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Understanding and Enhancing the Graft-Versus-Leukemia Effect After Hematopoietic Stem Cell Transplantation

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Hematopoietic Stem Cell Transplantation

Part of the book series: Cancer Treatment and Research ((CTAR,volume 144))

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References

  1. Barnes DW, Corp MJ, Loutit JF, Neal FE. Treatment of murine leukemia with X-rays and homologous bone marrow. Br Med J. 1956;2:626–27.

    Article  PubMed  CAS  Google Scholar 

  2. Thomas E, Storb R, Clift RA, et al. Bone-marrow transplantation (first of two parts). N Engl J Med. 1975;292:832–43.

    Article  PubMed  CAS  Google Scholar 

  3. Thomas ED, Storb R, Clift RA, et al. Bone-marrow transplantation (second of two parts). N Engl J Med. 1975;292:895–902.

    Article  PubMed  CAS  Google Scholar 

  4. Weiden PL, Flournoy N, Thomas ED, et al. Antileukemic effect of graft-versus-host disease in human recipients of allogeneic-marrow grafts. N Engl J Med. 1979;300:1068–73.

    Article  PubMed  CAS  Google Scholar 

  5. Weiden PL, Sullivan KM, Flournoy N, et al. Antileukemic effect of chronic graft-versus-host disease: contribution to improved survival after allogeneic marrow transplantation. N Engl J Med. 1981;304:1529–33.

    Article  PubMed  CAS  Google Scholar 

  6. Butterini A, Bortin MM, Gale RP. Graft-versus-leukemia following bone marrow transplantation. Bone Marrow Transplantation. 1987;2:233–42.

    Google Scholar 

  7. Fefer A, Sullivan KM, Weiden P, et al. Graft versus leukemia effect in man: the relapse rate of acute leukemia is lower after allogeneic than after syngeneic marrow transplantation. Prog Clin Biol Res. 1987;244:401–8.

    PubMed  CAS  Google Scholar 

  8. Gale RP, Horowitz MM. Graft-versus-leukemia in bone marrow transplantation. The Advisory Committee of the International Bone Marrow Transplant Registry. Bone Marrow Transplant. 1990;6 Suppl 1:94–7.

    PubMed  Google Scholar 

  9. Horowitz MM, Gale RP, Sondel PM, et al. Graft-versus-leukemia reactions after bone marrow transplantation. Blood 1990;75:555–62.

    PubMed  CAS  Google Scholar 

  10. Korngold R, Leighton C, Manser T. Graft-versus-myeloid leukemia responses following syngeneic and allogeneic bone marrow transplantation. Transplantation 1994;58(3):278–87.

    PubMed  CAS  Google Scholar 

  11. Marmont AM, Horowitz MM, Gale RP, et al. T-cell depletion of HLA-identical transplants in leukemia. Blood 1991;78(8):2120–30.

    PubMed  CAS  Google Scholar 

  12. Sullivan KM, Storb R, Buckner CD, et al. Graft-versus-host disease as adoptive immunotherapy in patients with advanced hematologic neoplasms. N Engl J Med. 1989;320(13):828–34.

    Article  PubMed  CAS  Google Scholar 

  13. Kolb HJ, Mittermuller J, Clemm C, et al. Donor leukocyte transfusions for treatment of recurrent chronic myelogenous leukemia in marrow transplant patients. Blood 1990;76(12):2462–5.

    PubMed  CAS  Google Scholar 

  14. Johnson BD, Drobyski WR, Truitt RL. Delayed infusion of normal donor cells after MHC-matched bone marrow transplantation provides an antileukemia reaction without graft-versus-host disease. Bone Marrow Transplant. 1993;11(4):329–36.

    PubMed  CAS  Google Scholar 

  15. Kolb HJ, Gunther W, Schumm M, Holler E, Wilmanns W, Thierfelder S. Adoptive immunotherapy in canine chimeras. Transplantation 1997;63(3):430–6.

    Article  PubMed  CAS  Google Scholar 

  16. Collins RH Jr, Goldstein S, Giralt S, et al. Donor leukocyte infusions in acute lymphocytic leukemia. Bone Marrow Transplant. 2000;26:511–6.

    Article  PubMed  Google Scholar 

  17. Collins RH Jr, Shpilberg O, Drobyski WR, et al. Donor leukocyte infusions in 140 patients with relapsed malignancy after allogeneic bone marrow transplantation. J Clin Oncol. 1997;15:433–44.

    PubMed  Google Scholar 

  18. Kolb HJ, Schattenberg A, Goldman JM, et al. Graft-versus-leukemia effect of donor lymphocyte transfusions in marrow grafted patients. Blood 1995;86:2041–50.

    PubMed  CAS  Google Scholar 

  19. Peggs KS, Mackinnon S. Cellular therapy: donor lymphocyte infusion. Curr Opin Hematol. 2001;8:349–54.

    Article  PubMed  CAS  Google Scholar 

  20. Porter DL, Collins RH Jr, Shpilberg O, et al. Long-term follow-up of patients who achieved complete remission after donor leukocyte infusions. Biol Blood Marrow Transplant. 1999;5:253–61.

    Article  PubMed  CAS  Google Scholar 

  21. Lokhorst HM, Schattenberg A, Cornelissen JJ, et al. Donor lymphocyte infusions for relapsed multiple myeloma after allogeneic stem-cell transplantation: predictive factors for response and long-term outcome. J Clin Oncol. 2000;18:3031–7.

    PubMed  CAS  Google Scholar 

  22. Levine JE, Braun T, Penza SL, et al. Prospective trial of chemotherapy and donor leukocyte infusions for relapse of advanced myeloid malignancies after allogeneic stem-cell transplantation. J Clin Oncol. 2002;20:405–12.

    Article  PubMed  CAS  Google Scholar 

  23. Keil F, Haas OA, Fritsch G, et al. Donor leukocyte infusion for leukemic relapse after allogeneic marrow transplantation: lack of residual donor hematopoiesis predicts aplasia. Blood 1997;89:3113–7.

    PubMed  CAS  Google Scholar 

  24. Flowers ME, Leisenring W, Beach K, et al. Granulocyte colony-stimulating factor given to donors before apheresis does not prevent aplasia in patients treated with donor leukocyte infusion for recurrent chronic myeloid leukemia after bone marrow transplantation. Biol Blood Marrow Transplant. 2000;6:321–6.

    Article  PubMed  CAS  Google Scholar 

  25. Mackinnon S, Papadopoulos EB, Carabasi MH, et al. Adoptive immunotherapy evaluating escalating doses of donor leukocytes for relapse of chronic myeloid leukemia after bone marrow transplantation: separation of graft-versus-leukemia responses from graft-versus-host disease. Blood 1995;86:1261–8.

    PubMed  CAS  Google Scholar 

  26. Bonini C, Ferrari G, Verzeletti S, et al. HSV-TK gene transfer into donor lymphocytes for control of allogeneic graft-versus-leukemia. Science 1997;276:1719–24.

    Article  PubMed  CAS  Google Scholar 

  27. Bonini C, Bondanza A, Perna SK, et al. The suicide gene therapy challenge: how to improve a successful gene therapy approach. Mol Ther. 2007;15:1248–52.

    Article  PubMed  CAS  Google Scholar 

  28. Berger C, Flowers ME, Warren EH, Riddell SR. Analysis of transgene-specific immune responses that limit the in vivo persistence of adoptively transferred HSV-TK-modified donor T cells after allogeneic hematopoietic cell transplantation. Blood 2006;107: 2294–302.

    Article  PubMed  CAS  Google Scholar 

  29. Riddell SR, Elliott M, Lewinsohn DA, et al. T-cell mediated rejection of gene-modified HIV-specific cytotoxic T lymphocytes in HIV-infected patients. Nat Med. 1996;2:216–23.

    Article  PubMed  CAS  Google Scholar 

  30. Berger C, Blau CA, Huang ML, et al. Pharmacologically regulated Fas-mediated death of adoptively transferred T cells in a nonhuman primate model. Blood 2004;103:1261–9.

    Article  PubMed  CAS  Google Scholar 

  31. Straathof KC, Pule MA, Yotnda P, et al. An inducible caspase 9 safety switch for T-cell therapy. Blood 2005;105:4247–54.

    Article  PubMed  CAS  Google Scholar 

  32. Tey SK, Dotti G, Rooney CM, Heslop HE, Brenner MK. Inducible caspase 9 suicide gene to improve the safety of allodepleted T cells after haploidentical stem cell transplantation. Biol Blood Marrow Transplant. 2007;13:913–24.

    Article  PubMed  CAS  Google Scholar 

  33. Hsu KC, Gooley T, Malkki M, et al. KIR ligands and prediction of relapse after unrelated donor hematopoietic cell transplantation for hematologic malignancy. Biol Blood Marrow Transplant. 2006;12:828–36.

    Article  PubMed  CAS  Google Scholar 

  34. Hsu KC, Keever-Taylor CA, Wilton A, et al. Improved outcome in HLA-identical sibling hematopoietic stem-cell transplantation for acute myelogenous leukemia predicted by KIR and HLA genotypes. Blood 2005;105:4878–84.

    Article  PubMed  CAS  Google Scholar 

  35. Miller JS, Cooley S, Parham P, et al. Missing KIR ligands are associated with less relapse and increased graft-versus-host disease (GVHD) following unrelated donor allogeneic HCT. Blood 2007;109:5058–61.

    Article  PubMed  CAS  Google Scholar 

  36. Ruggeri L, Capanni M, Urbani E, et al. Effectiveness of donor natural killer cell alloreactivity in mismatched hematopoietic transplants. Science 2002;295:2097–100.

    Article  PubMed  CAS  Google Scholar 

  37. Bleakley M, Riddell SR. Molecules and mechanisms of the graft-versus-leukaemia effect. Nat Rev Cancer. 2004;4:371–80.

    Article  PubMed  CAS  Google Scholar 

  38. Falkenburg JH, van de Corput L, Marijt EW, Willemze R. Minor histocompatibility antigens in human stem cell transplantation. Exp Hematol. 2003;31:743–51.

    Article  PubMed  CAS  Google Scholar 

  39. Molldrem JJ, Lee PP, Wang C, et al. Evidence that specific T lymphocytes may participate in the elimination of chronic myelogenous leukemia. Nat Med. 2000;6:1018–23.

    Article  PubMed  CAS  Google Scholar 

  40. Rezvani K, Yong AS, Savani BN, et al. Graft-versus-leukemia effects associated with detectable Wilms tumor-1 specific T lymphocytes after allogeneic stem-cell transplantation for acute lymphoblastic leukemia. Blood 2007;110:1924–32.

    Article  PubMed  CAS  Google Scholar 

  41. Timonen T, Ortaldo JR, Herberman RB. Characteristics of human large granular lymphocytes and relationship to natural killer and K cells. J Exp Med. 1981;153:569–82.

    Article  PubMed  CAS  Google Scholar 

  42. Miller JS. The biology of natural killer cells in cancer, infection, and pregnancy. Exp Hematol. 2001;29:1157–68.

    Article  PubMed  CAS  Google Scholar 

  43. Robertson MJ, Ritz J. Biology and clinical relevance of human natural killer cells. Blood 1990;76:2421–38.

    PubMed  CAS  Google Scholar 

  44. Herberman RB, Ortaldo JR. Natural killer cells: their roles in defenses against disease. Science 1981;214:24–30.

    Article  PubMed  CAS  Google Scholar 

  45. Uhrberg M, Valiante NM, Shum BP, et al. Human diversity in killer cell inhibitory receptor genes. Immunity 1997;7:753–63.

    Article  PubMed  CAS  Google Scholar 

  46. Lazetic S, Chang C, Houchins JP, Lanier LL, Phillips JH. Human natural killer cell receptors involved in MHC class I recognition are disulfide-linked heterodimers of CD94 and NKG2 subunits. J Immunol. 1996;157:4741–5.

    PubMed  CAS  Google Scholar 

  47. Braud VM, Allan DS, O’Callaghan CA, et al. HLA-E binds to natural killer cell receptors CD94/NKG2A, B and C. Nature 1998;391:795–9.

    Article  PubMed  CAS  Google Scholar 

  48. Borrego F, Masilamani M, Marusina AI, Tang X, Coligan JE. The CD94/NKG2 family of receptors: from molecules and cells to clinical relevance. Immunol Res. 2006;35:263–78.

    Article  PubMed  CAS  Google Scholar 

  49. Kirwan SE, Burshtyn DN. Regulation of natural killer cell activity. Curr Opin Immunol. 2007;19:46–54.

    Article  PubMed  CAS  Google Scholar 

  50. Miller JS, Soignier Y, Panoskaltsis-Mortari A, et al. Successful adoptive transfer and in vivo expansion of human haploidentical NK cells in patients with cancer. Blood 2005;105:3051–7.

    Article  PubMed  CAS  Google Scholar 

  51. Miller JS, Tessmer-Tuck J, Pierson BA, et al. Low dose subcutaneous interleukin-2 after autologous transplantation generates sustained in vivo natural killer cell activity. Biol Blood Marrow Transplant. 1997;3:34–44.

    PubMed  CAS  Google Scholar 

  52. Savani BN, Mielke S, Adams S, et al. Rapid natural killer cell recovery determines outcome after T-cell-depleted HLA-identical stem cell transplantation in patients with myeloid leukemias but not with acute lymphoblastic leukemia. Leukemia 2007;21:2145–52.

    Article  PubMed  CAS  Google Scholar 

  53. Exley M, Garcia J, Wilson SB, et al. CD1d structure and regulation on human thymocytes, peripheral blood T cells, B cells and monocytes. Immunology 2000;100:37–47.

    Article  PubMed  CAS  Google Scholar 

  54. Pulendran B, Lingappa J, Kennedy MK, et al. Developmental pathways of dendritic cells in vivo: distinct function, phenotype, and localization of dendritic cell subsets in FLT3 ligand-treated mice. J Immunol. 1997;159:2222–31.

    PubMed  CAS  Google Scholar 

  55. Spada FM, Borriello F, Sugita M, Watts GF, Koezuka Y, Porcelli SA. Low expression level but potent antigen presenting function of CD1d on monocyte lineage cells. Eur J Immunol. 2000;30:3468–77.

    Article  PubMed  CAS  Google Scholar 

  56. Fais F, Tenca C, Cimino G, et al. CD1d expression on B-precursor acute lymphoblastic leukemia subsets with poor prognosis. Leukemia 2005;19:551–6.

    PubMed  CAS  Google Scholar 

  57. Metelitsa LS, Weinberg KI, Emanuel PD, Seeger RC. Expression of CD1d by myelomonocytic leukemias provides a target for cytotoxic NKT cells. Leukemia 2003;17:1068–77.

    Article  PubMed  CAS  Google Scholar 

  58. Hayakawa Y, Godfrey DI, Smyth MJ. Alpha-galactosylceramide: potential immunomodulatory activity and future application. Curr Med Chem. 2004;11:241–52.

    Article  PubMed  CAS  Google Scholar 

  59. Giaccone G, Punt CJ, Ando Y, et al. A phase I study of the natural killer T-cell ligand alpha-galactosylceramide (KRN7000) in patients with solid tumors. Clin Cancer Res. 2002;8:3702–9.

    PubMed  CAS  Google Scholar 

  60. Toura I, Kawano T, Akutsu Y, Nakayama T, Ochiai T, Taniguchi M. Cutting edge: inhibition of experimental tumor metastasis by dendritic cells pulsed with alpha-galactosylceramide. J Immunol. 1999;163:2387–91.

    PubMed  CAS  Google Scholar 

  61. Shimizu K, Hidaka M, Kadowaki N, et al. Evaluation of the function of human invariant NKT cells from cancer patients using alpha-galactosylceramide-loaded murine dendritic cells. J Immunol. 2006;177:3484–92.

    PubMed  CAS  Google Scholar 

  62. Fontaine P, Roy-Proulx G, Knafo L, Baron C, Roy DC, Perreault C. Adoptive transfer of minor histocompatibility antigen-specific T lymphocytes eradicates leukemia cells without causing graft-versus-host disease. Nat Med. 2001;7:789–94.

    Article  PubMed  CAS  Google Scholar 

  63. 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;96:8639–44.

    Google Scholar 

  64. Akatsuka Y, Nishida T, Kondo E, et al. Identification of a polymorphic gene, BCL2A1, encoding two novel hematopoietic lineage-specific minor histocompatibility antigens. J Exp Med. 2003;197:1489–500.

    Article  PubMed  CAS  Google Scholar 

  65. den Haan JM, Meadows LM, Wang W, et al. The minor histocompatibility antigen HA-1: a diallelic gene with a single amino acid polymorphism. Science 1998;279:1054–7.

    Article  Google Scholar 

  66. Dolstra H, Fredrix H, Maas F, et al. A human minor histocompatibility antigen specific for B cell acute lymphoblastic leukemia. J Exp Med. 1999;189:301–8.

    Article  PubMed  CAS  Google Scholar 

  67. Meadows L, Wang W, den Haan JM, et al. The HLA-A*0201-restricted H-Y antigen contains a posttranslationally modified cysteine that significantly affects T cell recognition. Immunity 1997;6:273–81.

    Article  PubMed  CAS  Google Scholar 

  68. Murata M, Warren EH, Riddell SR. A human minor histocompatibility antigen resulting from differential expression due to a gene deletion. J Exp Med. 2003;197:1279–89.

    Article  PubMed  CAS  Google Scholar 

  69. Kawase T, Nannya Y, Torikai H, et al. Identification of human minor histocompatibility antigens based on genetic association with highly parallel genotyping of pooled DNA. Blood 2008;111:3286–94.

    Article  PubMed  CAS  Google Scholar 

  70. Brickner AG, Evans AM, Mito JK, et al. The PANE1 gene encodes a novel human minor histocompatibility antigen that is selectively expressed in B-lymphoid cells and B-CLL. Blood 2006;107:3779–86.

    Article  PubMed  CAS  Google Scholar 

  71. de Rijke B, van Horssen-Zoetbrood A, Beekman JM, et al. A frameshift polymorphism in P2X5 elicits an allogeneic cytotoxic T lymphocyte response associated with remission of chronic myeloid leukemia. J Clin Invest. 2005;115:3506–16.

    Article  PubMed  CAS  Google Scholar 

  72. Pierce RA, Field ED, Mutis T, et al. The HA-2 minor histocompatibility antigen is derived from a diallelic gene encoding a novel human class I myosin protein. J Immunol. 2001;167:3223–30.

    PubMed  CAS  Google Scholar 

  73. Torikai H, Akatsuka Y, Miyazaki M, et al. A novel HLA-A*3303-restricted minor histocompatibility antigen encoded by an unconventional open reading frame of human TMSB4Y gene. J Immunol. 2004;173:7046–54.

    PubMed  CAS  Google Scholar 

  74. Warren EH, Gavin MA, Simpson E, et al. The human UTY gene encodes a novel HLA-B8-restricted H-Y antigen. J Immunol. 2000;164:2807–14.

    PubMed  CAS  Google Scholar 

  75. Carlson CS, Eberle MA, Rieder MJ, Smith JD, Kruglyak L, Nickerson DA. Additional SNPs and linkage-disequilibrium analyses are necessary for whole-genome association studies in humans. Nat Genet. 2003;33:518–21.

    Article  PubMed  CAS  Google Scholar 

  76. Wang W, Meadows LR, den Haan JM, et al. Human H-Y: a male-specific histocompatibility antigen derived from the SMCY protein. Science 1995;269:1588–90.

    Article  PubMed  CAS  Google Scholar 

  77. Mutis T, Gillespie G, Schrama E, Falkenburg JH, Moss P, Goulmy E. Tetrameric HLA class I-minor histocompatibility antigen peptide complexes demonstrate minor histocompatibility antigen-specific cytotoxic T lymphocytes in patients with graft-versus-host disease. Nat Med. 1999;5:839–42.

    Article  PubMed  CAS  Google Scholar 

  78. Randolph SS, Gooley TA, Warren EH, Appelbaum FR, Riddell SR. Female donors contribute to a selective graft-versus-leukemia effect in male recipients of HLA-matched, related hematopoietic stem cell transplants. Blood 2004;103:347–52.

    Article  PubMed  CAS  Google Scholar 

  79. Ivanov R, Aarts T, Hol S, et al. Identification of a 40S ribosomal protein S4-derived H-Y epitope able to elicit a lymphoblast-specific cytotoxic T lymphocyte response. Clin Cancer Res. 2005;11:1694–703.

    Article  PubMed  CAS  Google Scholar 

  80. Pierce RA, Field ED, den Haan JM, et al. Cutting edge: the HLA-A*0101-restricted HY minor histocompatibility antigen originates from DFFRY and contains a cysteinylated cysteine residue as identified by a novel mass spectrometric technique. J Immunol. 1999;163:6360–4.

    PubMed  CAS  Google Scholar 

  81. Rosinski KV, Fujii N, Mito JK, et al. DDX3Y encodes a class I MHC-restricted H-Y antigen that is expressed in leukemic stem cells. Blood 2008;111:4817–26.

    Article  PubMed  CAS  Google Scholar 

  82. Dickinson AM, Wang XN, Sviland L, et al. In situ dissection of the graft-versus-host activities of cytotoxic T cells specific for minor histocompatibility antigens. Nat Med. 2002;8:410–4.

    Article  PubMed  CAS  Google Scholar 

  83. Warren EH, Vigneron NJ, Gavin MA, et al. An antigen produced by splicing of noncontiguous peptides in the reverse order. Science 2006;313:1444–7.

    Article  PubMed  CAS  Google Scholar 

  84. Marijt WA, Heemskerk MH, Kloosterboer FM, et al. 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. 2003;100:2742–7.

    Google Scholar 

  85. Spierings E, Hendriks M, Absi L, et al. Phenotype frequencies of autosomal minor histocompatibility antigens display significant differences among populations. PLoS Genet. 2007;3:e103.

    Article  PubMed  CAS  Google Scholar 

  86. Bocchia M, Wentworth PA, Southwood S, et al. Specific binding of leukemia oncogene fusion protein peptides to HLA class I molecules. Blood 1995;85:2680–4.

    PubMed  CAS  Google Scholar 

  87. Bocchia M, Korontsvit T, Xu Q, et al. Specific human cellular immunity to bcr-abl oncogene-derived peptides. Blood 1996;87:3587–92.

    PubMed  CAS  Google Scholar 

  88. Buzyn A, Ostankovitch M, Zerbib A, et al. Peptides derived from the whole sequence of BCR-ABL bind to several class I molecules allowing specific induction of human cytotoxic T lymphocytes. Eur J Immunol. 1997;27:2066–72.

    Article  PubMed  CAS  Google Scholar 

  89. Yotnda P, Firat H, Garcia-Pons F, et al. Cytotoxic T cell response against the chimeric p210 BCR-ABL protein in patients with chronic myelogenous leukemia. J Clin Invest. 1998;101:2290–6.

    Article  PubMed  CAS  Google Scholar 

  90. Osman Y, Takahashi M, Zheng Z, et al. 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;13:166–74.

    Article  PubMed  CAS  Google Scholar 

  91. Clark RE, Dodi IA, Hill SC, et al. Direct evidence that leukemic cells present HLA-associated immunogenic peptides derived from the BCR-ABL b3a2 fusion protein. Blood 2001;98:2887–93.

    Article  PubMed  CAS  Google Scholar 

  92. Butt NM, Wang L, Abu-Eisha HM, Christmas SE, Clark RE. BCR-ABL-specific T cells can be detected in healthy donors and in chronic myeloid leukemia patients following allogeneic stem cell transplantation. Blood 2004;103:3245.

    Article  PubMed  CAS  Google Scholar 

  93. Westermann J, Schlimper C, Richter G, Mohm J, Dorken B, Pezzutto A. T cell recognition of bcr/abl in healthy donors and in patients with chronic myeloid leukaemia. Br J Haematol. 2004;125:213–6.

    Article  PubMed  Google Scholar 

  94. Butt NM, Rojas JM, Wang L, Christmas SE, Abu-Eisha HM, Clark RE. Circulating bcr-abl-specific CD8+ T cells in chronic myeloid leukemia patients and healthy subjects. Haematologica 2005;90:1315–23.

    PubMed  CAS  Google Scholar 

  95. Bocchia M, Gentili S, Abruzzese E, et al. Effect of a p210 multipeptide vaccine associated with imatinib or interferon in patients with chronic myeloid leukaemia and persistent residual disease: a multicentre observational trial. Lancet 2005;365:657–62.

    PubMed  CAS  Google Scholar 

  96. Hewitt SM, Hamada S, McDonnell TJ, Rauscher FJ 3rd, Saunders GF. Regulation of the proto-oncogenes bcl-2 and c-myc by the Wilms’ tumor suppressor gene WT1. Cancer Res. 1995;55:5386–9.

    PubMed  CAS  Google Scholar 

  97. Tsuboi A, Oka Y, Ogawa H, et al. Constitutive expression of the Wilms’ tumor gene WT1 inhibits the differentiation of myeloid progenitor cells but promotes their proliferation in response to granulocyte-colony stimulating factor (G-CSF). Leuk Res. 1999;23:499–505.

    Article  PubMed  CAS  Google Scholar 

  98. Bellantuono I, Gao L, Parry S, et al. Two distinct HLA-A0201-presented epitopes of the Wilms tumor antigen 1 can function as targets for leukemia-reactive CTL. Blood 2002;100:3835–7.

    Article  PubMed  CAS  Google Scholar 

  99. Xue SA, Gao L, Hart D, et al. Elimination of human leukemia cells in NOD/SCID mice by WT1-TCR gene-transduced human T cells. Blood 2005;106:3062–7.

    Article  PubMed  CAS  Google Scholar 

  100. Tsuji T, Yasukawa M, Matsuzaki J, et al. Generation of tumor-specific, HLA class I-restricted human Th1 and Tc1 cells by cell engineering with tumor peptide-specific T-cell receptor genes. Blood 2005;106:470–6.

    Article  PubMed  CAS  Google Scholar 

  101. Oka Y, Tsuboi A, Taguchi T, et al. Induction of WT1 (Wilms’ tumor gene)-specific cytotoxic T lymphocytes by WT1 peptide vaccine and the resultant cancer regression. Proc Natl Acad Sci USA. 2004;101:13885–90.

    Google Scholar 

  102. Mailander V, Scheibenbogen C, Thiel E, Letsch A, Blau IW, Keilholz U. Complete remission in a patient with recurrent acute myeloid leukemia induced by vaccination with WT1 peptide in the absence of hematological or renal toxicity. Leukemia 2004;18:165–6.

    Article  PubMed  CAS  Google Scholar 

  103. Keilholz U, Letsch A, Asemissen A, et al. Clinical and immune responses of WT-1 peptide vaccination in patients with acute myeloid leukemia. American Society of Clinical Oncology Annual Meeting Proceedings. J Clin Oncol. 2006;24:2511a.

    Google Scholar 

  104. Rao NV, Rao GV, Marshall BC, Hoidal JR. Biosynthesis and processing of proteinase 3 in U937 cells. Processing pathways are distinct from those of cathepsin G. J Biol Chem. 1996;271:2972–8.

    Article  PubMed  CAS  Google Scholar 

  105. Lindmark A, Gullberg U, Olsson I. Processing and intracellular transport of cathepsin G and neutrophil elastase in the leukemic myeloid cell line U-937-modulation by brefeldin A, ammonium chloride, and monensin. J Leukoc Biol. 1994;55:50–7.

    PubMed  CAS  Google Scholar 

  106. Franssen CF, Stegeman CA, Kallenberg CG, et al. Antiproteinase 3- and antimyeloperoxidase-associated vasculitis. Kidney Int. 2000;57:2195–206.

    Article  PubMed  CAS  Google Scholar 

  107. Borregaard N, Cowland JB. Granules of the human neutrophilic polymorphonuclear leukocyte. Blood 1997;89:3503–21.

    PubMed  CAS  Google Scholar 

  108. Brouwer E, Stegeman CA, Huitema MG, Limburg PC, Kallenberg CG. T cell reactivity to proteinase 3 and myeloperoxidase in patients with Wegener’s granulomatosis (WG). Clin Exp Immunol. 1994;98:448–53.

    Article  PubMed  CAS  Google Scholar 

  109. Dengler R, Munstermann U, al-Batran S, et al. Immunocytochemical and flow cytometric detection of proteinase 3 (myeloblastin) in normal and leukaemic myeloid cells. Br J Haematol. 1995;89:250–7.

    Article  PubMed  CAS  Google Scholar 

  110. Molldrem JJ Lee PP, Wang C, Champlin RE, Davis MM. A PR1-human leukocyte antigen-A2 tetramer can be used to isolate low-frequency cytotoxic T lymphocytes from healthy donors that selectively lyse chronic myelogenous leukemia. Cancer Res. 1999;59:2675–81.

    PubMed  CAS  Google Scholar 

  111. Heslop HE, Stevenson FK, Molldrem JJ. Immunotherapy of hematologic malignancy. Hematology Am Soc Hematol Educ Program. 2003;331–49.

    Google Scholar 

  112. Qazilbash MH, Wieder E, Rios R, Lu S, Kant S, Giralt S, Estey E, Thall P, de Lima M, Couriel D, Champlin RE, Komanduri K, Molldrem JJ. Vaccination with the PR1 leukemia-associated antigen can induce complete remission in patients with myeloid leukemia. Blood 2004;104:259a.

    Google Scholar 

  113. Rezvani K, Yong AS, Mielke S, et al. Leukemia-associated antigen-specific T-cell responses following combined PR1 and WT1 peptide vaccination in patients with myeloid malignancies. Blood 2008;111:236–42.

    Article  PubMed  CAS  Google Scholar 

  114. Entwistle J, Zhang S, Yang B, et al. Characterization of the murine gene encoding the hyaluronan receptor RHAMM. Gene 1995;163:233–8.

    Article  PubMed  CAS  Google Scholar 

  115. Hall CL, Yang B, Yang X, et al. Overexpression of the hyaluronan receptor RHAMM is transforming and is also required for H-ras transformation. Cell 1995;8:19–26.

    Article  Google Scholar 

  116. Greiner J, Li L, Ringhoffer M, et al. Identification and characterization of epitopes of the receptor for hyaluronic acid-mediated motility (RHAMM/CD168) recognized by CD8+ T cells of HLA-A2-positive patients with acute myeloid leukemia. Blood 2005;106:938–45.

    Article  PubMed  CAS  Google Scholar 

  117. Ho VT, Soiffer RJ. The history and future of T-cell depletion as graft-versus-host disease prophylaxis for allogeneic hematopoietic stem cell transplantation. Blood 2001;98:3192–204.

    Article  PubMed  CAS  Google Scholar 

  118. Jakubowski AA, Small TN, Young JW, et al. T cell depleted stem-cell transplantation for adults with hematologic malignancies: sustained engraftment of HLA-matched related donor grafts without the use of antithymocyte globulin. Blood 2007;110:4552–9.

    Article  PubMed  CAS  Google Scholar 

  119. Almyroudis NG, Jakubowski A, Jaffe D, et al. Predictors for persistent cytomegalovirus reactivation after T-cell-depleted allogeneic hematopoietic stem cell transplantation. Transpl Infect Dis. 2007;9:286–94.

    Article  PubMed  CAS  Google Scholar 

  120. Andre-Schmutz I, Le Deist F, Hacein-Bey-Abina S, et al. Immune reconstitution without graft-versus-host disease after haemopoietic stem-cell transplantation: a phase 1/2 study. Lancet 2002;360:130–7.

    Article  PubMed  Google Scholar 

  121. Hartwig UF, Nonn M, Khan S, Meyer RG, Huber C, Herr W. Depletion of alloreactive T cells via CD69: implications on antiviral, antileukemic and immunoregulatory T lymphocytes. Bone Marrow Transplant. 2006;37:297–305.

    Article  PubMed  CAS  Google Scholar 

  122. Wehler TC, Nonn M, Brandt B, et al. Targeting the activation-induced antigen CD137 can selectively deplete alloreactive T cells from antileukemic and antitumor donor T-cell lines. Blood 2007;109:365–73.

    Article  PubMed  CAS  Google Scholar 

  123. Anderson BE, McNiff J, Yan J, et al. Memory CD4+ T cells do not induce graft-versus-host disease. J Clin Invest. 2003;112:101–8.

    PubMed  CAS  Google Scholar 

  124. Chen BJ, Cui X, Sempowski GD, Liu C, Chao NJ. Transfer of allogeneic CD62L-memory T cells without graft-versus-host disease. Blood 2004;103:1534–41.

    Article  PubMed  CAS  Google Scholar 

  125. Xystrakis E, Bernard I, Dejean AS, Alsaati T, Druet P, Saoudi A. Alloreactive CD4 T lymphocytes responsible for acute and chronic graft-versus-host disease are contained within the CD45RChigh but not the CD45RClow subset. Eur J Immunol. 2004;34:408–17.

    Article  PubMed  CAS  Google Scholar 

  126. Zheng H, Matte-Martone C, Li H, et al. Effector memory CD4+ T cells mediate graft-versus-leukemia without inducing graft-versus-host disease. Blood 2008;111:2476–84.

    Article  PubMed  CAS  Google Scholar 

  127. Shlomchik WD. Graft-versus-host disease. Nat Rev Immunol. 2007;7:340–52.

    Article  PubMed  CAS  Google Scholar 

  128. Sallusto F, Geginat J, Lanzavecchia A. Central memory and effector memory T cell subsets: function, generation, and maintenance. Annu Rev Immunol. 2004;22:745–63.

    Article  PubMed  CAS  Google Scholar 

  129. Sallusto F, Langenkamp A, Geginat J, Lanzavecchia A. Functional subsets of memory T cells identified by CCR7 expression. Curr Top Microbiol Immunol. 2000;251:167–71.

    Article  PubMed  CAS  Google Scholar 

  130. Willinger T, Freeman T, Hasegawa H, McMichael AJ, Callan MF. Molecular signatures distinguish human central memory from effector memory CD8 T cell subsets. J Immunol. 2005;175:5895–903.

    PubMed  CAS  Google Scholar 

  131. Arstila TP, Casrouge A, Baron V, Even J, Kanellopoulos J, Kourilsky P. A direct estimate of the human alphabeta T cell receptor diversity. Science 1999;286:958–61.

    Article  PubMed  CAS  Google Scholar 

  132. Bitmansour AD, Waldrop SL, Pitcher CJ, et al. Clonotypic structure of the human CD4+ memory T cell response to cytomegalovirus. J Immunol. 2001;167:1151–63.

    PubMed  CAS  Google Scholar 

  133. Koelle DM, Liu Z, McClurkan CL, et al. Immunodominance among herpes simplex virus-specific CD8 T cells expressing a tissue-specific homing receptor. Proc Natl Acad Sci USA. 2003;100:12899–904.

    Google Scholar 

  134. Manley TJ, Luy L, Jones T, Boeckh M, Mutimer H, Riddell SR. Immune evasion proteins of human cytomegalovirus do not prevent a diverse CD8+ cytotoxic T-cell response in natural infection. Blood 2004;104:1075–82.

    Article  PubMed  CAS  Google Scholar 

  135. Frey CR, Sharp MA, Min AS, Schmid DS, Loparev V, Arvin AM. Identification of CD8+ T cell epitopes in the immediate early 62 protein (IE62) of varicella-zoster virus, and evaluation of frequency of CD8+ T cell response to IE62, by use of IE62 peptides after varicella vaccination. J Infect Dis. 2003;188:40–52.

    Article  PubMed  CAS  Google Scholar 

  136. Hislop AD, Gudgeon NH, Callan MF, et al. EBV-specific CD8+ T cell memory: relationships between epitope specificity, cell phenotype, and immediate effector function. J Immunol. 2001;167:2019–29.

    PubMed  CAS  Google Scholar 

  137. Burrows SR, Silins SL, Khanna R, et al. Cross-reactive memory T cells for Epstein-Barr virus augment the alloresponse to common human leukocyte antigens: degenerate recognition of major histocompatibility complex-bound peptide by T cells and its role in alloreactivity. Eur J Immunol. 1997;27:1726–36.

    Article  PubMed  CAS  Google Scholar 

  138. Elkington R, Khanna R. Cross-recognition of human alloantigen by cytomegalovirus glycoprotein-specific CD4+ cytotoxic T lymphocytes: implications for graft-versus-host disease. Blood 2005;105:1362–4.

    Article  PubMed  CAS  Google Scholar 

  139. Rapoport AP, Stadtmauer EA, Aqui N, et al. Restoration of immunity in lymphopenic individuals with cancer by vaccination and adoptive T-cell transfer. Nat Med. 2005;11:1230–7.

    Article  PubMed  CAS  Google Scholar 

  140. Leen AM, Myers GD, Sili U, et al. Monoculture-derived T lymphocytes specific for multiple viruses expand and produce clinically relevant effects in immunocompromised individuals. Nat Med. 2006;12:1160–6.

    Article  PubMed  CAS  Google Scholar 

  141. Rooney CM, Smith CA, Ng CY, et al. Infusion of cytotoxic T cells for the prevention and treatment of Epstein-Barr virus-induced lymphoma in allogeneic transplant recipients. Blood 1998;92:1549–55.

    PubMed  CAS  Google Scholar 

  142. Walter EA, Greenberg PD, Gilbert MJ, et al. Reconstitution of cellular immunity against cytomegalovirus in recipients of allogeneic bone marrow by transfer of T-cell clones from the donor. N Engl J Med. 1995;333:1038–44.

    Article  PubMed  CAS  Google Scholar 

  143. Dunbar PR, Ogg GS, Chen J, Rust N, van der Bruggen P, Cerundolo V. Direct isolation, phenotyping and cloning of low-frequency antigen-specific cytotoxic T lymphocytes from peripheral blood. Curr Biol. 1998;8:413–6.

    Article  PubMed  CAS  Google Scholar 

  144. Ho WY, Nguyen HN, Wolfl M, Kuball J, Greenberg PD. In vitro methods for generating CD8+ T-cell clones for immunotherapy from the naive repertoire. J Immunol Methods. 2006;310:40–52.

    Article  PubMed  CAS  Google Scholar 

  145. Wolfl M, Kuball J, Ho WY, et al. Activation-induced expression of CD137 permits detection, isolation, and expansion of the full repertoire of CD8+ T cells responding to antigen without requiring knowledge of epitope specificities. Blood 2007;110:201–10.

    Article  PubMed  CAS  Google Scholar 

  146. Yee C, Thompson JA, Byrd D, et al. Adoptive T cell therapy using antigen-specific CD8+ T cell clones for the treatment of patients with metastatic melanoma: in vivo persistence, migration, and antitumor effect of transferred T cells. Proc Natl Acad Sci USA. 2002;99:16168–73.

    Google Scholar 

  147. Dudley ME, Wunderlich JR, Robbins PF, et al. Cancer regression and autoimmunity in patients after clonal repopulation with antitumor lymphocytes. Science 2002;298:850–4.

    Article  PubMed  CAS  Google Scholar 

  148. Gattinoni L, Powell DJ Jr, Rosenberg SA, Restifo NP. Adoptive immunotherapy for cancer: building on success. Nat Rev Immunol. 2006;6:383–93.

    Article  PubMed  CAS  Google Scholar 

  149. Berger C, Jensen MC, Lansdorp PM, Gough M, Elliott C, Riddell SR. Adoptive transfer of effector CD8+ T cells derived from central memory cells establishes persistent T cell memory in primates. J Clin Invest. 2008;118:294–305.

    Article  PubMed  CAS  Google Scholar 

  150. Hinrichs CS, Spolski R, Paulos CM, et al. IL-2 and IL-21 confer opposing differentiation programs to CD8+ T cells for adoptive immunotherapy. Blood 2008;111:5326–33.

    Article  PubMed  CAS  Google Scholar 

  151. Klebanoff CA, Gattinoni L, Torabi-Parizi P, et al. Central memory self/tumor-reactive CD8+ T cells confer superior antitumor immunity compared with effector memory T cells. Proc Natl Acad Sci USA. 2005;102:9571–6.

    Google Scholar 

  152. Clay TM, Custer MC, Sachs J, Hwu P, Rosenberg SA, Nishimura MI. Efficient transfer of a tumor antigen-reactive TCR to human peripheral blood lymphocytes confers anti-tumor reactivity. J Immunol. 1999;163:507–13.

    PubMed  CAS  Google Scholar 

  153. Stanislawski T, Voss RH, Lotz C, et al. Circumventing tolerance to a human MDM2-derived tumor antigen by TCR gene transfer. Nat Immunol. 2001;2:962–70.

    Article  PubMed  CAS  Google Scholar 

  154. Cohen CJ, Zhao Y, Zheng Z, Rosenberg SA, Morgan RA. Enhanced antitumor activity of murine-human hybrid T-cell receptor (TCR) in human lymphocytes is associated with improved pairing and TCR/CD3 stability. Cancer Res. 2006;66:8878–86.

    Article  PubMed  CAS  Google Scholar 

  155. Kuball J, Dossett ML, Wolfl M, et al. Facilitating matched pairing and expression of TCR chains introduced into human T cells. Blood 2007;109:2331–8.

    Article  PubMed  CAS  Google Scholar 

  156. Eshhar Z, Waks T, Gross G, Schindler DG. Specific activation and targeting of cytotoxic lymphocytes through chimeric single chains consisting of antibody-binding domains and the gamma or zeta subunits of the immunoglobulin and T-cell receptors. Proc Natl Acad Sci USA. 1993;90:720–4.

    Google Scholar 

  157. Sadelain M, Riviere I, Brentjens R. Targeting tumours with genetically enhanced T lymphocytes. Nat Rev Cancer. 2003;3:35–45.

    Article  PubMed  CAS  Google Scholar 

  158. Stephan MT, Ponomarev V, Brentjens RJ, et al. T cell-encoded CD80 and 4-1BBL induce auto- and transcostimulation, resulting in potent tumor rejection. Nat Med. 2007;13:1440–9.

    Article  PubMed  CAS  Google Scholar 

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Molldrem, J., Riddell, S. (2009). Understanding and Enhancing the Graft-Versus-Leukemia Effect After Hematopoietic Stem Cell Transplantation. In: Bishop, M. (eds) Hematopoietic Stem Cell Transplantation. Cancer Treatment and Research, vol 144. Springer, Boston, MA. https://doi.org/10.1007/978-0-387-78580-6_8

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