigens: evaluation of dendritic cell-leukemia cell hybrids and other antigen-loading strategies for dendritic cell-based vaccination. Cancer Immunol Immunother 51:299–310CrossRefPubMedGoogle Scholar
  47. 47.
    Gallucci S, Lolkema M and Matzinger P (1999) Natural adjuvants: endogenous activators of dendritic cells. Nat Med 5:1249–1255CrossRefPubMedGoogle Scholar
  48. 48.
    Gambacorti-Passerini C, Grignani F, Arienti F et al (1993) Human CD4 lymphocytes specifically recognize a peptide representing the fusion region of the hybrid protein pml/RAR alpha present in acute promyelocytic leukemia cells. Blood 81:1369–1375PubMedGoogle Scholar
  49. 49.
    Gluckman JC, Canque B, Chapuis F et al (1997) In vitro generation of human dendritic cells and cell therapy. Cytokines Cell Mol Ther 3:187–196PubMedGoogle Scholar
  50. 50.
    Graf M, Hecht K, Reif S et al (2004) Expression and prognostic value of hemopoietic cytokine receptors in acute myeloid leukemia (AML): implications for future therapeutical strategies. Eur J Haematol 72:89–106CrossRefPubMedGoogle Scholar
  51. 51.
    Granatek CH, Ezaki K, Hersh EM et al (1981) Antibody responses of remission leukemia patients receiving active specific and nonspecific immunotherapy. Cancer 47:272–279PubMedGoogle Scholar
  52. 52.
    Guerra N, Guillard M, Angevin E et al (2000) Killer inhibitory receptor (CD158b) modulates the lytic activity of tumor-specific T lymphocytes infiltrating renal cell carcinomas. Blood 95:2883–2889PubMedGoogle Scholar
  53. 53.
    Harrison BD, Adams JA, Briggs M et al (2001) Stimulation of autologous proliferative and cytotoxic T-cell responses by “leukemic dendritic cells” derived from blast cells in acute myeloid leukemia. Blood 97:2764–2771CrossRefPubMedGoogle Scholar
  54. 54.
    Hermans IF, Ritchie DS, Yang J et al (2000) CD8+ T cell-dependent elimination of dendritic cells in vivo limits the induction of antitumor immunity. J Immunol 164:3095–3101PubMedGoogle Scholar
  55. 55.
    Heslop HE, Stevenson FK, Molldrem JJ (2003) Immunotherapy of hematologic malignancy. Hematology (Am Soc Hematol Educ Program) 331–349Google Scholar
  56. 56.
    Hirst WJ, Buggins A, Darling D et al (1997) Enhanced immune costimulatory activity of primary acute myeloid leukaemia blasts after retrovirus-mediated gene transfer of B7.1. Gene Ther 4:691–699CrossRefPubMedGoogle Scholar
  57. 57.
    Huygen K, Content J, Denis O et al (1996) Immunogenicity and protective efficacy of a tuberculosis DNA vaccine [see comments]. Nat Med 2:893–898CrossRefPubMedGoogle Scholar
  58. 58.
    Kapelushnik J, Nagler A, Or R et al (1996) Activated allogeneic cell therapy (allo-ACT) for relapsed chronic myelogenous leukemia (CML) refractory to buffy coat transfusions post-allogeneic bone marrow transplantation. Bone Marrow Transplant 18:1153–1156PubMedGoogle Scholar
  59. 59.
    Kohler T, Plettig R, Wetzstein W et al (2000) Cytokine-driven differentiation of blasts from patients with acute myelogenous and lymphoblastic leukemia into dendritic cells. Stem Cells 18:139–147CrossRefPubMedGoogle Scholar
  60. 60.
    Kolb HJ (1998) Donor leukocyte transfusions for treatment of leukemic relapse after bone marrow transplantation. EBMT Immunology and Chronic Leukemia Working Parties. Vox Sang 74:321–329PubMedGoogle Scholar
  61. 61.
    Kolb HJ, Schmid C, Barrett AJ et al (2004) Graft-versus-leukemia reactions in allogeneic chimeras. Blood 103:767–776CrossRefPubMedGoogle Scholar
  62. 62.
    Leach DR, Krummel MF and Allison JP (1996) Enhancement of antitumor immunity by CTLA-4 blockade. Science 271:1734–1736PubMedGoogle Scholar
  63. 63.
    Lee JJ, Kook H, Park MS et al (2004) Immunotherapy using autologous monocyte-derived dendritic cells pulsed with leukemic cell lysates for acute myeloid leukemia relapse after autologous peripheral blood stem cell transplantation. J Clin Apheresis 19:66–70CrossRefPubMedGoogle Scholar
  64. 64.
    Li L, Schmitt A, Reinhardt P et al (2003) Reconstitution of CD40 and CD80 in dendritic cells generated from blasts of patients with acute myeloid leukemia. Cancer Immun 3:8CrossRefPubMedGoogle Scholar
  65. 65.
    Locatelli F, Zecca M, Rondelli R et al (2000) Graft versus host disease prophylaxis with low-dose cyclosporine-A reduces the risk of relapse in children with acute leukemia given HLA-identical sibling bone marrow transplantation: results of a randomized trial. Blood 95:1572–1579PubMedGoogle Scholar
  66. 66.
    Maraninchi D, Blaise D, Viens P et al (1991) High-dose recombinant interleukin-2 and acute myeloid leukemias in relapse. Blood 78:2182–2187PubMedGoogle Scholar
  67. 67.
    Maraninchi D, Vey N, Viens P et al (1998) A phase II study of interleukin-2 in 49 patients with relapsed or refractory acute leukemia. Leuk Lymphoma 31:343–349PubMedGoogle Scholar
  68. 68.
    Marijt WA, Heemskerk MH, Kloosterboer FM et al (2003) Hematopoiesis-restricted minor histocompatibility antigens HA-1- or HA-2-specific T cells can induce complete remissions of relapsed leukemia. Proc Natl Acad Sci USA 100:2742–2747CrossRefPubMedGoogle Scholar
  69. 69.
    Marmont AM, Horowitz MM, Gale RP et al (1991) T-cell depletion of HLA-identical transplants in leukemia. Blood 78:2120–2130PubMedGoogle Scholar
  70. 70.
    Matulonis UA, Dosiou C, Lamont C et al (1995) Role of B7-1 in mediating an immune response to myeloid leukemia cells. Blood 85:2507–2515PubMedGoogle Scholar
  71. 71.
    Maywald O, Buchheidt D, Bergmann J et al (2004) Spontaneous remission in adult acute myeloid leukemia in association with systemic bacterial infection-case report and review of the literature. Ann Hematol 83:189–194CrossRefPubMedGoogle Scholar
  72. 72.
    Mohty M, Isnardon D, Blaise D et al (2002) Identification of precursors of leukemic dendritic cells differentiated from patients with acute myeloid leukemia. Leukemia 16:2267–2274CrossRefPubMedGoogle Scholar
  73. 73.
    Molldrem J, Dermime S, Parker K et al (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 88:2450–2457PubMedGoogle Scholar
  74. 74.
    Molldrem JJ, Lee PP, Wang C et al (2000) Evidence that specific T lymphocytes may participate in the elimination of chronic myelogenous leukemia. Nat Med 6:1018–1023CrossRefPubMedGoogle Scholar
  75. 75.
    Montagna D, Arico M, Montini E et al (1995) Identification of HLA-unrestricted CD8+/CD28- cytotoxic T-cell clones specific for leukemic blasts in children with acute leukemia. Cancer Res 55:3835–3839PubMedGoogle Scholar
  76. 76.
    Montagna D, Locatelli F, Calcaterra V et al (1998) Does the emergence and persistence of donor-derived leukaemia-reactive cytotoxic T lymphocytes protect patients given an allogeneic BMT from recurrence? Results of a preliminary study. Bone Marrow Transplant 22:743–750CrossRefPubMedGoogle Scholar
  77. 77.
    Montagna D, Maccario R, Locatelli F et al (2001) Ex vivo priming for long-term maintenance of antileukemia human cytotoxic T cells suggests a general procedure for adoptive immunotherapy. Blood 98:3359–3366CrossRefPubMedGoogle Scholar
  78. 78.
    Montagna D, Maccario R, Montini E et al (2003) Generation and ex vivo expansion of cytotoxic T lymphocytes directed toward different types of leukemia or myelodysplastic cells using both HLA-matched and partially matched donors. Exp Hematol 31:1031–1038CrossRefPubMedGoogle Scholar
  79. 79.
    Muller CI, Trepel M, Kunzmann R et al (2004) Hematologic and molecular spontaneous remission following sepsis in acute monoblastic leukemia with translocation (9;11): a case report and review of the literature. Eur J Haematol 73:62–66CrossRefPubMedGoogle Scholar
  80. 80.
    Mutis T, Verdijk R, Schrama E et al (1999) Feasibility of immunotherapy of relapsed leukemia with ex vivo- generated cytotoxic T lymphocytes specific for hematopoietic system- restricted minor histocompatibility antigens. Blood 93:2336–2341PubMedGoogle Scholar
  81. 81.
    Nadal E, Fowler A, Kanfer E et al (2004) Adjuvant interleukin-2 therapy for patients refractory to donor lymphocyte infusions. Exp Hematol 32:218–223CrossRefPubMedGoogle Scholar
  82. 82.
    Nakajima H, Kawasaki K, Oka Y et al (2004) WT1 peptide vaccination combined with BCG-CWS is more efficient for tumor eradication than WT1 peptide vaccination alone. Cancer Immunol Immunother 53:617–624CrossRefPubMedGoogle Scholar
  83. 83.
    Nara N, Kurokawa H, Tanikawa S et al (1994) Prognostic significance of the blast self-renewal capacity in patients with acute myeloid leukemia. Cancer 73:92–97PubMedGoogle Scholar
  84. 84.
    Notter M, Willinger T, Erben U et al (2001) Targeting of a B7–1 (CD80) immunoglobulin G fusion protein to acute myeloid leukemia blasts increases their costimulatory activity for autologous remission T cells. Blood 97:3138–3145CrossRefPubMedGoogle Scholar
  85. 85.
    O’Doherty U, Peng M, Gezelter S et al (1994) Human blood contains two subsets of dendritic cells, one immunologically mature and the other immature. Immunology 82:487–493PubMedGoogle Scholar
  86. 86.
    Padua RA, Larghero J, Robin M et al (2003) PML-RARA-targeted DNA vaccine induces protective immunity in a mouse model of leukemia. Nat Med 9:1413–1417CrossRefPubMedGoogle Scholar
  87. 87.
    Padua RA, Chomienne C (2004) Use of animals models for the treatment of leukemias: Efficacy of DNA vaccination combined with ATRA. Discov Med 4:41Google Scholar
  88. 88.
    Pawlowska AB, Hashino S, McKenna H et al (2001) In vitro tumor-pulsed or in vivo Flt3 ligand-generated dendritic cells provide protection against acute myelogenous leukemia in nontransplanted or syngeneic bone marrow-transplanted mice. Blood 97:1474–1482CrossRefPubMedGoogle Scholar
  89. 89.
    Porter DL, Collins RH, Jr., Hardy C et al (2000) Treatment of relapsed leukemia after unrelated donor marrow transplantation with unrelated donor leukocyte infusions. Blood 95:1214–1221PubMedGoogle Scholar
  90. 90.
    Reid DC (2001) Dendritic cells and immunotherapy for malignant disease. Br J Haematol 112:874–887CrossRefPubMedGoogle Scholar
  91. 91.
    Rissoan MC, Soumelis V, Kadowaki N et al (1999) Reciprocal control of T helper cell and dendritic cell differentiation. Science 283:1183–1186CrossRefPubMedGoogle Scholar
  92. 92.
    Roskrow MA, Dilloo D, Suzuki N et al (1999) Autoimmune disease induced by dendritic cell immunization against leukemia. Leuk Res 23:549–557CrossRefPubMedGoogle Scholar
  93. 93.
    Ruggeri L, Capanni M, Urbani E et al (2002) Effectiveness of donor natural killer cell alloreactivity in mismatched hematopoietic transplants. Science 295:2097–2100CrossRefPubMedGoogle Scholar
  94. 94.
    Sauer MG, Ericson ME, Weigel BJ et al (2004) A novel system for simultaneous in vivo tracking and biological assessment of leukemia cells and ex vivo generated leukemia-reactive cytotoxic T cells. Cancer Res 64:3914–3921PubMedGoogle Scholar
  95. 95.
    Schui DK, Singh L, Schneider B et al (2002) Inhibiting effects on the induction of cytotoxic T lymphocytes by dendritic cells pulsed with lysates from acute myeloid leukemia blasts. Leuk Res 26:383–389CrossRefPubMedGoogle Scholar
  96. 96.
    Semba RD, Muhilal, Ward BJ et al (1993) Abnormal T-cell subset proportions in vitamin-A-deficient children. Lancet 341:5–8CrossRefPubMedGoogle Scholar
  97. 97.
    Semba RD, Munasir Z, Beeler J et al (1995) Reduced seroconversion to measles in infants given vitamin A with measles vaccination. Lancet 345:1330–1332CrossRefPubMedGoogle Scholar
  98. 98.
    Shiobara S, Nakao S, Ueda M et al (2000) Donor leukocyte infusion for Japanese patients with relapsed leukemia after allogeneic bone marrow transplantation: lower incidence of acute graft-versus-host disease and improved outcome. Bone Marrow Transplant 26:769–774CrossRefPubMedGoogle Scholar
  99. 99.
    Slavin S, Ackerstein A, Morecki S et al (2001) Immunotherapy of relapsed resistant chronic myelogenous leukemia post allogeneic bone marrow transplantation with alloantigen pulsed donor lymphocytes. Bone Marrow Transplant 28:795–798CrossRefPubMedGoogle Scholar
  100. 100.
    Slavin S, Naparstek E, Nagler A et al (1996) Allogeneic cell therapy with donor peripheral blood cells and recombinant human interleukin-2 to treat leukemia relapse after allogeneic bone marrow transplantation. Blood 87:2195–2204PubMedGoogle Scholar
  101. 101.
    Spisek R, Chevallier P, Morineau N et al (2002) Induction of leukemia-specific cytotoxic response by cross-presentation of late-apoptotic leukemic blasts by autologous dendritic cells of nonleukemic origin. Cancer Res 62:2861–2868PubMedGoogle Scholar
  102. 102.
    Stevenson FK, Zhu D, King CA et al (1995) Idiotypic DNA vaccines against B-cell lymphoma. Immunol Rev 145:211–228PubMedGoogle Scholar
  103. 103.
    Stine KC, Warren BA and Becton DL (1998) Interleukin-12 (IL-12) enhances lysis of non-lymphoid leukemia cell lines in vitro. Leukemia 12:1204–1209CrossRefPubMedGoogle Scholar
  104. 104.
    Tascon RE, Colston MJ, Ragno S et al (1996) Vaccination against tuberculosis by DNA injection. Nat Med 2:888–892CrossRefPubMedGoogle Scholar
  105. 105.
    Teichmann JV, Ludwig WD and Thiel E (1992) Susceptibility of human leukemia to allogeneic and autologous lymphokine-activated killer cell activity: analysis of 252 samples. Nat Immunol 11:117–132Google Scholar
  106. 106.
    Vitale A, Guarini A, Latagliata R et al (1998) Cytotoxic effectors activated by low-dose IL-2 plus IL-12 lyse IL-2-resistant autologous acute myeloid leukaemia blasts. Br J Haematol 101:150–157CrossRefPubMedGoogle Scholar
  107. 107.
    Vourka-Karussis U, Karussis D, Ackerstein A et al (1995) Enhancement of GVL effect with rhIL-2 following BMT in a murine model for acute myeloid leukemia in SJL/J mice. Exp Hematol 23:196–201PubMedGoogle Scholar
  108. 108.
    Waisman A, Ruiz PJ, Hirschberg DL et al (1996) Suppressive vaccination with DNA encoding a variable region gene of the T-cell receptor prevents autoimmune encephalomyelitis and activates Th2 immunity [see comments]. Nat Med 2:899–905CrossRefPubMedGoogle Scholar
  109. 109.
    Walker PR, Saas P and Dietrich PY (1998) Tumor expression of Fas ligand (CD95L) and the consequences. Curr Opin Immunol 10:564–572CrossRefPubMedGoogle Scholar
  110. 110.
    Weiden PL, Flournoy N, Sanders JE et al (1981) Antileukemic effect of graft-versus-host disease contributes to improved survival after allogeneic marrow transplantation. Transplant Proc 13:248–251PubMedGoogle Scholar
  111. 111.
    Weigel BJ, Nath N, Taylor PA et al (2002) Comparative analysis of murine marrow-derived dendritic cells generated by Flt3L or GM-CSF/IL-4 and matured with immune stimulatory agents on the in vivo induction of antileukemia responses. Blood 100:4169–4176CrossRefPubMedGoogle Scholar
  112. 112.
    Westers TM, Stam AG, Scheper RJ et al (2003) Rapid generation of antigen-presenting cells from leukaemic blasts in acute myeloid leukaemia. Cancer Immunol Immunother 52:17–27CrossRefPubMedGoogle Scholar
  113. 113.
    Woiciechowsky A, Regn S, Kolb HJ et al (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 15:246–255CrossRefPubMedGoogle Scholar
  114. 114.
    Zeis M, Siegel S, Wagner A et al (2003) Generation of cytotoxic responses in mice and human individuals against hematological malignancies using survivin-RNA-transfected dendritic cells. J Immunol 170:5391–5397PubMedGoogle Scholar
  115. 115.
    Zhang B, Wang Y, Zheng GG et al (2002) Clinical significance of IL-18 gene over-expression in AML. Leuk Res 26:887–892CrossRefPubMedGoogle Scholar

Copyright information

© Springer-Verlag 2005

Authors and Affiliations

  • Marie Robin
    • 1
    • 2
  • Marie-Hélène Schlageter
    • 1
    • 3
  • Christine Chomienne
    • 1
    • 3
  • Rose-Ann Padua
    • 1
    • 4
  1. 1.LBCH INSERM U718, Hôpital Saint Louis APHPInstitut Universitaire d’HématologieParisFrance
  2. 2.Service de Greffe de MoelleHôpital Saint LouisParisFrance
  3. 3.Service de Médecine NucléaireHôpital Saint-LouisParisFrance
  4. 4.Department of Haematological MedicineKing’s College LondonUnited Kingdom
  5. 5.INSERM U718Institut Universitaire d’Hématologie, Hôpital Saint-LouisParisFrance

Personalised recommendations