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Immunotherapy with acute leukemia cells modified into antigen-presenting cells: ex vivo culture and gene transfer methods

Leukemia volume 16, pages 1974–1983 (2002)Cite this article

Abstract

Adult patients with acute leukemia have, in general, a poor prognosis, with long-term, disease-free survival achieved in only approximately one-third of cases. One of the proposed mechanisms for this poor overall response is the inability of the immune system to detect and eliminate residual malignant leukemia cells, which subsequently serve as a source of leukemic relapse. This review discusses the rationale of immunotherapy for acute leukemia and presents in vitro and in vivo model systems that were devised for pre-B acute lymphocytic leukemia (ALL) and acute myeloid leukemia (AML). New advances in the ex vivo manipulation of acute leukemia cells are presented, which attempt to modify these cells into functional antigen-presenting cells. These cells can then be used as autologous vaccines at the time of minimal residual disease after standard chemotherapy, to stimulate host immune responses against their own leukemia cells. The various approaches toward this aim include incubation of leukemia cells with cytokines or growth factors and gene manipulation of these cells. In particular, ex vivo culture of ALL cells with CD40 ligand, incubation of AML cells with granulocyte–macrophage colony-stimulating factor and interleukin-4 (GM-CSF/IL-4) and lentiviral transduction of ALL and AML cells for expression of immunomodulators (CD80 and GM-CSF) are current approaches under investigation for the development of autologous acute leukemia cell vaccines.

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References

  1. Mayer RJ, Davis RB, Schiffer CA, Berg DT, Powell BL, Schulman P, Omura GA, Moore JO, McIntyre OR, Frei E 3rd . Intensive postremission chemotherapy in adults with acute myeloid leukemia. Cancer and Leukemia Group B N Engl J Med 1994 331: 896–903

    Article  CAS  PubMed  Google Scholar 

  2. Laport GF, Larson RA . Treatment of adult acute lymphoblastic leukemia Semin Oncol 1997 24: 70–82

    CAS  PubMed  Google Scholar 

  3. Cassileth PA, Harrington DP, Appelbaum FR, Lazarus HM, Rowe JM, Paietta E, Willman C, Hurd DD, Bennett JM, Blume KG, Head DR, Wiernik PH . Chemotherapy compared with autologous or allogeneic bone marrow transplantation in the management of acute myeloid leukemia in first remission N Engl J Med 1998 339: 1649–1656

    CAS  PubMed  Google Scholar 

  4. Zhang MJ, Hoelzer D, Horowitz MM, Gale RP, Messerer D, Klein JP, Loffler H, Sobocinski KA, Thiel E, Weisdorf DJ . Long-term follow-up of adults with acute lymphoblastic leukemia in first remission treated with chemotherapy or bone marrow transplantation. The Acute Lymphoblastic Leukemia Working Committee Ann Intern Med 1995 123: 428–431

    CAS  PubMed  Google Scholar 

  5. Foa R, Meloni G, Tosti S, Novarino A, Fenu S, Gavosto F, Mandelli F . Treatment of acute myeloid leukaemia patients with recombinant interleukin 2: a pilot study Br J Haematol 1991 77: 491–496

    CAS  PubMed  Google Scholar 

  6. Meloni G, Foa R, Vignetti M, Guarini A, Fenu S, Tosti S, Tos AG, Mandelli F . Interleukin-2 may induce prolonged remissions in advanced acute myelogenous leukemia Blood 1994 84: 2158–2163

    CAS  PubMed  Google Scholar 

  7. Bilgrami S, Silva M, Cardoso A, Miller KB, Ascensao JL . Immunotherapy with autologous bone-marrow transplantation: rationale and results Exp Hematol 1994 22: 1039–1050

    CAS  PubMed  Google Scholar 

  8. Collins RH Jr, Shpilberg O, Drobyski WR, Porter DL, Giralt S, Champlin R, Goodman SA, Wolff SN, Hu W, Verfaillie C, List A, Dalton W, Ognoskie N, Chetrit A, Antin JH, Nemunaitis J . Donor leukocyte infusions in 140 patients with relapsed malignancy after allogeneic bone marrow transplantation J Clin Oncol 1997 15: 433–444

    PubMed  Google Scholar 

  9. 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 alloantigen Blood 1996 88: 41–48

    CAS  PubMed  Google Scholar 

  10. Zheng Z, Takahashi M, Aoki S, Toba K, Liu A, Osman Y, Takahashi H, Tsukada N, Suzuki N, Nikkuni K, Furukawa T, Koike T, Aizawa Y . Expression patterns of costimulatory molecules on cells derived from human hematological malignancies J Exp Clin Cancer Res 1998 17: 251–258

    CAS  PubMed  Google Scholar 

  11. Costello RT, Mallet F, Sainty D, Maraninchi D, Gastaut JA, Olive D . Regulation of CD80/B7-1 and CD86/B7-2 molecule expression in human primary acute myeloid leukemia and their role in allogenic immune recognition Eur J Immunol 1998 28: 90–103

    CAS  PubMed  Google Scholar 

  12. Schwartz RH . Costimulation of T lymphocytes: the role of CD28, CTLA-4, and B7/BB1 in interleukin-2 production and immunotherapy Cell 1992 71: 1065–1068

    CAS  PubMed  Google Scholar 

  13. Zinkernagel RM, Hengartner H . Regulation of the immune response by antigen Science 2001 293: 251–253

    CAS  PubMed  Google Scholar 

  14. Germain RN . MHC-dependent antigen processing and peptide presentation: providing ligands for T lymphocyte activation Cell 1994 76: 287–299

    CAS  PubMed  Google Scholar 

  15. Pamer E, Cresswell P . Mechanisms of MHC class I-restricted antigen processing Annu Rev Immunol 1998 16: 323–358

    CAS  PubMed  Google Scholar 

  16. Kovacsovics-Bankowski M, Rock KL . A phagosome-to-cytosol pathway for exogenous antigens presented on MHC class I molecules Science 1995 267: 243–246

    CAS  PubMed  Google Scholar 

  17. Watts C . Capture and processing of exogenous antigens for presentation on MHC molecules Annu Rev Immunol 1997 15: 821–850

    CAS  PubMed  Google Scholar 

  18. Gimmi CD, Freeman GJ, Gribben JG, Sugita K, Freedman AS, Morimoto C, Nadler LM . B-cell surface antigen B7 provides a costimulatory signal that induces T cells to proliferate and secrete interleukin 2 Proc Natl Acad Sci USA 1991 88: 6575–6579

    CAS  PubMed  PubMed Central  Google Scholar 

  19. Cardoso AA . Anti-tumor immunity as therapy for human cancer. In: Bronchud MH, Foote MA, Peters WP, Robinson MO (eds) Principles of Molecular Oncology Humana Press: Totowa 2000 359–394

    Google Scholar 

  20. Coyle AJ, Gutierrez-Ramos JC . The expanding B7 superfamily: increasing complexity in costimulatory signals regulating T cell function Nat Immunol 2001 2: 203–209

    CAS  PubMed  Google Scholar 

  21. Boussiotis VA, Freeman GJ, Gribben JG, Nadler LM . The role of B7-1/B7-2:CD28/CLTA-4 pathways in the prevention of anergy, induction of productive immunity and down-regulation of the immune response Immunol Rev 1996 153: 5–26

    CAS  PubMed  Google Scholar 

  22. McAdam AJ, Schweitzer AN, Sharpe AH . The role of B7 co-stimulation in activation and differentiation of CD4+ and CD8+ T cells Immunol Rev 1998 165: 231–247

    CAS  PubMed  Google Scholar 

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

    CAS  PubMed  Google Scholar 

  24. Pulendran B, Banchereau J, Maraskovsky E, Maliszewski C . Modulating the immune response with dendritic cells and their growth factors Trends Immunol 2001 22: 41–47

    CAS  PubMed  Google Scholar 

  25. Ardavin C, Martinez del Hoyo G, Martin P, Anjuere F, Arias CF, Marin AR, Ruiz S, Parrillas V, Hernandez H . Origin and differentiation of dendritic cells Trends Immunol 2001 22: 691–700

    CAS  PubMed  Google Scholar 

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

    CAS  PubMed  Google Scholar 

  27. Epstein MM, Di Rosa F, Jankovic D, Sher A, Matzinger P . Successful T cell priming in B cell-deficient mice J Exp Med 1995 182: 915–922

    CAS  PubMed  Google Scholar 

  28. Schultze JL, Michalak S, Seamon MJ, Dranoff G, Jung K, Daley J, Delgado JC, Gribben JG, Nadler LM . CD40-activated human B cells: an alternative source of highly efficient antigen presenting cells to generate autologous antigen-specific T cells for adoptive immunotherapy J Clin Invest 1997 100: 2757–2765

    CAS  PubMed  PubMed Central  Google Scholar 

  29. Ghia P, ten Boekel E, Rolink AG, Melchers F . B-cell development: a comparison between mouse and man Immunol Today 1998 19: 480–485

    CAS  PubMed  Google Scholar 

  30. LeBien TW . Fates of human B-cell precursors Blood 2000 96: 9–23

    CAS  PubMed  Google Scholar 

  31. McCulloch EA . Stem cells in normal and leukemic hemopoiesis (Henry Stratton Lecture, 1982) Blood 1983 62: 1–13

    CAS  PubMed  Google Scholar 

  32. Cardoso AA, Seamon MJ, Afonso HM, Ghia 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

    CAS  PubMed  Google Scholar 

  33. Matsumoto K, Anasetti C . The role of T cell costimulation by CD80 in the initiation and maintenance of the immune response to human leukemia Leuk Lymphoma 1999 35: 427–435

    CAS  PubMed  Google Scholar 

  34. Hirano N, Takahashi T, Ohtake S, Hirashima K, Emi N, Saito K, Hirano M, Shinohara K, Takeuchi M, Taketazu F, Tsunoda S, Ogura M, Omine M, Saito T, Yazaki Y, Ueda R, Hirai H . Expression of costimulatory molecules in human leukemias Leukemia 1996 10: 1168–1176

    CAS  PubMed  Google Scholar 

  35. Bruserud O . Acute myelogenous leukemia blasts as accessory cells during T lymphocyte activation: possible implications for future therapeutic strategies Leukemia 1999 13: 1175–1187

    CAS  PubMed  Google Scholar 

  36. Sotomayor EM, Borrello I, Rattis FM, Cuenca AG, Abrams J, Staveley-O'Carroll K, Levitsky HI . Cross-presentation of tumor antigens by bone marrow-derived antigen-presenting cells is the dominant mechanism in the induction of T-cell tolerance during B-cell lymphoma progression Blood 2001 98: 1070–1077

    CAS  PubMed  Google Scholar 

  37. Velders MP, ter Horst SA, Kast WM . Prospect for immunotherapy of acute lymphoblastic leukemia Leukemia 2001 15: 701–706

    CAS  PubMed  Google Scholar 

  38. Manzke O, Berthold F, Huebel K, Tesch H, Diehl V, Bohlen H . CD3 × CD19 bispecific antibodies and CD28 bivalent antibodies enhance T-cell reactivity against autologous leukemic cells in pediatric B-ALL bone marrow Int J Cancer 1999 80: 715–722

    CAS  PubMed  Google Scholar 

  39. Montagna D, Maccario R, Locatelli F, Rosti V, Yang Y, Farness P, Moretta A, Comoli P, Montini E, Vitiello A . Ex vivo priming for long-term maintenance of antileukemia human cytotoxic T cells suggests a general procedure for adoptive immunotherapy Blood 2001 98: 3359–3366

    CAS  PubMed  Google Scholar 

  40. Banchereau J, Bazan F, Blanchard D, Briere F, Galizzi JP, van Kooten C, Liu YJ, Rousset F, Saeland S . The CD40 antigen and its ligand Annu Rev Immunol 1994 12: 881–922

    CAS  PubMed  Google Scholar 

  41. Cardoso AA, Veiga JP, Ghia P, Afonso HM, Haining WN, Sallan SE, Nadler LM . Adoptive T-cell therapy for B-cell acute lymphoblastic leukemia: preclinical studies Blood 1999 94: 3531–3540

    CAS  PubMed  Google Scholar 

  42. Ghia P, Transidico P, Veiga JP, Schaniel C, Sallusto F, Matsushima K, Sallan SE, Rolink AG, Mantovani A, Nadler LM, Cardoso AA . Chemoattractants MDC and TARC are secreted by malignant B-cell precursors following CD40 ligation and support the migration of leukemia-specific T cells Blood 2001 98: 533–540

    CAS  PubMed  Google Scholar 

  43. 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

    CAS  PubMed  Google Scholar 

  44. Choudhury BA, Liang JC, Thomas EK, Flores-Romo L, Xie QS, Agusala 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

    CAS  PubMed  Google Scholar 

  45. 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

    CAS  PubMed  Google Scholar 

  46. 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 alpha J Exp Med 1994 179: 1109–1118

    CAS  PubMed  Google Scholar 

  47. 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

    CAS  PubMed  Google Scholar 

  48. Hicks C, Keoshkerian E, Gaudry L, Lindeman R . CD80 (B7-1) expression on human acute myeloid leukaemic cells cultured with GM-CSF, IL-3 and IL-6 Cancer Immunol Immunother 2001 50: 173–180

    CAS  PubMed  Google Scholar 

  49. Stripecke R, Skelton DC, Gruber T, Afar D, Pattengale PK, Witte ON, Kohn DB . Immune response to Philadelphia chromosome-positive acute lymphoblastic leukemia induced by expression of CD80, interleukin 2, and granulocyte–macrophage colony-stimulating factor Hum Gene Ther 1998 9: 2049–2062

    CAS  PubMed  Google Scholar 

  50. Goga A, McLaughlin J, Afar DE, Saffran DC, Witte ON . Alternative signals to RAS for hematopoietic transformation by the BCR- ABL oncogene Cell 1995 82: 981–988

    CAS  PubMed  Google Scholar 

  51. Stripecke R, Skelton DC, Pattengale PK, Shimada H, Kohn DB . Combination of CD80 and granulocyte–macrophage colony-stimulating factor coexpression by a leukemia cell vaccine: preclinical studies in a murine model recapitulating Philadelphia chromosome-positive acute lymphoblastic leukemia Hum Gene Ther 1999 10: 2109–2122

    CAS  PubMed  Google Scholar 

  52. Dunussi-Joannopoulos K, Weinstein 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

    CAS  PubMed  Google Scholar 

  53. Dunussi-Joannopoulos K, Krenger W, Weinstein HJ, Ferrara JL, Croop JM . CD8+ T cells activated during the course of murine acute myelogenous leukemia elicit therapeutic responses to late B7 vaccines after cytoreductive treatment Blood 1997 89: 2915–2924

    CAS  PubMed  Google Scholar 

  54. Dunussi-Joannopoulos KDG, Weinstein HJ, Ferrara JL, Bierer BE, Croop JM . 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 1998 91: 222–230

    CAS  PubMed  Google Scholar 

  55. Dunussi-Joannopoulos K, Runyon K, Erickson 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

    CAS  PubMed  Google Scholar 

  56. Matulonis UA, Dosiou C, Lamont C, Freeman GJ, Mauch P, Nadler LM, Griffin JD . Role of B7-1 in mediating an immune response to myeloid leukemia cells Blood 1995 85: 2507–2515

    CAS  PubMed  Google Scholar 

  57. Matulonis U, Dosiou C, Freeman G, Lamont C, Mauch P, Nadler LM, Griffin JD . B7-1 is superior to B7-2 costimulation in the induction and maintenance of T cell-mediated antileukemia immunity. Further evidence that B7-1 and B7-2 are functionally distinct J Immunol 1996 156: 1126–1131

    CAS  PubMed  Google Scholar 

  58. Nakazaki Y, Tani K, Lin ZT, Sumimoto H, Hibino H, Tanabe T, Wu MS, Izawa K, Hase H, Takahashi S, Tojo A, Azuma M, Hamada H, Mori S, Asano S . Vaccine effect of granulocyte–macrophage colony-stimulating factor or CD80 gene-transduced murine hematopoietic tumor cells and their cooperative enhancement of antitumor immunity Gene Therapy 1998 5: 1355–1362

    CAS  PubMed  Google Scholar 

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

    CAS  PubMed  Google Scholar 

  60. 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 disease Gene Therapy 2000 7: 1312–1316

    CAS  PubMed  Google Scholar 

  61. Mascarenhas L, Stripecke R, Case SS, Xu D, Weinberg KI, Kohn DB . Gene delivery to human B-precursor acute lymphoblastic leukemia cells Blood 1998 92: 3537–3545

    CAS  PubMed  Google Scholar 

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

    CAS  PubMed  Google Scholar 

  63. Roddie PH, Paterson T, Turner ML . Gene transfer to primary acute myeloid leukaemia blasts and myeloid leukaemia cell lines Cell Mol Ther 2000 6: 127–134

    CAS  Google Scholar 

  64. Dilloo D, Rill D, Entwistle C, Boursnell M, Zhong W, Holden W, Holladay M, Inglis S, Brenner M . A novel herpes vector for the high-efficiency transduction of normal and malignant human hematopoietic cells Blood 1997 89: 119–127

    CAS  PubMed  Google Scholar 

  65. Mutis T, Schrama E, Melief CJ, Goulmy E . CD80-transfected acute myeloid leukemia cells induce primary allogeneic T-cell responses directed at patient specific minor histocompatibility antigens and leukemia-associated antigens Blood 1998 92: 1677–1684

    CAS  PubMed  Google Scholar 

  66. Anderson R, Macdonald I, Corbett T, Hacking G, Lowdell MW, Prentice HG . Construction and biological characterization of an interleukin-12 fusion protein (Flexi-12): delivery to acute myeloid leukemic blasts using adeno-associated virus Hum Gene Ther 1997 8: 1125–1135

    CAS  PubMed  Google Scholar 

  67. Wattel E, Vanrumbeke M, Abina MA, Cambier N, Preudhomme C, Haddada H, Fenaux P . Differential efficacy of adenoviral mediated gene transfer into cells from hematological cell lines and fresh hematological malignancies Leukemia 1996 10: 171–174

    CAS  PubMed  Google Scholar 

  68. Howard DS, Rizzierri DA, Grimes B, Upchurch D, Phillips GL, Stewart AK, Yannelli JR, Jordan CT . Genetic manipulation of primitive leukemic and normal hematopoietic cells using a novel method of adenovirus-mediated gene transfer Leukemia 1999 13: 1608–1616

    CAS  PubMed  Google Scholar 

  69. Yang Y, Jooss KU, Su Q, Ertl HC, Wilson JM . Immune responses to viral antigens versus transgene product in the elimination of recombinant adenovirus-infected hepatocytes in vivo Gene Therapy 1996 3: 137–144

    PubMed  Google Scholar 

  70. Jooss K, Ertl HC, Wilson JM . Cytotoxic T-lymphocyte target proteins and their major histocompatibility complex class I restriction in response to adenovirus vectors delivered to mouse liver J Virol 1998 72: 2945–2954

    CAS  PubMed  PubMed Central  Google Scholar 

  71. Naldini L, Blomer U, Gallay P, Ory D, Mulligan R, Gage FH, Verma IM, Trono D . In vivo gene delivery and stable transduction of nondividing cells by a lentiviral vector Science 1996 272: 263–267

    CAS  PubMed  Google Scholar 

  72. Case SS, Price MA, Jordan CT, Yu XJ, Wang L, Bauer G, Haas DL, Xu D, Stripecke R, Naldini L, Kohn DB, Crooks GM . Stable transduction of quiescent CD34(+)CD38(−) human hematopoietic cells by HIV-1-based lentiviral vectors Proc Natl Acad Sci USA 1999 96: 2988–2993

    CAS  PubMed  PubMed Central  Google Scholar 

  73. Weinberg JB, Matthews TJ, Cullen BR, Malim MH . Productive human immunodeficiency virus type 1 (HIV-1) infection of nonproliferating human monocytes J Exp Med 1991 174: 1477–1482

    CAS  PubMed  Google Scholar 

  74. Bukrinsky MI, Haggerty S, Dempsey MP, Sharova N, Adzhubel A, Spitz L, Lewis P, Goldfarb D, Emerman M, Stevenson M . A nuclear localization signal within HIV-1 matrix protein that governs infection of non-dividing cells Nature 1993 365: 666–669

    CAS  PubMed  Google Scholar 

  75. Planken EV, Willemze R, Kluin-Nelemans JC . The role of the CD40 antigen on malignant B cells Leuk Lymphoma 1996 22: 229–235

    CAS  PubMed  Google Scholar 

  76. Stripecke R, Cardoso AA, Pepper KA, Skelton DC, Yu XJ, Mascarenhas L, Weinberg KI, Nadler LM, Kohn DB . Lentiviral vectors for efficient delivery of CD80 and granulocyte–macrophage colony-stimulating factor in human acute lymphoblastic leukemia and acute myeloid leukemia cells to induce antileukemic immune responses Blood 2000 96: 1317–1326

    CAS  PubMed  Google Scholar 

  77. Zufferey R, Nagy D, Mandel RJ, Naldini L, Trono D . Multiply attenuated lentiviral vector achieves efficient gene delivery in vivo Nat Biotechnol 1997 15: 871–875

    CAS  PubMed  Google Scholar 

  78. 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

    CAS  PubMed  Google Scholar 

  79. Sievers EL, Linenberger M . Mylotarg: antibody-targeted chemotherapy comes of age Curr Opin Oncol 2001 13: 522–527

    CAS  PubMed  Google Scholar 

  80. Boyer MW, Vallera DA, Taylor PA, Gray GS, Katsanis E, Gorden K, Orchard PJ, Blazar BR . 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 1997 89: 3477–3485

    CAS  PubMed  Google Scholar 

  81. Blazar BR, Taylor PA, Boyer MW, Panoskaltsis-Mortari A, Allison JP, Vallera DA . CD28/B7 interactions are required for sustaining the graft-versus-leukemia effect of delayed post-bone marrow transplantation splenocyte infusion in murine recipients of myeloid or lymphoid leukemia cells J Immunol 1997 159: 3460–3473

    CAS  PubMed  Google Scholar 

  82. Bonnet D, Warren EH, Greenberg PD, Dick JE, Riddell SR . CD8(+) minor histocompatibility antigen-specific cytotoxic T lymphocyte clones eliminate human acute myeloid leukemia stem cells Proc Natl Acad Sci USA 1999 96: 8639–8644

    CAS  PubMed  PubMed Central  Google Scholar 

  83. Zufferey R, Dull T, Mandel RJ, Bukovsky A, Quiroz D, Naldini L, Trono D . Self-inactivating lentivirus vector for safe and efficient in vivo gene delivery J Virol 1998 72: 9873–9880

    CAS  PubMed  PubMed Central  Google Scholar 

  84. Dull T, Zufferey R, Kelly M, Mandel RJ, Nguyen M, Trono D, Naldini L . A third-generation lentivirus vector with a conditional packaging system J Virol 1998 72: 8463–8471

    CAS  PubMed  PubMed Central  Google Scholar 

  85. Sutton RE, Wu HT, Rigg R, Bohnlein E, Brown PO . Human immunodeficiency virus type 1 vectors efficiently transduce human hematopoietic stem cells J Virol 1998 72: 5781–5788

    CAS  PubMed  PubMed Central  Google Scholar 

  86. Yotnda P, Mintz P, Grigoriadou K, Lemonnier F, Vilmer E, Langlade-Demoyen P . Analysis of T-cell defects in the specific immune response against acute lymphoblastic leukemia cells Exp Hematol 1999 27: 1375–1383

    CAS  PubMed  Google Scholar 

  87. Mutis T, Verdijk R, Schrama E, Esendam B, Brand A, Goulmy E . Feasibility of immunotherapy of relapsed leukemia with ex vivo-generated cytotoxic T lymphocytes specific for hematopoietic system-restricted minor histocompatibility antigens Blood 1999 93: 2336–2341

    CAS  PubMed  Google Scholar 

  88. Dolstra H, Fredrix H, Maas F, Coulie PG, Brasseur F, Mensink E, Adema GJ, de Witte TM, Figdor CG, van de Wiel-van Kemenade E . A human minor histocompatibility antigen specific for B cell acute lymphoblastic leukemia J Exp Med 1999 189: 301–308

    CAS  PubMed  PubMed Central  Google Scholar 

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

    CAS  PubMed  Google Scholar 

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

    CAS  PubMed  Google Scholar 

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Acknowledgements

RS was supported by Special Fellow Award from the Leukemia and Lymphoma Society (3002-00), by a Howard Temin Award from the National Cancer Institute (K01-CA87864-01), a short-term fellowship from the German Research Council (DFG-STR 472/2-10) and research grants from Concern Foundation and Stop Cancer. VP was supported by a pilot grant from the American Cancer Society (IRG-58-007-42). AAC is supported by NIH PO1 grant (CA6848), the Leukemia Research Foundation and the Fundação para a Ciência e a Tecnologia (Portugal).

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  1. Institute for Genetic Medicine, University of Southern California, Los Angeles, CA, USA

    R Stripecke

  2. Division of Hematology, Norris Comprehensive Cancer Center Keck School of Medicine, University of Southern California, Los Angeles, CA, USA

    R Stripecke, AM Levine & V Pullarkat

  3. Department of Adult Oncology, Dana Farber Cancer Institute, Harvard Medical School, Boston, MA, USA

    AA Cardoso

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Stripecke, R., Levine, A., Pullarkat, V. et al. Immunotherapy with acute leukemia cells modified into antigen-presenting cells: ex vivo culture and gene transfer methods. Leukemia 16, 1974–1983 (2002). https://doi.org/10.1038/sj.leu.2402701

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