Vaccines for Hematological Malignancies

Part of the Cancer Drug Discovery and Development book series (CDD&D)


High-dose chemotherapy supported by autologous stem-cell transplantation has shown considerable promise as an effective and, in some situations, potentially curable approach to hematological malignancies including leukemias, lymphomas, and multiple myeloma (MM), which are otherwise refractory to conventional chemotherapy modalities. This is attested to by the substantial increase in the number of complete remissions experienced by patients over what had been achieved with standard therapy, and by the significant prolongation of event-free and overall survival times (1). However, despite advances in supportive care, continuing refinement of chemotherapy-conditioning regimens, and combinational maintenance therapy, relapse of the underlying diseases remains the primary cause of treatment failure (1). Thus, novel therapeutic approaches that have a mode of action different from and non-cross-resistant with cytotoxic chemotherapy are required to eradicate tumor cells that have become multidrug-resistant. For this reason, strategies for post-transplantation immunomodulation would be desirable. To this end, immunotherapy aimed at inducing or enhancing tumor-specific immunity in tumor-bearing patients may be useful for the control or even eradication of the remaining tumor cells.


Multiple Myeloma Acute Myeloid Leukemia Chronic Myeloid Leukemia Myeloma Cell Myeloma Patient 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.


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  1. 1.
    Negrin RS, Blume KG. Allogeneic and autologous hematopoietic cell transplantation. In: Beutler E, Lichtman MA, Coller BS, Kipps TJ, Seligsohn U, eds. Williams hematology, 5th ed. New York: McGraw-Hill Medical Publishing Division, 2001;209–235.Google Scholar
  2. 2.
    Press OW, Leonard JP, Coiffier B, Levy R, Timmerman J. Immunotherapy of non-Hodgkin’s lym. phoma. Hematology (Am Soc Hematol Educ Program) 2001; 221–240.Google Scholar
  3. 3.
    Countouriotis A, Moore TB, Sakamoto KM. Cell surface antigen and molecular targeting in the treatment of hematologic malignancies. Stem Cells 2002: 20:215–229.PubMedGoogle Scholar
  4. 4.
    Carter P. Improving the efficacy of antibody-based therapies. Nat Rev Cancer 2001; 1:118–129.PubMedGoogle Scholar
  5. 5.
    Nestle FO. Dendritic cell vaccination for cancer therapy. Oncogene 2000; 19:6673–6679.PubMedGoogle Scholar
  6. 6.
    Smyth MJ, Godfrey DI, Trapani JA. A fresh look at tumor immunosurveillance and immunotherapy. Nat Immunol 2001: 2:293–299.PubMedGoogle Scholar
  7. 7.
    Steinman RM, Cohn ZA. Identification of a novel cell type in peripheral lymphoid organs of mice. I. Morphology, quantitation, tissue distribution. J Exp Med 1973; 137:1142–1162.PubMedGoogle Scholar
  8. 8.
    Steinman RM. The dendritic cell system and its role in immunogenicity. Annu Rev Immunol 1991; 9:271–296.PubMedGoogle Scholar
  9. 9.
    Banchereau J, Steinman RM. Dendritic cells and the control of immunity. Nature 1988; 392:245–252.Google Scholar
  10. 10.
    Lynch RG, Graff RJ, Sirisinha S, Simms ES, Eisen HN. Myeloma proteins as tumor-specific transplantation antigens. Proc Natl Acad Sci U S A 1972; 69:1540–1544.PubMedGoogle Scholar
  11. 11.
    Tao MH, Levy R. Idiotype/granulocyte-macrophage colony-stimulating factor fusion protein as a vaccine for B-cell lymphoma. Nature 1993; 362:755–758.PubMedGoogle Scholar
  12. 12.
    Sirisinha S, Eisen HN. Autoimmune-like antibodies to the ligand-binding sites of myeloma proteins. Proc Natl Acad Sci U S A 1971; 68:3130–3135.PubMedGoogle Scholar
  13. 13.
    Stevenson FK, Gordon J. Immunization with idiotypic immunoglobulin protects against development of B lymphocytic leukemia, but emerging tumor cells can evade antibody attack by modulation. J Immunol 1983; 130:970–973.PubMedGoogle Scholar
  14. 14.
    Kaminski MS, Kitamura K, Maloney DG, Levy R. Idiotype vaccination against murine B cell lymphoma: inhibition of tumor immunity by free idiotype protein. J Immunol 1987; 138:1289–1296.PubMedGoogle Scholar
  15. 15.
    Campbell MJ, Esserman L, Byars NE, Allison AC, Levy R. Idiotype vaccination against murine B cell lymphoma: humoral and cellular requirements for the full expression of antitumor immunity. J Immunol 1990; 145:1029–1036.PubMedGoogle Scholar
  16. 16.
    Kwak L, Campbell MJ, Czerwinski DK, Hart S, Miller RA, Levy R. Induction of immune responses in patients with B-cell lymphoma against the surface-immunoglobulin idiotype expressed by their tumors. N Enal J Med 1992; 327:1209–1215.Google Scholar
  17. 17.
    Hsu FJ, Caspar CB, Czerwinski D, Kwak LW, Liles TM, Syrengelas A, Taidi-Laskowski B, Levy R. Tumor-specific idiotype vaccines in the treatment of patients with B-cell lymphoma: long-term results of a clinical trial. Blood 1997; 89:3129–3135.PubMedGoogle Scholar
  18. 18.
    Nelson EL, Li X, Hsu FJ, Kwak LW, Levy R, Clayberger C, Krensky AM. Tumor-specific, cytotoxic T-lymphocyte response after idiotype vaccination for B-cell, non-Hodgkin’s lymphoma. Blood 1996; 88:580–589.PubMedGoogle Scholar
  19. 19.
    Bendandi M, Gocke CD, Kobrin CB, Benko FA, Sternas LA, Pennington R, Watson T, Reynolds CW, Gause BL, Duffey PL, Jaffe ES, Creekmore SP, Longo DL, Kwak LW. Complete molecular remissions induced by patient-specific vaccination plus granulocyte-monocyte colony-stimulating factor against lymphoma. Nat Med 1999; 5:1171–1177.PubMedGoogle Scholar
  20. 20.
    Barrios Y, Cabrera R, Yanez R, Briz M, Plaza A, Fores R, Fernandez MN, Diaz-Esoada F. Antiidiotypic vaccination in the treatment of low-grade B-cell lymphoma. Haematologica 2002; 87: 400–407.PubMedGoogle Scholar
  21. 21.
    Redfern C, Guthrie TH, Smith MR, Adler M, Holman P, Leonard JP, Levy R, Densmore J, Just R, Rosenfeld F, Wiernik PH, Janakiraman N, Winter JN, Gold D, Bender JF. A phase II trials of Favid [IdKLH] for relapsed indolent non-Hodgkin’s lymphoma [abstract]. Blood 2002; 100:357a.Google Scholar
  22. 22.
    Davis TA, Hsu FJ, Caspar CB, van Beckhoven A, Czerwinski DK, Liles TM, Taidi B, Benike CF, Engleman EG, Levy R. Idiotype vaccination following ABMT can stimulate specific anti-idiotype immune responses in patients with B-cell lymphoma. Biol Blood Marrow Transplant 2001; 7:517–522.PubMedGoogle Scholar
  23. 23.
    Leonard J, Vose J, Timmerman J, Levy R, Ingolia D, Denny D, Coleman M, Kunkel L. Personalized recombinant idiotype vaccination after chemotherapy as initial treatment for mantle cell lymphoma [abstract]. Blood 2002; 100:312b.Google Scholar
  24. 24.
    Holman P, Bashey A, Carrier E, Corringham S, Davis B, Oblon DJ, Chen J, Gold D, Mu X, Ball ED. Immune response to idiotype vaccination following high dose chemotherapy plus autologous stem cell transnlant in indolent and mantle cell lymphoma [abstract]. Blood 2002; 100:315b.Google Scholar
  25. 25.
    Wilson WH, Neelapu S, White T, Hegde U, Pittaluga S, Hakim F, Stetler-Stevenson M, Frye R, Steinberg S, Jaffe ES, Gress R, Staudt L, Janik J, Kwak L. Idiotype vaccine following EPOCHrituximab treatment in untreated mantle cell lymphoma [abstract]. Blood 2002; 100:162a.Google Scholar
  26. 26.
    Timmerman JM, Czerwinski D, Taid B, Levy R. A phase UII trial to evaluate the immunogenicity of recombinant idiotype protein vaccines for the treatment of non-Hodgkin’ s lymphoma [abstract]. Blood 2000; 96:578a.Google Scholar
  27. 27.
    Reddy SA, Cerwinski D, Rajapaksa R, Reinl S, Garger SJ, Cameron T, Barrett J, Novak J, Holtz RB, Levy R. Plant derived single-chain Fv idiotype vaccines are safe and immunogenic in patients with follicular lymphoma: results of a phase I study [abstract]. Blood 2002; 100:163a.Google Scholar
  28. 28.
    Osterroth F, Garbe A, Fisch P, Veelken H. Stimulation of cytotoxic T cells against idiotype immunoglobulin of malignant lymphoma with protein-pulsed or idiotype-transduced dendritic cells. Blood 2000; 95:1342–1349.PubMedGoogle Scholar
  29. 29.
    McCormick AA, Kumagi MH, Hanley K, Turpen TH, Hakim I, Grill LK, Tuse D, Levy S, Levy R. Rapid production of specific vaccines for lymphoma by expression of the tumor-derived single-chain Fv enitones in tobacco plants. Proc Nat Acad Sci U S A 1999; 96:703–708.Google Scholar
  30. 30.
    Grabbe S, Beissert S, Schwartz T, Granstein RD. Dendritic cells as initiators of tumor immune response: a possible strategy for tumor immunotherapy? Immunol Today 1995; 16:117–121.PubMedGoogle Scholar
  31. 31.
    Girolomoni G, Ricciardi-Castagnoli P. Dendritic cells hold promise for immunotherapy. Immunol Today 1997; 118:102–104.Google Scholar
  32. 32.
    Reid CD, Stackpoole A, Meager A, Tikerpae J. Interactions of tumor necrosis factor with granulocytemacrophage colony-stimulating factor and other cytokines in the regulation of dendritic cell growth in vitro from early bipotent CD34+ progenitors in human bone marrow. J Immunol 1992; 149:2681–2688.PubMedGoogle Scholar
  33. 33.
    Sallusto F, Lanzavecchia A. 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 a. J Exp Med 1994; 179:1109–1118.PubMedGoogle Scholar
  34. 34.
    Romani N, Gruner S, Brang D, Kampgen E, Lenz A, Trockenbacher B, Konwalinka G, Fritsch PO, Steinman RM, Schuler G. Proliferating dendritic cell progenitors in human blood. J Exp Med 1994; 180:83–93.PubMedGoogle Scholar
  35. 35.
    Shimizu J, Suda T, Yoshioka T, Kosugi A, Fujiwara H, Hamaoka T. Induction of tumor-specific in vivo protective immunity by immunization with tumor antigen-pulsed antigen-presenting cells. J Immunol 1989; 142:1053–1059.PubMedGoogle Scholar
  36. 36.
    Grabbe S, Bruvers S, Gallo RL, Knisely TL, Nazareno R, Granstein RD. Tumor antigen presentation by murine epidermal cells. J Immunol 1991; 146:3656–3661.PubMedGoogle Scholar
  37. 37.
    Flamand V, Sornasse T, Thielemans K, Demanet C, Bakkus M, Bazin H, Tielemans F, Leo O, Urbain J, Moser M. Murine dendritic cells pulsed in vitro with tumor antigen induce tumor resistance in vivo. Eur J Immunol 1994; 24:605–610.PubMedGoogle Scholar
  38. 38.
    Mayordomo JI, Loftus DJ, Sakamoto H, De Casare CM, Appasamy PM, Lotze MT, Storkus WJ, Appella E, DeLeo AB. Therapy of murine tumors with p53 wild-type and mutant sequence peptidebased vaccines. J Exp Med 1996; 183:1357–1365.PubMedGoogle Scholar
  39. 39.
    Celluzzi CM, Mayordomo JI, Storkus WJ, Lotze MT, Falo LD. Peptide-pulsed dendritic cells induce antigen-specific, CTL-mediated protective tumor immunity. J Exp Med 1996; 183:283–287.PubMedGoogle Scholar
  40. 40.
    Hsu FJ, Benike C, Fagnini F, Liles TM, Czerwinski D, Taidi B, Engleman EG, Levy R. Vaccination of patients with B-cell lymphoma using autologous antigen-pulsed dendritic cells. Nat Med 1996; 2:52–58.PubMedGoogle Scholar
  41. 41.
    Timmerman JM, Czerwinski DK, Davis TA, Hsu FJ, Benike C, Hao ZM, Taidi B, Rajapaksa R, Caspar CB, Okada CY, van Beckhoven A, Liles TM, Engleman EG, Levy R. Idiotype-pulsed dendritic cell vaccination for B-cell lymphoma: clinical and immune responses in 35 patients. Blood 2002; 99:1517–1526.PubMedGoogle Scholar
  42. 42.
    King CA, Spellerberg MB, Zhu D, Rice J, Sahota SS, Thompsett AR, Hamblin TJ, Radl J, Stevenson FK. DNA vaccines with single-chain Fv fused to fragment C of tetanus toxin induce protective immunity against lymphoma and myeloma. Nat Med 1998; 4:1281–1286.PubMedGoogle Scholar
  43. 43.
    Thirdborough ST, Radcliffe JN, Friedmann PS, Stevenson FK. Vaccination with DNA encoding a single-chain TCR fusion protein induces anticlonotypic immunity and protects against T-cell lymphoma. Cancer Res 2002; 62:1757–1760.PubMedGoogle Scholar
  44. 44.
    Timmerman JM, Caspar CB, Lambert SL, Syrengelas S, Levy R. Idiotype-encoding recombinant adenoviruses provide protective immunity against murine B-cell lymphoma. Blood 2001; 97:1370–1377.PubMedGoogle Scholar
  45. 45.
    Syrengelas S, Chen TT, Levy R. DNA immunization induces protective immunity against B-cell lymphoma. Nat Med 1996; 2:1038–1041.PubMedGoogle Scholar
  46. 46.
    Timmerman JM, Singh G, Hermanson G, Hobart P, Czerwinski DK, Taidi B, Rajapaksa R, Caspar CB, van Beckhoven A, Levy R. Immunogenicity of a plasmid DNA vaccine encoding chimeric idiotype in patients with B-cell lymphoma. Cancer Res 2002; 62:5845–5852.PubMedGoogle Scholar
  47. 47.
    Yi Q. Immunoregulatory mechanisms and immunotherapy. In: Mehta J, Singhal S, ed. Myeloma. London: Martin Dunitz, 2002:81–96.Google Scholar
  48. 48.
    Bogen B, Weiss S. Processing and presentation of idiotypes to MHC-restricted T cells. Int Rev Immunol 1993; 10:337–355.PubMedGoogle Scholar
  49. 49.
    Duperray C, Klein B, Dure BG, Zhang Z, Jourdan M, Poncelet P, Favier F, Vincent C, Brochier J, Lenoir G. Phenotypic analysis of human myeloma cell lines. Blood 1989; 73:566–572.PubMedGoogle Scholar
  50. 50.
    Yi Q, Dabadghao S, Österborg A, Bergenbrant S, Holm G. Myeloma bone marrow plasma cells: evidence for their capacity as antigen-presenting cells. Blood 1997; 90:1960–1967.PubMedGoogle Scholar
  51. 51.
    Leo R, Boeker M, Peest D, Hein R, Bartl R, Gessner JE, Selbach J, Wacker G, Deicher H. Multiparameter analyses of normal and malignant human plasma cells: CD38++, CD56+, CD54+, cIg+ is the common phenotype of myeloma cells. Ann Hematol 1992; 64:132–139.PubMedGoogle Scholar
  52. 52.
    Barker HF, Hamilton MS, Ball J, Drew M, Franklin IM. Expression of adhesion molecules IFA-3 and N-CAM on normal and malignant human plasma cells. Br J Haematol 1992; 81:331–335.PubMedGoogle Scholar
  53. 53.
    Westendorf JJ, Ahmann GJ, Armitage RJ, Spriggs MK, Lust JA, Greipp PR, Katzmann JA, Jelinek DF. CD40 expression in malignant plasma cells. Role in stimulation of autocrine IL-6 secretion by a human myeloma cell line. J Immunol 1994; 152:117–128.PubMedGoogle Scholar
  54. 54.
    Pellat-Deceunynck C, Bataille R, Robillard N, Harousseau JL, Rapp MJ, Juge-Morineau N, Wijdenes J, Amiot M. Expression of CD28 and CD40 in human myeloma cells: a comparative study with normal plasma cells. Blood 1994; 84:2597–2603.PubMedGoogle Scholar
  55. 55.
    Hata H, Matsuzaki H, Takeya M, Yoshida M, Sonoki T, Nagasaki A, Kuribayashi N, Kawano F, Takatsuki K. Expression of Fas/Apo-1 (CD95) and apoptosis in tumor cells from patients with plasma cell disorders. Blood 1995; 86:1939–1945.PubMedGoogle Scholar
  56. 56.
    Holm G, Bergenbrant S, Lefvert AK, Yi Q, Österborg A, Mellstedt H. Anti-idiotypic immunity as a potential regulator in mveloma and related diseases. Ann N Y Acad Sci 1991; 636:178–183.PubMedGoogle Scholar
  57. 57.
    Dianzani U, Pileri A, Boccadoro M, Palumbo A, Pioppo P, Bianchi A, Camponi A, Fossati G, Battaglio S, Massaia M. Activated idiotype-reactive cells in suppressor/cytotoxic subpopulations of monoclonal gammopathies: correlation with diagnosis and disease status. Blood 1988; 72:1064–1068.PubMedGoogle Scholar
  58. 58.
    Österborg A, Masucci M, Bergenbrant S, Holm G, Lefvert AK, Mellstedt H. Generation of T cell clones binding F(ab’)2 fragments of idiotypic immunoglobulin in patients with monoclonal gammopathy. Cancer Immunol Immunother 1991; 34:157–162.PubMedGoogle Scholar
  59. 59.
    Bogen B, Malissen B, Haas W. Idiotype-specific T cell clones that recognize syngeneic immunoglobulin fragments in the context of class II molecules. Eur J Immunol 1986; 16:1373–1378.PubMedGoogle Scholar
  60. 60.
    Yi Q, Holm G, Lefvert AK. Idiotype-induced T cell stimulation requires antigen presentation in association with HLA-DR molecules. Clin Exp Immunol 1996; 104:359–365.PubMedGoogle Scholar
  61. 61.
    Yi Q, Bergenbrant S, Österborg A, Ösby E, Östman R, Björkholm M, Holm G, Lefvert AK. T-cell stimulation induced by idiotypes on monoclonal immunoglobulins in patients with monoclonal gammopathies. Scand J Immunol 1993; 38:529–534.PubMedGoogle Scholar
  62. 62.
    Österborg A, Yi Q, Bergenbrant S, Holm G, Lefvert AK, Mellstedt H. Idiotype-specific T cells in multiple myeloma stage I: an evaluation by four different functional tests. Br J Haematol 1995; 89: 110–116.PubMedGoogle Scholar
  63. 63.
    Yi Q, Eriksson I, He W, Holm G, Mellstedt H, Österborg A. Idiotype-specific T lymphocytes in monoclonal gammopathies. Evidence for the presence of CD4+ and CD8+ subsets. Br J Haematol 1997; 96:338–345.PubMedGoogle Scholar
  64. 64.
    Wen YJ, Ling M, Lim SH. Immunogenicity and cross-reactivity with idiotypic IgA of VH CDR3 peptide in multiple mveloma. Br J Haematol 1998; 100:464–468.PubMedGoogle Scholar
  65. 65.
    Fagerberg J, Yi Q, Gigliotti D, Harmenberg U, Ruden U, Persson B, Österborg A, Mellstedt H. T cell epitope mapping of the idiotypic monoclonal IgG heavy and light chains in multiple myeloma. Int J Cancer 1999: 80:671–680.PubMedGoogle Scholar
  66. 66.
    Yi Q, Österborg A, Bergenbrant S, Mellstedt H, Holm G, Lefvert AK. Idiotype-reactive T subsets and tumor load in monoclonal gammopathies. Blood 1995; 86:3043–3049.PubMedGoogle Scholar
  67. 67.
    Walchner M, Wick M. Elevation of CD8+CD11b+Leu-8-T cells is associated with the humoral immunodeficiency in mveloma patients. Clin Exp Immunol 1997; 109:310–316.PubMedGoogle Scholar
  68. 68.
    Wen YJ, Barlogie B, Yi Q. Idiotype-specific cytotoxic T lymphocytes in multiple myeloma: evidence for their capacity to lyse autologous primary tumor cells. Blood 2001; 97:1750–1755.PubMedGoogle Scholar
  69. 69.
    Li Y, Bendandi M, Deng Y, Dunbar C, Munshi N, Jagannath S, Kwak LW, Lyerly HK. Tumor-specific recognition of human myeloma cells by idiotype-induced CD8+ T cells. Blood 2000; 96:2828–2833.PubMedGoogle Scholar
  70. 70.
    Wen YJ, Min R, Tricot G, Barlogie B, Yi Q. Tumor lysate-specific cytotoxic T lymphocytes in multiple myeloma: promising effector cells for immunotherapy. Blood 2002; 99:3280–3285.PubMedGoogle Scholar
  71. 71.
    Dhodapkar MV, Krasovsky J, Olson K. T cells from the tumor microenvironment of patients with progressive myeloma can generate strong, tumor-specific cytolytic responses to autologous, tumorloaded dendritic cells. Proc Natl Acad Sci U S A 2002; 99:13009–13013.PubMedGoogle Scholar
  72. 72.
    Bergenbrant S, Yi Q, Österborg A, Björkholm M, Osby E, Mellstedt H, Lefvert AK, Holm G. Modulation of anti-idiotypic immune response by immunization with the autologous M-component protein in multiple myeloma patients. Br J Haematol 1996; 92:840–846.PubMedGoogle Scholar
  73. 73.
    Österborg A, Yi Q, Henriksson L, Fagerberg J, Bergenbrant S, Jeddi-Tehrani M, Ruden U, Lefvert AK, Holm G, Mellstedt H. Idiotype immunization combined with granulocyte-macrophage colony-stimulating factor in myeloma patients induced type I, major histocompatibility complex-restricted, CD8and CD4-specific T-cell responses. Blood 1998; 91:2459–2466.PubMedGoogle Scholar
  74. 74.
    Massaia M, Borrione P, Battaglio S, Mariani S, Beggiato E, Napoli P, Voena C, Bianchi A, Coscia M, Besostri B, Peola S, Stiefel T, Even J, Novero D, Boccadoro M, Pileri A. Idiotype vaccination in human myeloma: generation of tumor-specific immune responses after high-dose chemotherapy. Blood 1999; 94:673–683.PubMedGoogle Scholar
  75. 75.
    Kwak LW, Taub DD, Duffey PL, Bensinger WI, Bryant EM, Reynolds CW, Longo DL. Transfer of myeloma idiotype-specific immunity from an actively immunised marrow donor. Lancet 1995; 345:1016–1020.PubMedGoogle Scholar
  76. 76.
    Dabadghao S, Bergenbrant S, Anton D, He W, Holm G, Yi Q. Anti-idiotypic T-cell activation in multiple myeloma induced by M-component fragments presented by dendritic cells. Br J Haematol 1998; 100:647–654.PubMedGoogle Scholar
  77. 77.
    Butch AW, Kelly KA, Munshi NC. Dendritic cells derived from multiple myeloma patients efficiently internalize different classes of myeloma protein. Exp Hematol 2001; 29:85–92.PubMedGoogle Scholar
  78. 78.
    Wen YJ, Ling M, Bailey-Wood R, Lim SH. Idiotypic protein-pulsed adherent peripheral blood mononuclear cell-derived dendritic cells prime immune system in multiple myeloma. Clin Cancer Res 1998; 4:957–962.PubMedGoogle Scholar
  79. 79.
    Lim SH, Bailey-Wood R. Idiotypic protein-pulsed dendritic cell vaccination in multiple myeloma. Int J Cancer 1999; 83:215–222.PubMedGoogle Scholar
  80. 80.
    Reichardt VL, Okada CY, Liso A, Beike CJ, Stockerl-Goldstein KE, Engleman EG, Blume KG, Levy R. Idiotype vaccination using dendritic cells after autologous peripheral blood stem cell transplantation for multiple myeloma: a feasibility study. Blood 1999; 93:2411–2419.PubMedGoogle Scholar
  81. 81.
    Liso A, Stockerl-Goldstein KE, Auffermann-Gretzinger S, Beike CJ, Reichardt VL, van Beckhoven A, Rajapaksa R, Engleman EG, Blume KG, Levy R. Idiotype vaccination using dendritic cells after autologous peripheral blood progenitor cell transplantation for multiple myeloma. Biol Blood Marrow Transplant 2000; 6:621–627.PubMedGoogle Scholar
  82. 82.
    Cull G, Durrant L, Stainer C, Haynes A, Russell N. Generation of anti-idiotype immune responses following vaccination with idiotype-protein pulsed dendritic cells in myeloma. Br J Haematol 1999; 107:648–655.PubMedGoogle Scholar
  83. 83.
    Titzer S, Christensen O, Manzke O, Tesch H, Wolf J, Emmerich B, Carsten C, Diehl V, Bohlen H. Vaccination of multiple myeloma patients with idiotype-pulsed dendritic cells: immunological and clinical aspects. Br J Haematol 2000; 108:805–816.PubMedGoogle Scholar
  84. 84.
    Lacy MQ, Geyer S, Wettstein P, Gertz MA, Gastineau DA, Greipp PR, Fonseca R, Dispenzieri A, Lust JA, Witzig TE, Rajkumar SV, Zeldenrust S, Maas M, Iturria N, Weiden P, Kyle RA. Post autologous transplantation consolidation of multiple myeloma with idiotype-pulsed antigen presenting (dendritic) cells (APC8020) is associated with a trend to longer time to progression [abstract]. Blood 2002; 100:425a.Google Scholar
  85. 85.
    Eggert AA, Schreurs MW, Boerman OC, Oyen WJ, de Boer AJ, Punt CJ, Figdor CG, Adema GJ. Biodistribution and vaccine efficiency of murine dendritic cells are dependent on the route of administration. Cancer Res 1999; 59:3340–3345.PubMedGoogle Scholar
  86. 86.
    Morse MA, Coleman RE, Akabani G, Niehaus N, Coleman D, Lyerly HK. Migration of human dendritic cells after injection in patients with metastatic malignancies. Cancer Res 1999; 59:56–58.PubMedGoogle Scholar
  87. 87.
    Fong L, Brockstedt D, Benike C, Wu L, Engleman EG. Dendritic cells injected via different routes induce immunity in cancer patients. J Immunol 2001; 166:4254–4259.PubMedGoogle Scholar
  88. 88.
    Palucka KA, Taquet N, Sanchez-Chapuis F, Gluckman JC. Dendritic cells as the terminal stage of monocyte differentiation. J Immunol 1998; 160:4587–4595.PubMedGoogle Scholar
  89. 89.
    Jonuleit H, Schmitt E, Schuler G, Knop J, Enk AH. Induction of interleukin-10-producing, nonproliferating CD4+ T cells with regulatory properties by repetitive stimulation with allogeneic immature human dendritic cells. J Exp Med 2000; 192:1213–1222.PubMedGoogle Scholar
  90. 90.
    Dhodapkar MV, Steinman RM, Krasovsky J, Munz C, Bhardwaj N. Antigen-specific inhibition of effector T cell function in humans after injection of immature dendritic cells. J Exp Med 2001; 193: 233–238.PubMedGoogle Scholar
  91. 91.
    Yi Q, Desikan R, Barlogie B, Munshi N. Optimising dendritic cell-based immunotherapy in multiple myeloma. Br J Haematol 2002; 117:297–305.PubMedGoogle Scholar
  92. 92.
    Szmania SM, Rosen NA, Gupta SK, Batchu RB, Barlogie B, Cottler-Fox M, Tricot G, Yi Q, van Rhee F. Robust immune responses to vaccination with autologous myeloma tumor lysate loaded dendritic cells [abstract]. Blood 2002; 100:400a.Google Scholar
  93. 93.
    Gong J, Chen D, Kufe D. Induction of antitumor activity by immunization with fusions of dendritic and carcinoma cells. Nat Med 1997; 3:558–561.PubMedGoogle Scholar
  94. 94.
    Wang J, Saffold S, Cao X, Krauss J, Chen W. Eliciting T cell immunity against poorly immunogenic tumors by immunization with dendritic cell-tumor fusion vaccines. J Immunol 1998; 161:5516–5524.PubMedGoogle Scholar
  95. 95.
    Gong J, Chen D, Kashiwaba M, Li Y, Chen L, Takeuchi H, Qu H, Rowse GJ, Gendler SJ, Kufe D. Reversal of tolerance to human MUC1 antigen in MUC1 transgenic mice immunized with fusions of dendritic and carcinoma cells. Proc Natl Acad Sci U S A 1998; 95:6279–6283.PubMedGoogle Scholar
  96. 96.
    Kugler A, Stuhler G, Walden P, Zoller G, Zobywalski A, Brossart P, Trefzer U, Ullrich S, Muller CA, Becker V, Gross AJ, Hemmerlein B, Kanz L, Muller GA, Ringert RH. Regression of human metastatic renal cell carcinoma after vaccination with tumor cell-dendritic cell hybrids. Nat Med 2000; 6:332–336.PubMedGoogle Scholar
  97. 97.
    Gong J, Koido S, Chen D, Tanaka Y, Huang L, Avigan D, Anderson K, Ohno T, Kufe D. Immunization against murine multiple myeloma with fusions of dendritic and plasmacytoma cells is potentiated by interleukin 12. Blood 2002; 99:2512–2517.PubMedGoogle Scholar
  98. 98.
    Grosman DD, Borges V, Vasir D, Wu Z, Anderson K, Richardson P, Munshi N, Kufe D, Avigan D. Dendritic cell (DC)-tumor fusions generated with mature as compared to immature DC potently induce myeloma specific immunity [abstract]. Blood 2002; 100:399a.Google Scholar
  99. 99.
    Zhu D, Rice J, Savelyeva N, Stevenson FK. DNA fusion vaccines against B-cell tumors. Trends Mol Med 2001; 7:566–572.PubMedGoogle Scholar
  100. 100.
    Wendtner CM, Nolte A, Mangold E, Buhmann R, Maass G, Chiorini JA, Winnacker EL, Emmerich B, Kotin RM, Hallek M. Gene transfer of costimulatory molecules B7–1 and B7–2 into human multiple myeloma cells by recombinant adeno-associated virus enhances the cytolytic T-cell response. Gene Ther 1997; 4:726–735.PubMedGoogle Scholar
  101. 101.
    Russell SJ, Dunbar CE. Gene therapy approaches for multiple myeloma. Semin Hematol 2001; 38: 268–275.PubMedGoogle Scholar
  102. 102.
    Trudel S, Li Z, Dodgson C, Nanji S, Wan Y, Voralia M, Hitt M, Fauldie J, Graham FL, Steward AK. Adenovector engineered interleukin-2 expressing autologous plasma cell vaccination after high-dose chemotherapy for multiple myeloma-a phase I study. Leukemia 2001; 15:846–854.PubMedGoogle Scholar
  103. 103.
    Pasquini S, Peralta S, Missiaglia E, Carta L, Lemoine NR. Prime-boost vaccines encoding an intracellular idiotype/GM-CSF fusion protein induce protective cell-mediated immunity in murine pre-B cell leukemia. Gene Ther 2002; 9:503–510.PubMedGoogle Scholar
  104. 104.
    Velders MP, ter Horst SA, Kast WM. Prospect for immunotherapy of acute lymphoblastic leukemia. Leukemia 2001; 15:701–706.PubMedGoogle Scholar
  105. 105.
    Stripecke S, Levine AM, Pullarkat V, Cardoso AA. Immunotherapy with acute leukemia cells modified intn nticen-nrecenting cell c- ex vivo culture and gene transfer methods. Leukemia 2002; 16:1974–1983.PubMedGoogle Scholar
  106. 106.
    Cardoso AA, Seamon MJ, Afonso HM, Chia P, Boussiotis VA, Freeman GJ, Gribben JG, Sallan SE, Nadler LM. Ex vivo generation of human anti-pre-B leukemia-specific autologous cytolytic T cells. Blood 1997; 90:549–561.PubMedGoogle Scholar
  107. 107.
    Vereecque R, Buffenoir G, Preudhomme C, Hetuin D, Bauters F, Fenaux P, Quesnel B. Gene transfer of GM-CSF, CD80 and CD154 cDNA enhances survival in a murine model of acute leukemia with Persistence of a minimal residual diseases. Gene Ther 2000; 7:1312–1316.PubMedGoogle Scholar
  108. 108.
    Cardoso AA, Schultze JL, Boussiotis VA, Freeman GJ, Seamon MJ, Laszlo S, Billet A, Sallan SE, Gribben JG, Nadler LM. Pre-B acute lymphoblastic leukemia cells may induce T-cell anergy to alloantigens. Blood 1996; 88:41–48.PubMedGoogle Scholar
  109. 109.
    Biagi E, Rousseau R, Yvon E, Dotti G, Brenner MK. Bystander transfer of functional human CD40 ligand from gene-modified fibroblasts to leukemia cells. A method suitable for clinical cancer vaccine production [abstract]. Blood 2002; 100:377a.Google Scholar
  110. 110.
    Saudemont A, Vereecque R, Quesnel B. Leukemia dormancy can be induced by gene transfer of IL-12 and CD154 [abstract]. Blood 2002; 100:483b.Google Scholar
  111. 111.
    Rousseau R, Biagi E, Yvon E, Mei Z, Inman S, Rill D, Heslop H, Popat U, Gee A, Krance R, Carrum G, Alcoser P, Rodgers S, Kuehnle I, Margolin J, Brenner MK. Treatment of high-risk acute leukemia with an autologous vaccine expressing transgenic IL-2 and CD4OL [abstract]. Blood 2002; 100:867a.Google Scholar
  112. 112.
    Fujii SI, Shimizu K, Fujimoto K, Kiyokawa T, Tsukamoto A, Sanada I, Kawano F. Treatment of posttransplanted, relapsed patients with hematological malignancies by infusion of HLA-matched, allogeneic-dendritic cells pulsed with irradiated tumor cells and primed T cells. Leuk Lymphoma 2001; 42:357–369.PubMedGoogle Scholar
  113. 113.
    Choudhury BA, Liang JC, Thomas EK, Flores-Romo L, Xie QS, Ahusala K, Sutaria S, Sinha I, Champlin RE, Claxton DF. Dendritic cells derived in vitro from acute myelogenous leukemia cells stimulate autologous, antileukemic T-cell responses. Blood 1999; 93:780–786.PubMedGoogle Scholar
  114. 114.
    Harrison BD, Adams JA, Briggs M, Brereton ML, Yin JA. Stimulation of autologous proliferative and cytotoxic T-cell responses by “leukemic dendritic cells” derived from blast cells in acute myeloid leukemia. Blood 2001; 97:2764–2771.PubMedGoogle Scholar
  115. 115.
    Kohler T, Plettig R, Wetzstein W, Schmitz M, Ritter M, Mohr B, Schaekel U, Ehninger G, Bornhauser M. Cytokine-driven differentiation of blasts from patients with acute myelogenous and lymphoblastic leukemia into dendritic cells. Stem Cells 2000; 18:139–147.PubMedGoogle Scholar
  116. 116.
    Oehler L, Berer A, Kollars M, Keil F, Konig M, Waclavicek M, Haas O, Knapp W, Lechner K, Geissler K. Culture requirements for induction of dendritic cell differentiation in acute myeloid leukemia. Ann Hematol 2000; 79:355–362.PubMedGoogle Scholar
  117. 117.
    Brouwer RE, van der Hoorn M, Kluin-Nelemans HC, van Zelderen-Bhola S, Willemze R, Falkenburg JH. The generation of dendritic-like cells with increased allostimulatory function from acute myeloid leukemia cells of various FAB subclasses. Hum Immunol 2000; 61:565–574.PubMedGoogle Scholar
  118. 118.
    Hicks C, Keoshkerian E, Gaudry L, Lindeman R. CD80 (B7–1) expression on human acute myeloid leukemic cells cultured with GM-CSF, IL-3 and IL-6. Cancer Immunol Immunother 2001; 50: 173–180.PubMedGoogle Scholar
  119. 119.
    Dunussi-Joannopoulos K, Weistein HJ, Nickerson PW, Strom TB, Burakoff SJ, Croop JM, Arceci RJ. Irradiated B7–1 transduced primary acute myelogenous leukemia (AML) cells can be used as therapeutic vaccines in murine AML. Blood 1996; 87:2938–2946.PubMedGoogle Scholar
  120. 120.
    Dunussi-Joannopoulos K, Dranoff G, Weistein HJ, Ferrara JLM, Bierer BE, Croop JM. Gene immunotherapy in murine acute myeloid leukemia: GM-CSF tumor cell vaccines elicit more potent antitumor immunity compared with B7 family and other cytokines. Blood 1998; 91:222–230.PubMedGoogle Scholar
  121. 121.
    Dunussi-Joannopoulos K, Runyon K, Erikson J, Schaub RG, Hawley RG, Leonard JP. Vaccines with interleukin-12-transduced acute myeloid leukemia cells elicit very potent therapeutic and long-lasting protective immunity. Blood 1999; 94:4263–4273.PubMedGoogle Scholar
  122. 122.
    Koya RC, Kasahara N, Pullarkat V, Levine AM, Stripecke R. Transduction of acute myeloid leukemia cells with third generation self-inactivating lentiviral vectors expressing CD80 and GM-CSF: effects on proliferation, differentiation, and stimulation of allogeneic and autologous anti-leukemia immune responses. Leukemia 2002; 16:1645–1654.PubMedGoogle Scholar
  123. 123.
    Spisek R, Chevallier P, Morineau N, Milpied N, Avet-Loiseau H, Harousseau JL, Meflah K, Gregoire M. Induction of leukemia-specific cytotoxic response by cross-presentation of late-apoptotic leukemic blasts by autologous dendritic cells of nonleukemic origin. Cancer Res 2002; 62:2861–2868.PubMedGoogle Scholar
  124. 124.
    Lee JJ, Kook H, Park MS, Nam CE, Nam JH, Chung IJ, Hwang TJ, Kim HJ. Immunotherapy using autologous CD14+ cell-derived dendritic cells pulsed with tumor lysate for acute myeloid leukemia relapse after autologous peripheral blood stem cell transplantation [abstract]. Blood 2002; 100:337a.Google Scholar
  125. 125.
    Galea-Lauri J, Darling D, Mufti G, Harrison P, Farzaneh F. 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 2002; 51:299–310.PubMedGoogle Scholar
  126. 126.
    Claxton DF, McMannis J, Champlin R, Choudhury A. Therapeutic potential of leukemia-derived dendritic cells: preclinical and clinical progress. Crit Rev Immunol 2001; 21:147–155.PubMedGoogle Scholar
  127. 127.
    Smit WM, Rijnbeek M, van Bergen CA, de Paus RA, Vervenne HA, van de Keur M, Willemze R. Generation of dendritic cells expressing bcr-abl from CD34-positive chronic myeloid leukemia precursor cells. Hum Immunol 1997; 53:216–223.PubMedGoogle Scholar
  128. 128.
    Choudhury A, Gajewski JL, Liang JC, Popat U, Claxton DF, Kliche KO, Andreeff M, Champlin RE. Use of leukemic dendritic cells for the generation of antileukemic cellular cytotoxicity against Philadelphia chromosome-positive chronic myelogenous leukemia. Blood 1997; 89:1133–1142.PubMedGoogle Scholar
  129. 129.
    Chen X, Regn S, Raffegerst S, Kolb HJ, Roskrow M. Interferon alpha in combination with GM-CSF induces the differentiation of leukemic antigen-presenting cells that have the capacity to stimulate a specific anti-leukemic cytotoxic T-cell response from patients with chronic myeloid leukemia. Br J Haematol 2000; 111:596–607.PubMedGoogle Scholar
  130. 130.
    Fujii S, Shimizu K, Fujimoto K, Kiyokawa T, Shimomura T, Taniguchi O, Kinoshita M, Kawano F. Analysis of a chronic myelogenous leukemia patient vaccinated with leukemic dendritic cells following autologous peripheral blood stem cell transplantation. Jpn J Cancer Res 1999; 90:1117–1129.PubMedGoogle Scholar
  131. 131.
    Dong R, Cwynarski K, Entwistle A, Marelli-Berg F, Dazzi F, Simpson E, Goldman JM, Melo JV, Lechler RI, Bellantuono I, Ridley A, Lombardi G. Dendritic cells from CML patients have altered actin organization, reduced antigen processing and impaired migration. Blood 2002; prepublished online Dec 27.Google Scholar
  132. 132.
    Eisendle K, Lang A, Eibl B, Nachbaur D, Glassl H, Fiegl M, Thaler J, Gastl G. Phenotypic and functional deficiencies of leukaemic dendritic cells from patients with chronic myeloid leukemia. Br J Haematol 2003; 120:63–73.PubMedGoogle Scholar
  133. 133.
    Bocchia M, Wentworth PA, Southwood S, Sidney J, McGraw K, Scheinberg DA, Sette A. Specific binding of leukemia oncogene fusion protein peptides to HLA class I molecules. Blood 1995; 85:2680–2684.PubMedGoogle Scholar
  134. 134.
    Yotnda P, Firat H, Garcia-Pons F, Garcia Z, Gourru G, Vernant JP, Lemonnier FA, Leblond V, LangladeDemoyen P. Cytotoxic T cell response against the chimeric p210 BCR-ABL protein in patients with chronic myelogenous leukemia. J Clin Invest 1998; 101:2290–2296.PubMedGoogle Scholar
  135. 135.
    Westermann J, Kopp J, Korner I, Richter G, Qin Z, Blankenstein T, Dorken B, Pezzutto A. Bcr/abl+ autologous dendritic cells for vaccination in chronic myeloid leukemia. Bone Marrow Transplant 2000; 25(Suppl 2):546--549.Google Scholar
  136. 136.
    Yasukawa M, Ohminami H, Kaneko S, Yakushijin Y, Nishimura Y, Inokuchi K, Miyakuni T, Nakao S, Kishi K, Kubonishi I, Dan K, Fujita S. CD4+ cytotoxic T-cell clones specific for bcr-abl b3a2 fusion peptide augment colony formation by chronic myelogenous leukemia cells in a b3a2-specific and HLADR-restricted manner. Blood 1998; 92:3355–3361.PubMedGoogle Scholar
  137. 137.
    Yasukawa M, Ohminami H, Kojima K, Hato T, Hasegawa A, Takahashi T, Hirai H, Fujita S. HLA class II-restricted antigen presentation of endogenous bcr-abl fusion protein by chronic myelogenous leukemia-derived dendritic cells to CD4+ T lymphocytes. Blood 2001; 98:1498–1505.PubMedGoogle Scholar
  138. 138.
    Sun JY, Krouse RS, Forman SJ, Senitzer D, Sniecinski I, Chatterjee S, Wong KK. Immunogenicity of a p210(BCR-ABL) fusion domain candidate DNA vaccine targeted to dendritic cells by a recombinant adeno-associated virus vector in vitro. Cancer Res 2002; 62:3175–3183.PubMedGoogle Scholar
  139. 139.
    Osman Y, Takahashi M, Zheng Z, Koike T, Toba K, Liu A, Furukawa T, Aoki S, Aizawa Y. Generation of bcr-abl specific cytotoxic T lymphocytes by using dendritic cells pulsed with bcr-abl (b3a2) peptide: its applicability for donor leukocyte transfusions in marrow grafted CML patients. Leukemia 1999; 13:166–174.PubMedGoogle Scholar
  140. 140.
    Pinilla-Ibarz J, Cathcart K, Korontsvit S, Soignet S, Bocchia M, Caggiano J, Lai L, Jimenez J, Kolitz J, Scheinberg DA. Vaccination of patients with chronic myelogenous leukemia with bcr-abl oncogene breakpoint fusion peptides generates specific immune responses. Blood 2000; 95:1781–1787.PubMedGoogle Scholar
  141. 141.
    Kochenderfer JN, Molldrem JJ. Leukemia vaccines. Curr Oncol Rep 2001; 3:193–200.PubMedGoogle Scholar
  142. 142.
    Dengler R, Munstermann U, al-Batran S, Hausner I, Faderl S, Nerl C, Emmerich B. Immunocytochemical and flow cytometric detection of proteinase 3 (myeloblastin) in normal and leukaemic myeloid cells. Br J Haematol 1995; 89:250–257.PubMedGoogle Scholar
  143. 143.
    Scheibenbogen C, Letsch A, Thiel E, Schmittel A, Mailaender V, Baerwolf S, Nagorsen D, Keilholz U. CD8 T-cell response to Wilms tumor gene product WT1 and proteinase 3 in patients with acute myeloid leukemia. Blood 2002; 100:2132–2137.PubMedGoogle Scholar
  144. 144.
    Molldrem JJ, Dermime S, Parker K, Jiang YZ, Mavroudis D, Hensel N, Fukushima P, Barrett Ai. 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 1996; 88:2450–2457.PubMedGoogle Scholar
  145. 145.
    Molldrem JJ, Lee PP, Wang C, Felio K, Kantarjian HM, Champlin RE, Davis MM. Evidence that specific Tlymphocytes may participate in the elimination of chronic myelogenous leukemia. Nat Med 2000; 6:1018–1023.PubMedGoogle Scholar
  146. 146.
    Molldrem II, Kant S, Lu S, Rios R, Streicher H, Wang C, Giralt S, O’Brien S, Cortes J, Champlin R, Martin T, Wieder E. Peptide vaccination with PR1 elicits active T cell immunity that induces cytogenetic remission in acute myelogenous leukemia [abstract]. Blood 2002; 100:6a.Google Scholar
  147. 147.
    Hu HM, Urba WJ, Fox BA. Gene-modified tumor vaccine with therapeutic potential shifts tumorspecific T cell response from a type 2 to a type 1 cytokine profile. J Immunol 1998; 161:3033–3041.PubMedGoogle Scholar
  148. 148.
    Clark EA, Ledbetter JA. How B and T cells talk to each other. Nature 1994; 367:425–428.PubMedGoogle Scholar
  149. 149.
    Hilbert DM, Shen MY, Rapp UR, Rudikoff S. T cells induce terminal differentiation of transformed B cells to mature plasma cell tumors. Proc Natl Acad Sci U S A 1995; 92:649–653.PubMedGoogle Scholar

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© Humana Press Inc. 2004

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  • Qing Yi

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