Seminars in Hematology
Volume 46, Issue 1 , Pages 89-99 , January 2009

Immunotherapy in Acute Leukemia

  • Wing Leung

      Affiliations

    • Corresponding Author InformationAddress correspondence to Wing Leung, MD, PhD, Department of Oncology, Mail Stop 260, St. Jude Children's Research Hospital, 262, Danny Thomas Place, Memphis, TN 38105

References 

  1. Waldmann TA. Immunotherapy: past, present and future. Nat Med. 2003;9:269–277
  2. Kao JH, Chen DS. Recent updates in hepatitis vaccination and the prevention of hepatocellular carcinoma. Int J Cancer. 2002;97:269–271
  3. D'Souza G, Kreimer AR, Viscidi R, Pawlita M, Fakhry C, Koch WM, et al. Case-control study of human papillomavirus and oropharyngeal cancer. N Engl J Med. 2007;356:1944–1956
  4. Future II Study Group. Quadrivalent vaccine against human papillomavirus to prevent high-grade cervical lesions. N Engl J Med. 2007;356:1915–1927
  5. Coley WB. The treatment of malignant tumors by repeated inoculations of erysipelas (With a report of ten original cases in American Journal of Medical Science, 1893). Clin Orthop Relat Res. 1991;262:3–11
  6. Starnes CO. Coley's toxins in perspective. Nature. 1992;357:11–12
  7. Kohler G, Milstein C. Continuous cultures of fused cells secreting antibody of predefined specificity. Nature. 1975;256:495–497
  8. Miller RA, Maloney DG, Warnke R, Levy R. Treatment of B-cell lymphoma with monoclonal anti-idiotype antibody. N Engl J Med. 1982;306:517–522
  9. Aggarwal S. What's fueling the biotech engine?. Nat Biotechnol. 2007;25:1097–1104
  10. Burnet FM. The concept of immunological surveillance. Prog Exp Tumor Res. 1970;13:1–27
  11. Kaplan DH, Shankaran V, Dighe AS, Stockert E, Aguet M, Old LJ, et al. Demonstration of an interferon gamma-dependent tumor surveillance system in immunocompetent mice. Proc Natl Acad Sci U S A. 1998;95:7556–7561
  12. Shankaran V, Ikeda H, Bruce AT, White JM, Swanson PE, Old LJ, et al. IFNgamma and lymphocytes prevent primary tumour development and shape tumour immunogenicity. Nature. 2001;410:1107–1111
  13. Dunn GP, Bruce AT, Ikeda H, Old LJ, Schreiber RD. Cancer immunoediting: from immunosurveillance to tumor escape. Nat Immunol. 2002;3:991–998
  14. Labbe A, Tran AH, Paige CJ. Murine model of immune-mediated rejection of the acute lymphoblastic leukemia 70Z/3. J Immunol. 2006;176:5354–5361
  15. Swann JB, Smyth MJ. Immune surveillance of tumors. J Clin Invest. 2007;117:1137–1146
  16. Koebel CM, Vermi W, Swann JB, Zerafa N, Rodig SJ, Old LJ, et al. Adaptive immunity maintains occult cancer in an equilibrium state. Nature. 2007;450:903–907
  17. Grulich AE, van Leeuwen MT, Falster MO, Vajdic CM. Incidence of cancers in people with HIV/AIDS compared with immunosuppressed transplant recipients: a meta-analysis. Lancet. 2007;370:59–67
  18. Finn OJ. Cancer immunology. N Engl J Med. 2008;358:2704–2715
  19. Roithmaier S, Haydon AM, Loi S, Esmore D, Griffiths A, Bergin P, et al. Incidence of malignancies in heart and/or lung transplant recipients: a single-institution experience. J Heart Lung Transplant. 2007;26:845–849
  20. Galon J, Costes A, Sanchez-Cabo F, et al. Type, density, and location of immune cells within human colorectal tumors predict clinical outcome. Science. 2006;313:1960–1964
  21. Sato E, Olson SH, Ahn J, Bundy B, Nishikawa H, Qian F, et al. Intraepithelial CD8+ tumor-infiltrating lymphocytes and a high CD8+/regulatory T cell ratio are associated with favorable prognosis in ovarian cancer. Proc Natl Acad Sci U S A. 2005;102:18538–18543
  22. Piersma SJ, Jordanova ES, van Poelgeest MI, Kwappenberg KM, van der Hulst JM, Drijfhout JW, et al. High number of intraepithelial CD8+ tumor-infiltrating lymphocytes is associated with the absence of lymph node metastases in patients with large early-stage cervical cancer. Cancer Res. 2007;67:354–361
  23. Naito Y, Saito K, Shiiba K, Ohuchi A, Saigenji K, Nagura H, et al. CD8+ T cells infiltrated within cancer cell nests as a prognostic factor in human colorectal cancer. Cancer Res. 1998;58:3491–3494
  24. Schumacher K, Haensch W, Roefzaad C, Schlag PM. Prognostic significance of activated CD8(+) T cell infiltrations within esophageal carcinomas. Cancer Res. 2001;61:3932–3936
  25. Wakabayashi O, Yamazaki K, Oizumi S, Hommura F, Kinoshita I, Ogura S, et al. CD4+ T cells in cancer stroma, not CD8+ T cells in cancer cell nests, are associated with favorable prognosis in human non-small cell lung cancers. Cancer Sci. 2003;94:1003–1009
  26. Kohrt HE, Nouri N, Nowels K, Johnson D, Holmes S, Lee PP, et al. Profile of immune cells in axillary lymph nodes predicts disease-free survival in breast cancer. PLoS Med. 2005;2:e284
  27. Sharma P, Shen Y, Wen S, Yamada S, Jungbluth AA, Gnjatic S, et al. CD8 tumor-infiltrating lymphocytes are predictive of survival in muscle-invasive urothelial carcinoma. Proc Natl Acad Sci U S A. 2007;104:3967–3972
  28. Dave SS, Wright G, Tan B, Rosenwald A, Gascoyne RD, Chan WC, et al. Prediction of survival in follicular lymphoma based on molecular features of tumor-infiltrating immune cells. N Engl J Med. 2004;351:2159–2169
  29. Imai K, Matsuyama S, Miyake S, Suga K, Nakachi K. Natural cytotoxic activity of peripheral-blood lymphocytes and cancer incidence: an 11-year follow-up study of a general population. Lancet. 2000;356:1795–1799
  30. Mahoney DH, Starling KA. Immunotherapy in acute leukemias (Possible applications in children). Am J Pediatr Hematol Oncol. 1981;3:410–418
  31. Gojo I. Improving treatment strategies for acute lymphoblastic leukemia by combining immunotherapy and chemotherapy. Leuk Res. 2008;32:847–849
  32. Finke LH, Wentworth K, Blumenstein B, Rudolph NS, Levitsky H, Hoos A. Lessons from randomized phase III studies with active cancer immunotherapies—outcomes from the 2006 meeting of the Cancer Vaccine Consortium (CVC). Vaccine. 2007;25(2):B97–B109
  33. Blattman JN, Greenberg PD. Cancer immunotherapy: a treatment for the masses. Science. 2004;305:200–205
  34. Smyth MJ, Takeda K, Hayakawa Y, Peschon JJ, van den Brink MR, Yagita H. Nature's TRAIL—on a path to cancer immunotherapy. Immunity. 2003;18:1–6
  35. Krammer PH. CD95's deadly mission in the immune system. Nature. 2007;407:789–795
  36. Khong HT, Restifo NP. Natural selection of tumor variants in the generation of “tumor escape” phenotypes. Nat. Immunol. 2002;3:999–1005
  37. Rosenberg SA, Yang JC, Restifo NP. Cancer immunotherapy: moving beyond current vaccines. Nat Med. 2004;10:909–915
  38. Laheru DA, Pardoll DM, Jaffee EM. Genes to vaccines for immunotherapy: how the molecular biology revolution has influenced cancer immunology. Mol Cancer Ther. 2005;4:1645–1652
  39. Zitvogel L, Tesniere A, Kroemer G. Cancer despite immunosurveillance: immunoselection and immunosubversion. Nat Rev Immunol. 2006;6:715–727
  40. Gabrilovich D. Mechanisms and functional significance of tumour-induced dendritic-cell defects. Nat Rev Immunol. 2004;4:941–952
  41. Cardoso AA, Schultze JL, Boussiotis VA, Freeman GJ, Seamon MJ, Laszlo S, et al. Pre-B acute lymphoblastic leukemia cells may induce T-cell anergy to alloantigen. Blood. 1996;88:41–48
  42. D'Amico G, Vulcano M, Bugarin C, Bianchi G, Pirovano G, Bonamino M, et al. CD40 activation of BCP-ALL cells generates IL-10-producing, IL-12-defective APCs that induce allogeneic T-cell anergy. Blood. 2004;104:744–751
  43. Sica A, Bronte V. Altered macrophage differentiation and immune dysfunction in tumor development. J Clin Invest. 2007;117:1155–1166
  44. Korman AJ, Peggs KS, Allison JP. Checkpoint blockade in cancer immunotherapy. Adv Immunol. 2006;90:297–339
  45. Zou W. Regulatory T cells, tumour immunity and immunotherapy. Nat Rev Immunol. 2006;6:295–307
  46. Yang ZZ, Novak AJ, Stenson MJ, Witzig TE, Ansell SM. Intratumoral CD4+CD25+ regulatory T-cell-mediated suppression of infiltrating CD4+ T cells in B-cell non-Hodgkin lymphoma. Blood. 2006;107:3639–3646
  47. Liu VC, Wong LY, Jang T, Shah AH, Park I, Yang X, et al. Tumor evasion of the immune system by converting CD4+CD25- T cells into CD4+CD25+ T regulatory cells: role of tumor-derived TGF-beta. J Immunol. 2007;178:2883–2892
  48. Terabe M, Matsui S, Noben-Trauth N, Chen H, Watson C, Donaldson DD, et al. NKT cell-mediated repression of tumor immunosurveillance by IL-13 and the IL-4R-STAT6 pathway. Nat Immunol. 2000;1:515–520
  49. Kortylewski M, Kujawski M, Wang T, Wei S, Zhang S, Pilon-Thomas S, et al. Inhibiting Stat3 signaling in the hematopoietic system elicits multicomponent antitumor immunity. Nat Med. 2005;11:1314–1321
  50. Kusmartsev S, Gabrilovich DI. STAT1 signaling regulates tumor-associated macrophage-mediated T cell deletion. J Immunol. 2005;174:4880–4891
  51. Gallina G, Dolcetti L, Serafini P, De Santo C, Marigo I, Colombo MP, et al. Tumors induce a subset of inflammatory monocytes with immunosuppressive activity on CD8+ T cells. J Clin Invest. 2006;116:2777–2790
  52. He X, Stuart JM. Prostaglandin E2 selectively inhibits human CD4+ T cells secreting low amounts of both IL-2 and IL-4. J Immunol. 1999;163:6173–6179
  53. Yang L, DeBusk LM, Fukuda K, Fingleton B, Green-Jarvis B, Shyr Y, et al. Expansion of myeloid immune suppressor Gr+CD11b+ cells in tumor-bearing host directly promotes tumor angiogenesis. Cancer Cell. 2004;6:409–421
  54. Schmielau J, Finn OJ. Activated granulocytes and granulocyte-derived hydrogen peroxide are the underlying mechanism of suppression of t-cell function in advanced cancer patients. Cancer Res. 2001;61:4756–4760
  55. Nagaraj S, Gabrilovich DI. Myeloid-derived suppressor cells. Adv Exp Med Biol. 2007;601:213–223
  56. Kusmartsev S, Nagaraj S, Gabrilovich DI. Tumor-associated CD8+ T cell tolerance induced by bone marrow-derived immature myeloid cells. J Immunol. 2005;175:4583–4592
  57. Sinha P, Clements VK, Bunt SK, Albelda SM, Ostrand-Rosenberg S. Cross-talk between myeloid-derived suppressor cells and macrophages subverts tumor immunity toward a type 2 response. J Immunol. 2007;179:977–983
  58. Johnson BF, Clay TM, Hobeika AC, Lyerly HK, Morse MA. Vascular endothelial growth factor and immunosuppression in cancer: current knowledge and potential for new therapy. Expert Opin Biol Ther. 2007;7:449–460
  59. Uyttenhove C, Pilotte L, Théate I, Stroobant V, Colau D, Parmentier N, et al. Evidence for a tumoral immune resistance mechanism based on tryptophan degradation by indoleamine 2,3-dioxygenase. Nat Med. 2003;9:1269–1274
  60. Munn DH, Mellor AL. Indoleamine 2,3-dioxygenase and tumor-induced tolerance. J Clin Invest. 2007;117:1147–1154
  61. Groh V, Wu J, Yee C, Spies T. Tumour-derived soluble MIC ligands impair expression of NKG2D and T-cell activation. Nature. 2002;419:734–738
  62. Kaiser BK, Yim D, Chow IT, Gonzalez S, Dai Z, Mann HH, et al. Disulphide-isomerase-enabled shedding of tumour-associated NKG2D ligands. Nature. 2007;447:482–486
  63. Medema JP, de Jong J, Peltenburg LT, Verdegaal EM, Gorter A, Bres SA, et al. Blockade of the granzyme B/perforin pathway through overexpression of the serine protease inhibitor PI-9/SPI-6 constitutes a mechanism for immune escape by tumors. Proc Natl Acad Sci U S A. 2001;98:11515–11520
  64. Gilboa E. The makings of a tumor rejection antigen. Immunity. 1999;11:263–270
  65. Bocchia M, Korontsvit T, Xu Q, Mackinnon S, Yang SY, Sette A, et al. Specific human cellular immunity to bcr-abl oncogene-derived peptides. Blood. 1996;87:3587–3592
  66. Bosch GJ, Joosten AM, Kessler JH, Melief CJ, Leeksma OC. Recognition of BCR-ABL positive leukemic blasts by human CD4+ T cells elicited by primary in vitro immunization with a BCR-ABL breakpoint peptide. Blood. 1996;88:3522–3527
  67. Gambacorti-Passerini C, Grignani F, Arienti F, Pandolfi PP, Pelicci PG, Parmiani G. Human CD4 lymphocytes specifically recognize a peptide representing the fusion region of the hybrid protein PML-RAR alpha present in acute promyelocytic leukemia cells. Blood. 1993;81:1369–1375
  68. Yotnda P, Garcia F, Peuchmaur M, Grandchamp B, Duval M, Lemonnier F, et al. Cytotoxic T cell response against the chimeric ETV6-AML1 protein in childhood acute lymphoblastic leukemia. J Clin Invest. 1998;102:455–462
  69. Maia S, Haining WN, Ansén S, Xia Z, Armstrong SA, Seth NP, et al. Gene expression profiling identifies BAX-delta as a novel tumor antigen in acute lymphoblastic leukemia. Cancer Res. 2005;65:10050–10058
  70. Dohnal AM, Inthal A, Felzmann T, Glatt S, Sommergruber W, Mann G, et al. Leukemia-associated antigenic isoforms induce a specific immune response in children with T-ALL. Int J Cancer. 2006;119:2870–2877
  71. Kessler JH, Bres-Vloemans SA, van Veelen PA, de Ru A, Huijbers IJ, Camps M, et al. BCR-ABL fusion regions as a source of multiple leukemia-specific CD8+ T-cell epitopes. Leukemia. 2006;20:1738–1750
  72. Rezvani K, Brenchley JM, Price DA, Kilical Y, Gostick E, Sewell AK, et al. T-cell responses directed against multiple HLA-A*0201-restricted epitopes derived from Wilms' tumor 1 protein in patients with leukemia and healthy donors: identification, quantification, and characterization. Clin Cancer Res. 2005;11:8799–8807
  73. Xiaoling G, Ying L, Jing L, Huifang L, Xia Z, Qingqing F, et al. Induction of anti B-cell malignance CTL response by subfamily-shared peptides derived from variable domain of immunoglobulin heavy chain. Cancer Immunol Immunother. 2005;54:1106–1114
  74. Shabani M, Omran HA, Jeddi-Tehrani M, Vossough P, Faranoush M, Sharifian RA, et al. Overexpression of orphan receptor tyrosine kinase Ror1 as a putative tumor-associated antigen in Iranian patients with acute lymphoblastic leukemia. Tumour Biol. 2007;28:318–326
  75. Van Driessche A, Gao L, Stauss HJ, Ponsaerts P, Van Bockstaele DR, Berneman ZN, et al. Antigen-specific cellular immunotherapy of leukemia. Leukemia. 2005;19:1863–1871
  76. Maggio R, Peragine N, Calabrese E, De Propris MS, Intoppa S, Della Starza I, et al. Generation of functional dendritic cells (DC) in adult acute lymphoblastic leukemia: rationale for a DC-based vaccination program for patients in complete hematological remission. Leuk Lymphoma. 2007;48:302–310
  77. Dilloo D, Brown M, Roskrow M, Zhong W, Holladay M, Holden W, et al. CD40 ligand induces an antileukemia immune response in vivo. Blood. 1997;90:1927–1933
  78. Pospísilová D, Borovicková J, Rozková D, Stary J, Seifertová D, Tobiásová Z, et al. Methods of dendritic cell preparation for acute lymphoblastic leukemia immunotherapy in children. Med Oncol. 2005;22:79–88
  79. Stripecke R, Skelton DC, Gruber T, Afar D, Pattengale PK, Witte ON, et al. 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
  80. Stripecke R, Skelton DC, Pattengale PK, Shimada H, Kohn DB. Combination of CD80 and granulocytẽmacrophage 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
  81. Brentjens RJ, Santos E, Nikhamin Y, Yeh R, Matsushita M, La Perle K, et al. Genetically targeted T cells eradicate systemic acute lymphoblastic leukemia xenografts. Clin Cancer Res. 2007;13:5426–5435
  82. Stripecke R, Cardoso AA, Pepper KA, Skelton DC, Yu XJ, Mascarenhas L, et al. Lentiviral vectors for efficient delivery of CD80 and granulocytẽ-macrophage colony-stimulating factor in human acute lymphoblastic leukemia and acute myeloid leukemia cells to induce antileukemic immune responses. Blood. 2000;96:1317–1326
  83. Cheuk AT, Chan L, Czepulkowski B, Berger SA, Yagita H, Okumura K, et al. Development of a whole cell vaccine for acute myeloid leukaemia. Cancer Immunol Immunother. 2006;55:68–75
  84. Biagi E, Dotti G, Yvon E, Lee E, Pule M, Vigouroux S, et al. Molecular transfer of CD40 and OX40 ligands to leukemic human B cells induces expansion of autologous tumor-reactive cytotoxic T lymphocytes. Blood. 2005;105:2436–2442
  85. Cignetti A, Bryant E, Allione B, Vitale A, Foa R, Cheever MA. CD34(+) acute myeloid and lymphoid leukemic blasts can be induced to differentiate into dendritic cells. Blood. 1999;94:2048–2055
  86. Choudhury BA, Liang JC, Thomas EK, Flores-Romo L, Xie QS, Agusala K, et al. Dendritic cells derived in vitro from acute myelogenous leukemia cells stimulate autologous, antileukemic T-cell responses. Blood. 1999;93:780–786
  87. Cignetti A, Vallario A, Roato I, Circosta P, Allione B, Casorzo L, et al. Leukemia-derived immature dendritic cells differentiate into functionally competent mature dendritic cells that effeciently stimulate T cell responses. J Immunol. 2004;173:2855–2865
  88. Lee J, Sait SN, Wetzler M. Characterization of dendritic-like cells derived from t(9;22) acute lymphoblastic leukemia blasts. Int Immunol. 2004;16:1377–1389
  89. Li L, Giannopoulos K, Reinhardt P, Tabarkiewicz J, Schmitt A, Greiner J, et al. Immunotherapy for patients with acute myeloid leukemia using autologous dendritic cells generated from leukemic blasts. Int J Oncol. 2006;28:855–861
  90. Mohty M, Isnardon D, Charbonnier A, Lafage-Pochitaloff M, Merlin M, Sainty D, et al. Generation of potent Th1 responses from patients with lymphoid malignancies after differentiation of B lymphocytes into dendritic-like cells. Int Immunol. 2002;14:741–750
  91. Todisco E, Gaipa G, Biagi E, Bonamino M, Gramigna R, Introna M, et al. CD40 ligand-stimulated B cell precursor leukemic cells elicit interferon-gamma production by autologous bone marrow T cells in childhood acute lymphoblastic leukemia. Leukemia. 2002;16:2046–2054
  92. Rousseau RF, Biagi E, Dutour A, Yvon ES, Brown MP, Lin T, et al. Immunotherapy of high-risk acute leukemia with a recipient (autologous) vaccine expressing transgenic human CD40L and IL-2 after chemotherapy and allogeneic stem cell transplantation. Blood. 2006;107:1332–1341
  93. Borrello IM, Levitsky HI, Stock W, Scher D, Damon LE, Linker CA, et al. Posttransplant immunotherapy with a GMCSF-based tumor vaccine (GVAX) following autologous stem cell transplant (ASCT) for acute myeloid leukemia (AML) [abstract]. Blood. 2003;102:1791a
  94. Qazilbash MH, Wieder E, Rios R, Lu S, Kant S, Giralt S, et al. Vaccination with the PRl leukemia-associated antigen can induce complete remission in patients with myeloid leukemia [abstract]. Blood. 2004;104:259a
  95. Bocchia M, Gentili S, Abruzzese E, Fanelli A, Iuliano F, Tabilio A, 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;365:657–662
  96. Oka Y, Tsuboi A, Taguchi T, Osaki T, Kyo T, Nakajima H, et al. Induction of WTl (Wilms' tumor gene)-specific cytotoxic T lymphocytes by WTl peptide vaccine and the resultant cancer regression. Proc Natl Acad Sci U S A. 2004;101:13885–13890
  97. Redfern CH, Guthrie TH, Bessudo A, Densmore JJ, Holman PR, Janakiraman N, et al. Phase II trial of idiotype vaccination in previously treated patients with indolent non-Hodgkin's lymphoma resulting in durable clinical responses. J Clin Oncol. 2006;24:3107–3112
  98. Inogès S, Rodrìguez-Calvillo M, Zabalegui N, Lòpez-Dìaz de Cerio A, Villanueva H, Soria E, et al. Clinical benefit associated with idiotypic vaccination in patients with follicular lymphoma. J Natl Cancer Inst. 2006;98:1292–1301
  99. Roddie H, Klammer M, Thomas C, Thomson R, Atkinson A, Sproul A, et al. Phase I/II study of vaccination with dendritic-like leukemia cells for the immunotherapy of acute myeloid leukemia. Br J Haematol. 2006;133:152–157
  100. Nowak AK, Lake RA, Marzo AL, Scott B, Heath WR, Collins EJ, et al. Induction of tumor cell apoptosis in vivo increases tumor antigen cross-presentation, cross-priming rather than cross-tolerizing host tumor-specific CD8 T cells. J Immunol. 2003;170:4905–4913
  101. Lutsiak ME, Semnani RT, De Pascalis R, Kashmiri SV, Schlom J, Sabzevari H. Inhibition of CD4(+)25+ T regulatory cell function implicated in enhanced immune response by low-dose cyclophosphamide. Blood. 2005;105:2862–2868
  102. June CH. Adoptive T cell therapy for cancer in the clinic. J Clin Invest. 2007;117:1466–1476
  103. Walter EA, Greenberg PD, Gilbert MJ, Finch RJ, Watanabe KS, Thomas ED, 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;333:1038–1044
  104. Heslop HE, Ng CY, Li C, Smith CA, Loftin SK, Krance RA, et al. Long-term restoration of immunity against Epstein-Barr virus infection by adoptive transfer of gene-modified virus-specific T lymphocytes. Nat Med. 1996;2:551–555
  105. Rooney CM, Smith CA, Ng CY, Loftin SK, Sixbey JW, Gan Y, et al. Infusion of cytotoxic T cells for the prevention and treatment of Epstein-Barr virus-induced lymphoma in allogeneic transplant recipient. Blood. 1998;92:1549–1555
  106. Brodie SJ, Lewinsohn DA, Patternson BK, Jiyamapa D, Krieger J, Corey L, et al. In vivo migration and function of transferred HIV-1-specific cytotoxic T cells. Nat Med. 1999;5:34–41
  107. Rapoport AP, Stadtmauer EA, Aqui N, Badros A, Cotte J, Chrisley L, et al. Restoration of immunity in lymphopenic individuals with cancer by vaccination and adoptive T-cell transfer. Nat Med. 2005;11:1230–1237
  108. Curti BD, Ochoa AC, Powers GC, Kopp WC, Alvord WG, Janik JE, et al. Phase I trial of anti-CD3-stimulated CD4+ T cells, infusional interleukin-2, and cyclophosphamide in patients with advanced cancer. J Clin Oncol. 1998;16:2752–2760
  109. Roskrow MA, Suzuki N, Gan YJ, Sixbey JW, Ng CY, Kimbrough S, et al. Epsteiñ-Barr (EBV)-specific cytotoxic T lymphocytes for the treatment of patients with EBV-positive relapsed Hodgkin's disease. Blood. 1998;91:2925–2934
  110. Schultze JL, Anderson KC, Gilleece MH, Gribben JG, Nadler LM. A pilot study of combined immunotherapy with autologous adoptive tumour-specific T-cell transfer, vaccination with CD40-activated malignant B cells and interleukin 2. Br J Haematol. 2001;113:455–460
  111. Morgan RA, Dudley ME, Wunderlich JR, Hughes MS, Yang JC, Sherry RM, et al. Cancer regression in patients after transfer of genetically engineered lymphocytes. Science. 2006;314:126–129
  112. Jensen MC, Popplewell L, DiGiusto DL, Kalos M, Cooper LJN, Raubitschek A, et al. A first-in-human clinical trial of adoptive therapy using CD19-specific chimeric antigen receptor re-directed T cells for recurrent/refractory follicular lymphoma. Mol Ther. 2007;15:S142
  113. Cardoso AA, Seamon MJ, Afonso HM, Ghia P, Boussiotis VA, Freeman GJ, et al. Ex vivo generation of human anti-pre-B leukemia specific autologous cytolytic T cells. Blood. 1997;90:549–561
  114. Cardoso AA, Veiga JP, Ghia P, Afonso HM, Haining WN, Sallan SE, et al. Adoptive T-cell therapy for B-cell acute lymphoblastic leukemia: preclinical studies. Blood. 1999;94:3531–3540
  115. D'Amico G, Bonamino M, Dander E, Marin V, Basso G, Balduzzi A, et al. T cells stimulated by CD40L positive leukemic blasts-pulsed dendritic cells meet optimal functional requirements for adoptive T-cell therapy. Leukemia. 2006;20:2015–2024
  116. Barbui AM, Borleri G, Conti E, Ciocca A, Salvi A, Micò C, et al. Clinical grade expansion of CD45RA, CD45RO, and CD62L-positive T-cell lines from HLA-compatible donors: high cytotoxic potential against AML and ALL cells. Exp Hematol. 2006;34:475–485
  117. Rössig C, Pscherer S, Landmeier S, Altvater B, Jürgens H, Vormoor J. Adoptive cellular immunotherapy with CD19-specific T cells. Klin Padiatr. 2005;217:351–356
  118. Serrano LM, Pfeiffer T, Olivares S, Numbenjapon T, Bennitt J, Kim D, et al. Differentiation of naive cord-blood T cells into CD19-specific cytolytic effectors for posttransplantation adoptive immunotherapy. Blood. 2006;107:2643–2652
  119. Numbenjapon T, Serrano LM, Singh H, Kowolik CM, Olivares S, Gonzalez N, et al. Characterization of an artificial antigen-presenting cell to propagate cytolytic CD19-specific T cells. Leukemia. 2006;20:1889–1892
  120. Savoldo B, Rooney CM, Di Stasi A, Abken H, Hombach A, Foster AE, et al. Epstein Barr virus-specific cytotoxic T lymphocytes expressing the anti-CD30{zeta} artificial chimeric T-cell receptor for immunotherapy of Hodgkin's disease. Blood. 2007;110:2620–2630
  121. Stauss HJ, Thomas S, Cesco-Gaspere M, Hart DP, Xue SA, Holler A, et al. WT1-specific T cell receptor gene therapy: improving TCR function in transduced T cells. Blood Cells Mol Dis. 2008;40:113–116
  122. Spaapen R, van den Oudenalder K, Ivanov R, Bloem A, Lokhorst H, Mutis T, et al. Rebuilding human leukocyte antigen class II-restricted minor histocompatibility antigen specificity in recall antigen-specific T cells by adoptive T cell receptor transfer: implications for adoptive immunotherapy. Clin Cancer Res. 2007;13:4009–4015
  123. Heemskerk MH, Hagedoorn RS, van der Hoorn MA, van der Veken LT, Hoogeboom M, Kester MG, et al. Efficiency of T-cell receptor expression in dual-specific T cells is controlled by the intrinsic qualities of the TCR chains within the TCR-CD3 complex. Blood. 2007;109:235–243
  124. Kowolik CM, Topp MS, Gonzalez S, Pfeiffer T, Olivares S, Gonzalez N, et al. CD28 costimulation provided through a CD19-specific chimeric antigen receptor enhances in vivo persistence and antitumor efficacy of adoptively transferred T cells. Cancer Res. 2006;66:10995–11004
  125. Pule MA, Straathof KC, Dotti G, Heslop HE, Rooney CM, Brenner MK. A chimeric T cell antigen receptor that augments cytokine release and supports clonal expansion of primary human T cells. Mol Ther. 2005;12:933–941
  126. Maher J, Brentjens RJ, Gunset G, Riviere I, Sadelain M. Human T-lymphocyte cytotoxicity and proliferation directed by a single chimeric TCR/CD28 receptor. Nat Biotechnol. 2002;20:70–75
  127. Wang J, Jensen M, Lin Y, Sui X, Chen E, Lindgren CG, et al. Optimizing adoptive polyclonal T cell immunotherapy of lymphomas, using a chimeric T cell receptor possessing CD28 and CD137 costimulatory domains. Hum Gene Ther. 2007;18:712–725
  128. Finney HM, Akbar AN, Lawson AD. Activation of resting human primary T cells with chimeric receptors: costimulation from CD28, inducible costimulator, CD134, and CD137 in series with signals from the TCR chain. J Immunol. 2004;172:104–113
  129. Quintarelli C, Vera JF, Savoldo B, Giordano Attianese GM, Pule M, Foster A, et al. Co-expression of cytokine and suicide genes to enhance the activity and safety of tumor specific cytotoxic T lymphocytes. Blood. 2007;110:2793–2802
  130. Hsu C, Hughes MS, Zheng Z, Bray RB, Rosenberg SA, Morgan RA. Primary human T lymphocytes engineered with a codon-optimized IL-15 gene resist cytokine withdrawal-induced apoptosis and persist long-term in the absence of exogenous cytokine. J Immunol. 2005;175:7226–7234
  131. Hsu C, Jones SA, Cohen CJ, Zheng Z, Kerstann K, Zhou J, et al. Cytokine-independent growth and clonal expansion of a primary human CD8+ T-cell clone following retroviral transduction with the IL-15 gene. Blood. 2007;109:5168–5177
  132. Rossig C, Bollard CM, Nuchtern JG, Rooney CM, Brenner MK. Epstein-Barr virus-specific human T lymphocytes expressing antitumor chimeric T-cell receptors: potential for improved immunotherapy. Blood. 2002;99:2009–2016
  133. Kershaw MH, Westwood JA, Hwu P. Dual-specific T cells combine proliferation and antitumor activity. Nat Biotechnol. 2002;20:1221–1227
  134. Gough M, Crittenden M, Thanarajasingam U, Sanchez-Perez L, Thompson J, Jevremovie D, et al. Gene therapy to manipulate effector T cell trafficking to tumors for immunotherapy. J Immunol. 2005;174:5766–5773
  135. Bollard CM, Rossig C, Calonge MJ, Huls MH, Wagner HJ, Massague J, et al. Adapting a transforming growth factor-related tumor protection strategy to enhance antitumor immunity. Blood. 2002;99:3179–3187
  136. Lacuesta K, Buza E, Hauser H, Granville L, Pule M, Corboy G, et al. Assessing the safety of cytotoxic T lymphocytes transduced with a dominant negative transforming growth factor-receptor. J Immunother. 2006;29:250–260
  137. Dotti G, Savoldo B, Pule M, Straathof KC, Biagi E, Yvon E, et al. Human cytotoxic T lymphocytes with reduced sensitivity to Fas-induced apoptosis. Blood. 2005;105:4677–4684
  138. Sato T, Neschadim A, Konrad M, Fowler DH, Lavie A, Medin JA. Engineered human tmpk/AZT as a novel enzyme/prodrug axis for suicide gene therapy. Mol Ther. 2007;15:962–970
  139. Berger C, Blau CA, Huang ML, Iuliucci JD, Dalgarno DC, Gaschet J, et al. Pharmacologically regulated Fas-mediated death of adoptively transferred T cells in a nonhuman primate model. Blood. 2004;103:1261–1269
  140. Straathof KC, Pule MAq, Yotnda P, Dotti G, Vanin EF, Brenner MK, et al. An inducible caspase 9 safety switch for T-cell therapy. Blood. 2005;105:4247–4254
  141. Sangiolo D, Lesnikova M, Nash RA, Jensen MC, Nikitine A, Kiem HP, et al. Lentiviral vector conferring resistance to mycophenolate mofetil and sensitivity to ganciclovir for in vivo T-cell selection. Gene Ther. 2007;14:1549–1554
  142. O'Brien TA, Tuong DT, Basso LM, McIvor RS, Orchard PJ. Coexpression of the uracil phosphoribosyltransferase gene with a chimeric human nerve growth factor receptor/cytosine deaminase fusion gene, using a single retroviral vector, augments cytotoxicity of transduced human T cells exposed to 5-fluorocytosine. Hum Gene Ther. 2006;17:518–530
  143. Orchard PJ, Blazar BR, Burger S, Levine B, Basso L, Nelson DM, et al. Clinical-scale selection of anti-CD3/CD28-activated T cells after transduction with a retroviral vector expressing herpes simplex virus thymidine kinase and truncated nerve growth factor receptor. Hum Gene Ther. 2002;13:979–988
  144. 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;13:913–924
  145. Traversari C, Marktel S, Magnani Z, Mangia P, Russo V, Ciceri F, et al. The potential immunogenicity of the TK suicide gene does not prevent full clinical benefit associated with the use of TK-transduced donor lymphocytes in HSCT for hematologic malignancies. Blood. 2007;109:4708–4715
  146. Bonini C, Ferrari G, Verzeletti S, Servida P, Zappone E, Ruggieri L, et al. HSV-TK gene transfer into donor lymphocytes for control of allogeneic graft-versus-leukemia. Science. 1997;276:1719–1724
  147. Singh H, Serrano LM, Pfeiffer T, Olivares S, McNamara G, Smith DD, et al. Combining adoptive cellular and immunocytokine therapies to improve treatment of B-lineage malignancy. Cancer Res. 2007;67:2872–2880
  148. von Andrian UH, Mackay CR. T-cell function and migration (Two sides of the same coin). N Engl J Med. 2000;343:1020–1034
  149. Ochsenbein AF, Klenerman P, Karrer U, Ludewig B, Pericin M, Hengartner H, et al. Immune surveillance against a solid tumor fails because of immunological ignorance. Proc Natl Acad Sci U S A. 1999;96:2233–2238
  150. Gajewski TF, Meng Y, Blank C, Brown I, Kacha A, Kline J, et al. Immune resistance orchestrated by the tumor microenvironment. Immunol Rev. 2006;213:131–145
  151. Manabe A, Murti KG, Coustan-Smith E, Kumagai M, Behm FG, Raimondi SC, et al. Adhesion-dependent survival of normal and leukemic human B lymphoblasts on bone marrow stromal cells. Blood. 1994;83:758–766
  152. Iwamoto S, Mihara K, Downing JR, Pui CH, Campana D. Mesenchymal cells regulate the response of acute lymphoblastic leukemia cells to asparaginase. J Clin Invest. 2007;117:1049–1057
  153. Horowitz MM, Gale RP, Sondel PM, Goldman JM, Kersey J, Kolb HJ, et al. Graft-versus-leukemia reactions after bone marrow transplantation. Blood. 1990;75:555–562
  154. Bleakley M, Riddell SR. Molecules and mechanisms of the graft-versus-leukaemia effect. Nat Rev Cancer. 2004;4:371–380
  155. Falkenburg JHF, Goselink HM, van der Harst D, van Luxemburg-Heijs SA, Kooy-Winkelaar YM, Faber LM, et al. Growth inhibition of clonogenic leukemic precursor cells by minor histocompatibility antigen-specific cytotoxic T lymphocytes. J Exp Med. 1991;174:27–33
  156. Dolstra H, Fredrix H, Preijers F, Goulmy E, Figdor CG, de Witte TM, et al. Recognition of B cell leukemia-associated minor Histocompatibility antigens by CTL. J Immunol. 1997;158:560–656
  157. Dolstra H, Fredrix H, Maas F, Coulie PG, Brasseur F, Mensink E, et al. A human minor histocompatibility antigen specific for B cell acute lmyphoblastic leukemia. J Exp Med. 1999;189:301–308
  158. Sandmaier BM, Mackinnon S, Childs RW. Reduced intensity conditioning for allogeneic hematopoietic cell transplantation: current perspectives. Biol Blood Marrow Transplant. 2007;13(1):87–97
  159. Godder KT, Henslee-Downey PJ, Mehta J, Park BS, Chiang KY, Abhyankar S, et al. Long term disease-free survival in acute leukemia patients recovering with increased gammadelta T cells after partially mismatched related donor bone marrow transplantation. Bone Marrow Transplant. 2007;39:751–757
  160. Fais F, Tenca C, Cimino G, Coletti V, Zanardi S, Bagnara D, et al. CD1d expression on B-precursor acute lymphoblastic leukemia subsets with poor prognosis. Leukemia. 2005;19:551–556
  161. Smyth MJ, Thia KY, Street SE, Cretney E, Trapani JA, Taniguchi M, et al. Differential tumor surveillance by natural killer (NK) and NKT cells. J Exp Med. 2000;191:661–668
  162. Kolb HJ, Schattenberg A, Goldman JM, Hertenstein B, Jacobsen N, Arcese W, et al. Graft-versus-leukemia effect of donor lymphocyte transfusions in marrow grafted patients (European Group for Blood and Marrow Transplantation Working Party Chronic Leukemia). Blood. 1995;86:2041–2050
  163. Tiribelli M, Sperotto A, Candoni A, Simeone E, Buttignol S, Fanin R. Nilotinib and donor lymphocyte infusion in the treatment of Philadelphia-positive acute lymphoblastic leukemia (Ph+ ALL) relapsing after allogeneic stem cell transplantation and resistant to imatinib. Leuk Res. In press.
  164. Melero I, Hervas-Stubbs S, Glennie M, Pardoll DM, Chen L. Immunostimulatory monoclonal antibodies for cancer therapy. Nat Rev Cancer. 2007;7:95–106
  165. Moccia A, Ghielmini M. Monoclonal antibodies for the treatment of hematologic malignancies: schedule and maintenance therapy. Semin Hematol. 2008;45:75–84
  166. Tsimberidou AM, Giles FJ, Estey E, O'Brien S, Keating MJ, Kantarjian HM. The role of gemtuzumab ozogamicin in acute leukaemia therapy. Br J Haematol. 2006;132:398–409
  167. Rai KR. Novel therapeutic strategies with alemtuzumab for chronic lymphocytic leukemia. Semin Oncol. 2006;33:S15–S22
  168. White CA. Radioimmunotherapy in non-Hodgkin's lymphoma: focus on 90Y-ibritumomab tiuxetan (Zevalin). J Exp Ther Oncol. 2004;4:305–310
  169. Vose JM. Bexxar: novel radioimmunotherapy for the treatment of low-grade and transformed low-grade non-Hodgkin's lymphoma. Oncologist. 2004;9:160–172
  170. Piloto O, Nguyen B, Huso D, Kim KT, Li Y, Witte L, et al. IMC-EB10, an anti-FLT3 monoclonal antibody, prolongs survival and reduces nonobese diabetic/severe combined immunodeficient engraftment of some acute lymphoblastic leukemia cell lines and primary leukemic samples. Cancer Res. 2006;66:4843–4851
  171. Dijoseph JF, Dougher MM, Armellino DC, Evans DY, Damle NK. Therapeutic potential of CD22-specific antibody-targeted chemotherapy using inotuzumab ozogamicin (CMC-544) for the treatment of acute lymphoblastic leukemia. Leukemia. 2007;21:2240–2245
  172. Bieber MM, Twist CJ, Bhat NM, Teng NN. Effects of human monoclonal antibody 216 on B-progenitor acute lymphoblastic leukemia in vitro. Pediatr Blood Cancer. 2007;48:380–386
  173. Arnon TI, Markel G, Bar-Ilan A, Hanna J, Fima E, Benchetrit F, et al. Harnessing soluble NK cell killer receptors for the generation of novel cancer immune therapy. PLoS ONE. 2008;3:e2150
  174. Lum LG, Davol PA, Lee RJ. The new face of bispecific antibodies: targeting cancer and much more. Exp Hematol. 2006;34:1–6
  175. Takahashi H, Furukawa T, Yano T, Sato N, Takizawa J, Kurasaki T, et al. Identification of an overexpressed gene, HSPA4L, the product of which can provoke prevalent humoral immune responses in leukemia patients. Exp Hematol. 2007;35:1091–1099
  176. Gudowius S, Recker K, Laws HJ, Dirksen U, Tröger A, Wieczorek U, et al. Identification of candidate target antigens for antibody-based immunotherapy in childhood B-cell precursor ALL. Klin Padiatr. 2006;218:327–333
  177. Thomas DA, Faderl S, O'Brien S, Bueso-Ramos C, Cortes J, Garcia-Manero G, et al. Chemoimmunotherapy with hyper-CVAD plus rituximab for the treatment of adult Burkitt and Burkitt-type lymphoma or acute lymphoblastic leukemia. Cancer. 2006;106:1569–1580
  178. Kebriaei P, Saliba RM, Ma C, Ippoliti C, Couriel DR, de Lima M, et al. Allogeneic hematopoietic stem cell transplantation after rituximab-containing myeloablative preparative regimen for acute lymphoblastic leukemia. Bone Marrow Transplant. 2006;38:203–209
  179. Zenz T, Glatting G, Schlenk RF, Buchmann I, Döhner H, Reske SN, et al. Targeted marrow irradiation with radioactively labeled anti-CD66 monoclonal antibody prior to allogeneic stem cell transplantation for patients with leukemia: results of a phase I-II study. Haematologica. 2006;91:285–286
  180. Dannull J, Su Z, Rizzieri D, Yang BK, Coleman D, Yancey D, et al. Enhancement of vaccine-mediated antitumor immunity in cancer patients after depletion of regulatory T cells. J Clin Invest. 2005;115:3623–3633
  181. Quezada SA, Peggs KS, Curran MA, Allison JP. CTLA4 blockade and GM-CSF combination immunotherapy alters the intratumor balance of effector and regulatory T cells. J Clin Invest. 2006;116:1935–1945
  182. Ribas A, Hanson DC, Noe DA, Millham R, Guyot DJ, Bernstein SH, et al. Tremelimumab (CP-675,206), a cytotoxic T lymphocyte associated antigen 4 blocking monoclonal antibody in clinical development for patients with cancer. Oncologist. 2007;12:873–883
  183. Fiorentino S, Chopin M, Dastot H, Boissel N, Reboul M, Legrès L, et al. Disruption of T cell regulatory pathways is necessary for immunotherapeutic cure of T cell acute lymphoblastic leukemia in mice. Eur Cytokine Netw. 2005;16:300–308
  184. Porgador A, Mandelboim O, Restifo NP, Strominger JL. Natural killer cell lines kill autologous beta2-microglobulin-deficient melanoma cells: implications for cancer immunotherapy. Proc Natl Acad Sci U S A. 1997;94:131401–131405
  185. Gruber TA, Skelton DC, Kohn DB. Requirement for NK cells in CD40 ligand-mediated rejection of Philadelphia chromosome-positive acute lymphoblastic leukemia cells. J Immunol. 2002;168:73–80
  186. Siegler U, Kalberer CP, Nowbakht P, Sendelov S, Meyer-Monard S, Wodnar-Filipowicz A. Activated natural killer cells from patients with acute myeloid leukemia are cytotoxic against autologous leukemic blasts in NOD/SCID mice. Leukemia. 2005;19:2215–2222
  187. Ruggeri L, Capanni M, Urbani E, Perruccio K, Schlomchik WD, Tosti A, et al. Effectiveness of donor natural killer cell alloreactivity in mismatched hematopoietic transplants. Science. 2002;295:2097–2100
  188. Caligiuri MA. Human natural killer cells. Blood. 2008;112:461–469
  189. Nolte-'t Hoen EN, Almeida CR, Cohen NR, Nedvetzki S, Yarwood H, Davis DM. Increased surveillance of cells in mitosis by human NK cells suggests a novel strategy for limiting tumor growth and viral replication. Blood. 2007;109:670–673
  190. Gasser S, Orsulic S, Brown EJ, Raulet DH. The DNA damage pathway regulates innate immune system ligands of the NKG2D receptor. Nature. 2005;436:1186–1190
  191. Leung W, Iyengar R, Triplett B, Turner V, Behm FG, Holladay MS, et al. Comparison of killer Ig-like receptor genotyping and phenotyping for selection of allogeneic blood stem cell donors. J Immunol. 2005;174:6540–6545
  192. Leung W, Iyengar R, Turner V, Lang P, Bader P, Conn P, et al. Determinants of antileukemia effects of allogeneic NK cells. J Immunol. 2004;172:644–650
  193. Hsu KC, Gooley T, Malkki M, Pinto-Agnello C, Dupont B, Bignon JD, et al. KIR ligands and prediction of relapse after unrelated donor hematopoietic cell transplantation for hematologic malignancy. Biol Blood Marrow Transplant. 2006;12:828–836
  194. Hsu KC, Keever-Taylor CA, Wilton A, Pinto C, Heller G, Arkun K, et al. Improved outcome in HLA-identical sibling hematopoietic stem-cell transplantation for acute myelogenous leukemia predicted by KIR and HLA genotypes. Blood. 2005;105:4878–4884
  195. Leung W, Handgretinger R, Iyengar R, Turner V, Holladay MS, Hale GA. Inhibitory KIR-HLA receptor-ligand mismatch in autologous haematopoietic stem cell transplantation for solid tumour and lymphoma. Br J Cancer. 2007;97:539–542
  196. Iyengar R, Handgretinger R, Babarin-Dorner A, Leimig T, Otto M, Geiger TL, et al. Purification of human natural killer cells using a clinical-scale immunomagnetic method. Cytotherapy. 2003;5:479–484
  197. Leung W, Iyengar R, Leimig T, Holladay MS, Houston J, Handgretinger R. Phenotype and function of human natural killer cells purified by using a clinical-scale immunomagnetic method. Cancer Immunol Immunother. 2005;54:389–394
  198. Imai C, Iwamoto S, Campana D. Genetic modification of primary natural killer cells overcomes inhibitory signals and induces specific killing of leukemic cells. Blood. 2005;106:376–383
  199. Marin V, Kakuda H, Dander E, Imai C, Campana D, Biondi A, et al. Enhancement of the anti-leukemic activity of cytokine induced killer cells with an anti-CD19 chimeric receptor delivering a 4-1BB-zeta activating signal. Exp Hematol. 2007;35:1388–1397
  200. Imai C, Mihara K, Andreansky M, Nicholson IC, Pui CH, Geiger TL, et al. Chimeric receptors with 4-1BB signaling capacity provoke potent cytotoxicity against acute lymphoblastic leukemia. Leukemia. 2004;18:676–684
  201. Marin V, Dander E, Biagi E, Introna M, Fazio G, Biondi A, et al. Characterization of in vitro migratory properties of anti-CD19 chimeric receptor-redirected CIK cells for their potential use in B-ALL immunotherapy. Exp Hematol. 2006;34:1219–1229
  202. Seya T, Akazawa T, Uehori J, Matsumoto M, Azuma I, Toyoshima K. Role of toll-like receptors and their adaptors in adjuvant immunotherapy for cancer. Anticancer Res. 2003;23:4369–4376
  203. Heckelsmiller K, Rall K, Beck S, Schlamp A, Seiderer J, Jahrsdorfer B, et al Peritumoral CpG DNA elicits a coordinated response of CD8 T cells and innate effectors to cure established tumors in a murine colon carcinoma model. J Immunol. 2002;169:3892–3899
  204. Wagtmann N, Andre P, Zahn S, Spee P, Anfossi N, Gauthier L, et al. Anti-KIR (1-7F9): a fully human monoclonal antibody (mAb) that blocks KIR2DL1, 2 and 3, promoting natural killer (NK) cell-mediated lysis of tumor cells in vitro and in vivo [abstract]. Blood. 2007;110:582a
  205. Gruber TA, Skelton DC, Kohn DB. Recombinant murine interleukin-12 elicits potent antileukemic immune responses in a murine model of Philadelphia chromosome-positive acute lymphoblastic leukemia. Cancer Gene Ther. 2005;12:818–824

 Supported in part by National Institutes of Health Grant No. P30CA21765-24, the Assisi Foundation of Memphis, and the American Lebanese Syrian Associated Charities (ALSAC).

PII: S0037-1963(08)00147-9

doi: 10.1053/j.seminhematol.2008.09.004

Seminars in Hematology
Volume 46, Issue 1 , Pages 89-99 , January 2009