Current strategies in immunotherapy for acute myeloid leukemia

Immunotherapy

Volumn 5, Issue 1, 2013, Pages 63-78

  Lichtenegger, Felix S ^a   Schnorfeil, Frauke M ^a,b   Hiddemann, Wolfgang ^a,c   Subklewe, Marion ^a,b  

^a LUDWIG MAXIMILIANS UNIVERSITY   (Germany)

^b Clinical Co operation Group Immunotherapy at the Helmholtz Institute Munich   (Germany)

^c Clinical Co operation Group Leukemia at the Helmholtz Institute Munich   (Germany)

Author keywords

acute myeloid leukemia; adoptive cellular therapy; chimeric antigen receptor; dendritic cell vaccination; gemtuzumab ozogamicin; immunotherapy; monoclonal antibody; peptide vaccination; TCR transgenic T cell

Indexed keywords

CYTOKINE; GEMTUZUMAB OZOGAMICIN; GRANULOCYTE MACROPHAGE COLONY STIMULATING FACTOR; LEUKEMIA ANTIGEN; MONOCLONAL ANTIBODY; TUMOR ANTIGEN;

ACUTE GRANULOCYTIC LEUKEMIA; ADOPTIVE TRANSFER; CLINICAL TRIAL (TOPIC); DENDRITIC CELL; FOLLOW UP; HEMATOPOIETIC STEM CELL TRANSPLANTATION; HUMAN; IMMUNOTHERAPY; LEUKEMIA CELL; NATURAL KILLER CELL; PRIORITY JOURNAL; REVIEW; T LYMPHOCYTE; VACCINATION;

ANTIBODIES, MONOCLONAL, MURINE-DERIVED; CYTOKINES; DENDRITIC CELLS; HEMATOPOIETIC STEM CELL TRANSPLANTATION; HUMANS; IMMUNOTHERAPY; IMMUNOTHERAPY, ADOPTIVE; LEUKEMIA, MYELOID, ACUTE; T-LYMPHOCYTES;

EID: 84871575120     PISSN: 1750743X     EISSN: 17507448     Source Type: Journal    
DOI: 10.2217/imt.12.145     Document Type: Review

References (130)

1. Smits EL, Berneman ZN, Van Tendeloo VF. Immunotherapy of acute myeloid leukemia: Current approaches. Oncologist 14, 240-252 (2009).
2. Barrett AJ, Le Blanc K. Immunotherapy prospects for acute myeloid leukaemia. Clin. Exp. Immunol. 161, 223-232 (2010).
3. Kadowaki N, Kitawaki T. Recent advance in antigen-specific immunotherapy for acute myeloid leukemia. Clin. Dev. Immunol. 2011, 104926 (2011).
4. Smits EL, Lee C, Hardwick N et al. Clinical evaluation of cellular immunotherapy in acute myeloid leukaemia. Cancer Immunol. Immunother. 60, 757-769 (2011).
5. Mellman I, Coukos G, Dranoff G. Cancer immunotherapy comes of age. Nature 480, 480-489 (2011).
6. Rescigno M, Avogadri F, Curigliano G. Challenges and prospects of immunotherapy as cancer treatment. Biochim. Biophys. Acta 1776, 108-123 (2007).
7. Fong L, Small EJ. Anti-cytotoxic T lymphocyte antigen 4 antibody: The first in an emerging class of immunomodulatory antibodies for cancer treatment. J. Clin. Oncol. 26, 5275-5283 (2008).
8. Lion E, Willemen Y, Berneman ZN, Van Tendeloo VF, Smits EL. Natural killer cell immune escape in acute myeloid leukemia. Leukemia 26, 2019-2026 (2012).
9. Sanchez-Correa B, Morgado S, Gayoso I et al. Human NK cells in acute myeloid leukaemia patients: Analysis of NK cell-activating receptors and their ligands. Cancer Immunol. Immunother. 60, 1195-1205 (2011).
10. Baessler T, Krusch M, Schmiedel BJ et al. Glucocorticoid-induced tumor necrosis factor receptor-related protein ligand subverts immunosurveillance of acute myeloid leukemia in humans. Cancer Res. 69, 1037-1045 (2009).
11. Baessler T, Charton JE, Schmiedel BJ et al. CD137 ligand mediates opposite effects in human and mouse NK cells and impairs NK-cell reactivity against human acute myeloid leukemia cells. Blood 115, 3058-3069 (2010).
12. Coles SJ, Wang EC, Man S et al. CD200 expression suppresses natural killer cell function and directly inhibits patient anti-tumor response in acute myeloid leukemia. Leukemia 25, 792-799 (2011).
13. Chamuleau ME, Ossenkoppele GJ, van Rhenen A et al. High TRAILR3 expression on leukemic blasts is associated with poor outcome and induces apoptosis-resistance which can be overcome by targeting TRAILR2. Leuk. Res. 35, 741-749 (2011).
14. Ragusa M, Avola G, Angelica R et al. Expression profile and specific network features of the apoptotic machinery explain relapse of acute myeloid leukemia after chemotherapy. BMC Cancer 10, 377 (2010).
15. Le Dieu R, Taussig DC, Ramsay AG et al. Peripheral blood T cells in acute myeloid leukemia (AML) patients at diagnosis have abnormal phenotype and genotype and form defective immune synapses with AML blasts. Blood 114, 3909-3916 (2009).
16. Ustun C, Miller JS, Munn DH, Weisdorf DJ, Blazar BR. Regulatory T cells in acute myelogenous leukemia: Is it time for immunomodulation? Blood 118, 5084-5095 (2011).
17. van Luijn MM, van den Ancker W, Chamuleau ME, Ossenkoppele GJ, van Ham SM, van de Loosdrecht AA. Impaired antigen presentation in neoplasia: Basic mechanisms and implications for acute myeloid leukemia. Immunotherapy 2, 85-97 (2010).
18. van Luijn MM, van den Ancker W, Chamuleau ME et al. Absence of class II-associated invariant chain peptide on leukemic blasts of patients promotes activation of autologous leukemia-reactive CD4+ T cells. Cancer Res. 71, 2507-2517 (2011).
19. Norde WJ, Hobo W, van der Voort R, Dolstra H. Coinhibitory molecules in hematologic malignancies: Targets for therapeutic intervention. Blood 120, 728-736 (2012).
20. Scholl N, Loibl J, Kremser A et al. The role of soluble and cell-surface expressed 4-1BB ligand in patients with malignant hemopoietic disorders. Leuk. Lymphoma 50, 427-436 (2009).
21. Curti A, Aluigi M, Pandolfi S et al. Acute myeloid leukemia cells constitutively express the immunoregulatory enzyme indoleamine 2,3-dioxygenase. Leukemia 21, 353-355 (2007).
22. Aurelius J, Thorén FB, Akhiani A A et al. Monocytic AML cells inactivate antileukemic lymphocytes: Role of NADPH oxidase/gp91(phox) expression and the PARP-1/PAR pathway of apoptosis. Blood 119, 5832-5837 (2012).
23. Zitvogel L, Apetoh L, Ghiringhelli F, Kroemer G. Immunological aspects of cancer chemotherapy. Nat. Rev. Immunol. 8, 59-73 (2008).
24. Obeid M, Tesniere A, Ghiringhelli F et al. Calreticulin exposure dictates the immunogenicity of cancer cell death. Nat. Med. 13, 54-61 (2007).
25. Blum W, Klisovic RB, Becker H et al. Dose escalation of lenalidomide in relapsed or refractory acute leukemias. J. Clin. Oncol. 28, 4919-4925 (2010).
26. Almstedt M, Blagitko-Dorfs N, Duque- Afonso J et al. The DNA demethylating agent 5aza-2́deoxycytidine induces expression of NYESO1 and other cancer/ testis antigens in myeloid leukemia cells. Leuk. Res. 34, 899-905 (2010).
27. Goodyear OC, Dennis M, Jilani NY et al. Azacitidine augments expansion of regulatory T cells after allogeneic stem cell transplantation in patients with acute myeloid leukemia (AML). Blood 119, 3361-3369 (2012).
28. Cheever MA, Allison JP, Ferris AS et al. The prioritization of cancer antigens: A national cancer institute pilot project for the acceleration of translational research. Clin. Cancer Res. 15, 5323-5337 (2009).
29. Anguille S, Van Tendeloo VF, Berneman ZN. Leukemia-associated antigens and their relevance to the immunotherapy of acute myeloid leukemia. Leukemia 26, 2186-2196 (2012).
30. Graf C, Heidel F, Tenzer S et al. A neoepitope generated by an FLT3 internal tandem duplication (FLT3-ITD) is recognized by leukemia-reactive autologous CD8+ T cells. Blood 109, 2985-2988 (2007).
31. Greiner J, Ono Y, Hofmann S et al. Mutated regions of nucleophosmin 1 elicit both CD4+ and CD8+ T cell responses in patients with acute myeloid leukemia. Blood 120, 1282-1289 (2012).
32. Van Driessche A, Berneman ZN, Van Tendeloo VF. Active specific immunotherapy targeting the Wilms' tumor protein 1 (WT1) for patients with hematological malignancies and solid tumors: Lessons from early clinical trials. Oncologist 17, 250-259 (2012).
33. Majeti R, Becker MW, Tian Q et al. Dysregulated gene expression networks in human acute myelogenous leukemia stem cells. Proc. Natl Acad. Sci. USA 106, 3396-3401 (2009).
34. Van Tendeloo VF, Van de Velde A, Van Driessche A et al. Induction of complete and molecular remissions in acute myeloid leukemia by Wilms' tumor 1 antigen-targeted dendritic cell vaccination. Proc. Natl Acad. Sci. USA 107, 13824-13829 (2010).
35. Gal H, Amariglio N, Trakhtenbrot L et al. Gene expression profiles of AML derived stem cells; similarity to hematopoietic stem cells. Leukemia 20, 2147-2154 (2006).
36. Ochsenreither S, Majeti R, Schmitt T et al. Cyclin-A1 represents a new immunogenic targetable antigen expressed in acute myeloid leukemia stem cells with characteristics of a cancer-testis antigen. Blood 119, 5492-5501 (2012).
37. Gerber JM, Qin L, Kowalski J et al. Characterization of chronic myeloid leukemia stem cells. Am. J. Hematol. 86, 31-37 (2011).
38. Rezvani K, Yong AS, Tawab A et al. Ex vivo characterization of polyclonal memory CD8+ T cell responses to PRAME-specific peptides in patients with acute lymphoblastic leukemia and acute and chronic myeloid leukemia. Blood 113, 2245-2255 (2009).
39. Amir AL, van der Steen DM, van Loenen MM et al. PRAME-specific Allo-HLA-restricted T cells with potent antitumor reactivity useful for therapeutic T cell receptor gene transfer. Clin. Cancer Res. 17, 5615-5625 (2011).
40. Gialeli CH, Kletsas D, Mavroudis D, Kalofonos HP, Tzanakakis GN, Karamanos NK. Targeting epidermal growth factor receptor in solid tumors: Critical evaluation of the biological importance of therapeutic monoclonal antibodies. Curr. Med. Chem. 16, 3797-3804 (2009).
41. Hodi FS, O'Day SJ, McDermott DF et al. Improved survival with ipilimumab in patients with metastatic melanoma. N. Engl. J. Med. 363, 711-723 (2010).
42. Maloney DG. Anti-CD20 antibody therapy for B cell lymphomas. N. Engl. J. Med. 366, 2008-2016 (2012).
43. Walter RB, Appelbaum FR, Estey EH, Bernstein ID. Acute myeloid leukemia stem cells and CD33-targeted immunotherapy. Blood 119, 6198-6208 (2012).
44. Feldman EJ, Brandwein J, Stone R et al. Phase III randomized multicenter study of a humanized anti-CD33 monoclonal antibody, lintuzumab, in combination with chemotherapy, versus chemotherapy alone in patients with refractory or first-relapsed acute myeloid leukemia. J. Clin. Oncol. 23, 4110-4116 (2005).
45. Rosenblat TL, McDevitt MR, Mulford DA et al. Sequential cytarabine and α-particle immunotherapy with bismuth- 213 lintuzumab (HuM195) for acute myeloid leukemia. Clin. Cancer Res. 16, 5303-5311 (2010).
46. Lapusan S, Vidriales MB, Thomas X et al. Phase I studies of AVE9633, an anti-CD33 antibody-maytansinoid conjugate, in adult patients with relapsed/refractory acute myeloid leukemia. Invest. New Drugs 30, 1121-1131 (2012).
47. Bross PF, Beitz J, Chen G et al. Approval summary: Gemtuzumab ozogamicin in relapsed acute myeloid leukemia. Clin. Cancer Res. 7, 1490-1496 (2001).
48. Petersdorf S, Kopecky K, Stuart RK et al. Preliminary results of Southwest Oncology Group Study S0106: An international intergroup Phase 3 randomized trial comparing the addition of gemtuzumab ozogamicin to standard induction therapy versus standard induction therapy followed by a second randomization to post-consolidation gemtuzumab ozogamicin versus no additional therapy for previously untreated acute myeloid leukemia. Blood 114, Abstract 790 (2009).
49. Lo-Coco F, Cimino G, Breccia M et al. Gemtuzumab ozogamicin (Mylotarg) as a single agent for molecularly relapsed acute promyelocytic leukemia. Blood 104, 1995-1999 (2004).
50. Ravandi F, Estey E, Jones D et al. Effective treatment of acute promyelocytic leukemia with all-trans-retinoic acid, arsenic trioxide, and gemtuzumab ozogamicin. J. Clin. Oncol. 27, 504-510 (2009).
51. Burnett AK, Hills RK, Milligan D et al. Identification of patients with acute myeloblastic leukemia who benefit from the addition of gemtuzumab ozogamicin: Results of the MRC AML15 trial. J. Clin. Oncol. 29, 369-377 (2011).
52. Castaigne S, Pautas C, Terré C et al. Effect of gemtuzumab ozogamicin on survival of adult patients with de-novo acute myeloid leukaemia (ALFA-0701): A randomised, open-label, Phase 3 study. Lancet 379, 1508-1516 (2012).
53. Burnett AK, Russell NH, Hills RK et al. Addition of gemtuzumab ozogamicin to induction chemotherapy improves survival in older patients with acute myeloid leukemia. J. Clin. Oncol. 30(32), 3924-3931 (2012).
54. Amadori S, Suciu S, Stasi R et al. Gemtuzumab ozogamicin (Mylotarg) as single-agent treatment for frail patients 61 years of age and older with acute myeloid leukemia: Final results of AML15B, a Phase 2 study of the European Organisation for Research and Treatment of Cancer and Gruppo Italiano Malattie Ematologiche Dell'Adulto Leukemia groups. Leukemia 19, 1768-1773 (2005).
55. Taksin AL, Legrand O, Raffoux E et al. High efficacy and safety profile of fractionated doses of Mylotarg as induction therapy in patients with relapsed acute myeloblastic leukemia: A prospective study of the alfa group. Leukemia 21, 66-71 (2007).
56. Farhat H, Reman O, Raffoux E et al. Fractionated doses of gemtuzumab ozogamicin with escalated doses of daunorubicin and cytarabine as first acute myeloid leukemia salvage in patients aged 50-70 year old: A Phase 1/2 study of the acute leukemia French association. Am. J. Hematol. 87, 62-65 (2012).
57. Kindler T, Lipka DB, Fischer T. FLT3 as a therapeutic target in AML: Still challenging after all these years. Blood 116, 5089-5102 (2010).
58. Piloto O, Levis M, Huso D et al. Inhibitory anti-FLT3 antibodies are capable of mediating antibody-dependent cell-mediated cytotoxicity and reducing engraftment of acute myelogenous leukemia blasts in nonobese diabetic/severe combined immunodeficient mice. Cancer Res. 65, 1514-1522 (2005).
59. Hofmann M, Große-Hovest L, Nübling T et al. Generation, selection and preclinical characterization of an Fc-optimized FLT3 antibody for the treatment of myeloid leukemia. Leukemia 26, 1228-1237 (2012).
60. Majeti R. Monoclonal antibody therapy directed against human acute myeloid leukemia stem cells. Oncogene 30, 1009-1019 (2011).
61. Zhao X, Singh S, Pardoux C et al. Targeting C-type lectin-like molecule-1 for antibody-mediated immunotherapy in acute myeloid leukemia. Haematologica 95, 71-78 (2010).
62. Jin L, Hope KJ, Zhai Q, Smadja-Joffe F, Dick JE. Targeting of CD44 eradicates human acute myeloid leukemic stem cells. Nat. Med. 12, 1167-1174 (2006).
63. Majeti R, Chao MP, Alizadeh AA et al. CD47 is an adverse prognostic factor and therapeutic antibody target on human acute myeloid leukemia stem cells. Cell 138, 286-299 (2009).
64. Jin L, Lee EM, Ramshaw HS et al. Monoclonal antibody-mediated targeting of CD123, IL 3 receptor α chain, eliminates human acute myeloid leukemic stem cells. Cell Stem Cell 5, 31-42 (2009).
65. Stein C, Kellner C, Kügler M et al. Novel conjugates of single-chain Fv antibody fragments specific for stem cell antigen CD123 mediate potent death of acute myeloid leukaemia cells. Br. J. Haematol. 148, 879-889 (2010).
66. Lipson EJ, Drake CG. Ipilimumab: An anti-CTLA-4 antibody for metastatic melanoma. Clin. Cancer Res. 17, 6958-6962 (2011).
67. Zhong RK, Loken M, Lane TA, Ball ED. CTLA4 blockade by a human MAb enhances the capacity of AML-derived DC to induce T cell responses against AML cells in an autologous culture system. Cytotherapy 8, 3-12 (2006).
68. Bashey A, Medina B, Corringham S et al. CTLA4 blockade with ipilimumab to treat relapse of malignancy after allogeneic hematopoietic cell transplantation. Blood 113, 1581-1588 (2009).
69. Zhang L, Gajewski TF, Kline J. PD-1/PD-L1 interactions inhibit antitumor immune responses in a murine acute myeloid leukemia model. Blood 114, 1545-1552 (2009).
70. Zhou Q, Munger ME, Highfill SL et al. Program death 1 signaling and regulatory T cells collaborate to resist the function of adoptively transferred cytotoxic T lymphocytes in advanced acute myeloid leukemia. Blood 116, 2484-2493 (2010).
71. Zhou Q, Munger ME, Veenstra RG et al. Coexpression of Tim-3 and PD-1 identifies a CD8+ T cell exhaustion phenotype in mice with disseminated acute myelogenous leukemia. Blood 117, 4501-4510 (2011).
72. Berger R, Rotem-Yehudar R, Slama G et al. Phase I safety and pharmacokinetic study of CT011, a humanized antibody interacting with PD1, in patients with advanced hematologic malignancies. Clin. Cancer Res. 14, 3044-3051 (2008).
73. Lanier LL. NK cell recognition. Annu. Rev. Immunol. 23, 225-274 (2005).
74. Venstrom JM, Pittari G, Gooley TA et al. HLAC-dependent prevention of leukemia relapse by donor activating KIR2DS1. N. Engl. J. Med. 367, 805-816 (2012).
75. 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 105, 3051-3057 (2005).
76. Guo M, Hu KX, Yu CL et al. Infusion of HLA-mismatched peripheral blood stem cells improves the outcome of chemotherapy for acute myeloid leukemia in elderly patients. Blood 117, 936-941 (2011).
77. Restifo NP, Dudley ME, Rosenberg SA. Adoptive immunotherapy for cancer: harnessing the T cell response. Nat. Rev. Immunol. 12, 269-281 (2012).
78. Kolb HJ, Mittermüller J, Clemm C et al. Donor leukocyte transfusions for treatment of recurrent chronic myelogenous leukemia in marrow transplant patients. Blood 76, 2462-2465 (1990).
79. Collins RH, Shpilberg O, Drobyski WR et al. Donor leukocyte infusions in 140 patients with relapsed malignancy after allogeneic bone marrow transplantation. J. Clin. Oncol. 15, 433-444 (1997).
80. Schmid C, Labopin M, Nagler A et al. Donor lymphocyte infusion in the treatment of first hematological relapse after allogeneic stem-cell transplantation in adults with acute myeloid leukemia: A retrospective risk factors analysis and comparison with other strategies by the EBMT Acute Leukemia Working Party. J. Clin. Oncol. 25, 4938-4945 (2007).
81. Soiffer RJ. Donor lymphocyte infusions for acute myeloid leukaemia. Best Pract. Res. Clin. Haematol. 21, 455-466 (2008).
82. 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. 163, 507-513 (1999).
83. Morgan RA, Dudley ME, Wunderlich JR et al. Cancer regression in patients after transfer of genetically engineered lymphocytes. Science 314, 126-129 (2006).
84. 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 106, 3062-3067 (2005).
85. Perro M, Tsang J, Xue SA et al. Generation of multi-functional antigen-specific human T cells by lentiviral TCR gene transfer. Gene Ther. 17, 721-732 (2010).
86. 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. 118, 294-305 (2008).
87. 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 γ or ζ subunits of the immunoglobulin and T cell receptors. Proc. Natl Acad. Sci. USA 90, 720-724 (1993).
88. Jena B, Dotti G, Cooper LJ. Redirecting T cell specificity by introducing a tumor-specific chimeric antigen receptor. Blood 116, 1035-1044 (2010).
89. Uttenthal BJ, Chua I, Morris EC, Stauss HJ. Challenges in T cell receptor gene therapy. J. Gene Med. 14, 386-399 (2012).
90. Porter DL, Levine BL, Kalos M, Bagg A, June CH. Chimeric antigen receptor-modified T cells in chronic lymphoid leukemia. N. Engl. J. Med. 365, 725-733 (2011).
91. Kochenderfer JN, Dudley ME, Feldman SA et al. B cell depletion and remissions of malignancy along with cytokine-associated toxicity in a clinical trial of anti-CD19 chimeric-antigen-receptor-transduced T cells. Blood 119, 2709-2720 (2012).
92. Baer MR, George SL, Caligiuri MA et al. Low-dose interleukin 2 immunotherapy does not improve outcome of patients age 60 years and older with acute myeloid leukemia in first complete remission: Cancer and Leukemia Group B Study 9720. J. Clin. Oncol. 26, 4934-4939 (2008).
93. Brune M, Castaigne S, Catalano J et al. Improved leukemia-free survival after postconsolidation immunotherapy with histamine dihydrochloride and interleukin 2 in acute myeloid leukemia: Results of a randomized Phase 3 trial. Blood 108, 88-96 (2006).
94. Koreth J, Matsuoka K, Kim HT et al. Interleukin 2 and regulatory T cells in graft-versus-host disease. N. Engl. J. Med. 365, 2055-2066 (2011).
95. Cheng G, Yu A, Malek TR. T cell tolerance and the multi-functional role of IL 2R signaling in T-regulatory cells. Immunol. Rev. 241, 63-76 (2011).
96. Waldmann TA, Lugli E, Roederer M et al. Safety (toxicity), pharmacokinetics, immunogenicity, and impact on elements of the normal immune system of recombinant human IL 15 in rhesus macaques. Blood 117, 4787-4795 (2011).
97. 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 111, 236-242 (2008).
98. Rezvani K, Yong AS, Mielke S et al. Repeated PR1 and WT1 peptide vaccination in Montanide-adjuvant fails to induce sustained high-avidity, epitope-specific CD8+ T cells in myeloid malignancies. Haematologica 96, 432-440 (2011).
99. Keilholz U, Letsch A, Busse A et al. A clinical and immunologic Phase 2 trial of Wilms tumor gene product 1 (WT1) peptide vaccination in patients with AML and MDS. Blood 113, 6541-6548 (2009).
100. Ochsenreither S, Fusi A, Busse A et al. "Wilms Tumor Protein 1" (WT1) peptide vaccination-induced complete remission in a patient with acute myeloid leukemia is accompanied by the emergence of a predominant T cell clone both in blood and bone marrow. J. Immunother. 34, 85-91 (2011).
101. Ochsenreither S, Fusi A, Geikowski A et al. Wilms' tumor protein 1 (WT1) peptide vaccination in AML patients: Predominant TCR CDR3β sequence associated with remission in one patient is detectable in other vaccinated patients. Cancer Immunol. Immunother. 61, 313-322 (2012).
102. Schmitt M, Schmitt A, Rojewski MT et al. RHAMMR3 peptide vaccination in patients with acute myeloid leukemia, myelodysplastic syndrome, and multiple myeloma elicits immunologic and clinical responses. Blood 111, 1357-1365 (2008).
103. Greiner J, Schmitt A, Giannopoulos K et al. High-dose RHAMMR3 peptide vaccination for patients with acute myeloid leukemia, myelodysplastic syndrome and multiple myeloma. Haematologica 95, 1191-1197 (2010).
104. Kuball J, de Boer K, Wagner E et al. Pitfalls of vaccinations with WT1-, proteinase3- and MUC1-derived peptides in combination with MontanideISA51 and CpG7909. Cancer Immunol. Immunother. 60, 161-171 (2011).
105. Maslak PG, Dao T, Krug LM et al. Vaccination with synthetic analog peptides derived from WT1 oncoprotein induces T cell responses in patients with complete remission from acute myeloid leukemia. Blood 116, 171-179 (2010).
106. Borrello IM, Levitsky HI, Stock W et al. Granulocyte-macrophage colony-stimulating factor (GM-CSF)-secreting cellular immunotherapy in combination with autologous stem cell transplantation (ASCT) as postremission therapy for acute myeloid leukemia (AML). Blood 114, 1736-1745 (2009).
107. Ingram W, Chan L, Guven H et al. Human CD80/IL2 lentivirus-transduced acute myeloid leukaemia (AML) cells promote natural killer (NK) cell activation and cytolytic activity: Implications for a Phase I clinical study. Br. J. Haematol. 145, 749-760 (2009).
108. Hardwick N, Chan L, Ingram W, Mufti G, Farzaneh F. Lytic activity against primary AML cells is stimulated in vitro by an autologous whole cell vaccine expressing IL 2 and CD80. Cancer Immunol. Immunother. 59, 379-388 (2010).
109. Kremser A, Dressig J, Grabrucker C et al. Dendritic cells (DCs) can be successfully generated from leukemic blasts in individual patients with AML or MDS: An evaluation of different methods. J. Immunother. 33, 185-199 (2010).
110. Ge W, Ma X, Li X et al. B7-H1 up-regulation on dendritic-like leukemia cells suppresses T cell immune function through modulation of IL 10/IL 12 production and generation of Treg cells. Leuk. Res. 33, 948-957 (2009).
111. Curti A, Trabanelli S, Onofri C et al. Indoleamine 2,3-dioxygenase- expressing leukemic dendritic cells impair a leukemia-specific immune response by inducing potent T regulatory cells. Haematologica 95, 2022-2030 (2010).
112. Li L, Giannopoulos K, Reinhardt P et al. Immunotherapy for patients with acute myeloid leukemia using autologous dendritic cells generated from leukemic blasts. Int. J. Oncol. 28, 855-861 (2006).
113. Roddie H, Klammer M, Thomas C et al. Phase I/II study of vaccination with dendritic-like leukaemia cells for the immunotherapy of acute myeloid leukaemia. Br. J. Haematol. 133, 152-157 (2006).
114. Draube A, Beyer M, Wolf J. Activation of autologous leukemia-specific T cells in acute myeloid leukemia: Monocyte-derived dendritic cells cocultured with leukemic blasts compared with leukemia-derived dendritic cells. Eur. J. Haematol. 81, 281-288 (2008).
115. Anguille S, Lion E, Smits E, Berneman ZN, van Tendeloo VF. Dendritic cell vaccine therapy for acute myeloid leukemia: Questions and answers. Hum. Vaccin. 7, 579-584 (2011).
116. Serrano-López J, Sanchez-Garcia J, Serrano J et al. Nonleukemic myeloid dendritic cells obtained from autologous stem cell products elicit antileukemia responses in patients with acute myeloid leukemia. Transfusion 51, 1546-1555 (2011).
117. Mohib K, Wang L. Differentiation and characterization of dendritic cells from human embryonic stem cells. Curr. Protoc. Immunol. Chapter 22, Unit22F.11 (2012).
118. van de Ven R, Reurs AW, Wijnands PG et al. Exposure of CD34+ precursors to cytostatic anthraquinone-derivatives induces rapid dendritic cell differentiation: Implications for cancer immunotherapy. Cancer Immunol. Immunother. 61, 181-191 (2012).
119. Spranger S, Frankenberger B, Schendel DJ. NOD/SCID IL 2Rg(null) mice: A preclinical model system to evaluate human dendritic cell-based vaccine strategies in vivo. J. Transl Med. 10, 30 (2012).
120. Lee JJ, Kook H, Park MS et al. Immunotherapy using autologous monocyte-derived dendritic cells pulsed with leukemic cell lysates for acute myeloid leukemia relapse after autologous peripheral blood stem cell transplantation. J. Clin. Apher. 19, 66-70 (2004).
121. Van Driessche A, Van de Velde AL, Nijs G et al. Clinical-grade manufacturing of autologous mature mRNA-electroporated dendritic cells and safety testing in acute myeloid leukemia patients in a Phase I dose-escalation clinical trial. Cytotherapy 11, 653-668 (2009).
122. Berneman ZN, Van de Velde A, Anguille S et al. WT1-targeted dendritic cell vaccination as a postremission treatment to prevent or delay relapse in acute myeloid leukemia. J. Clin. Oncol. 30, Abstract 2506 (2012).
123. Kitawaki T, Kadowaki N, Fukunaga K et al. Cross-priming of CD8(+) T cells in vivo by dendritic cells pulsed with autologous apoptotic leukemic cells in immunotherapy for elderly patients with acute myeloid leukemia. Exp. Hematol. 39, 424-433.e2 (2011).
124. Kitawaki T, Kadowaki N, Fukunaga K et al. A Phase I/IIa clinical trial of immunotherapy for elderly patients with acute myeloid leukaemia using dendritic cells co-pulsed with WT1 peptide and zoledronate. Br. J. Haematol. 153, 796-799 (2011).
125. Jonuleit H, Kuhn U, Muller G et al. Pro-inflammatory cytokines and prostaglandins induce maturation of potent immunostimulatory dendritic cells under fetal calf serum-free conditions. Eur. J. Immunol. 27, 3135-3142 (1997).
126. van den Ancker W, van Luijn MM, Ruben JM et al. Targeting Toll-like receptor 7/8 enhances uptake of apoptotic leukemic cells by monocyte-derived dendritic cells but interferes with subsequent cytokine-induced maturation. Cancer Immunol. Immunother. 60, 37-47 (2011).
127. Zobywalski A, Javorovic M, Frankenberger B et al. Generation of clinical grade dendritic cells with capacity to produce biologically active IL 12p70. J. Transl Med. 5, 18 (2007).
128. Spranger S, Javorovic M, Bürdek M et al. Generation of Th1-polarizing dendritic cells using the TLR7/8 agonist CL075. J. Immunol. 185, 738-747 (2010).
129. Lichtenegger FS, Mueller K, Otte B et al. CD86 and IL 12p70 are key players for T helper 1 polarization and natural killer cell activation by Toll-like receptor-induced dendritic cells. PLoS ONE 7, e44266 (2012).
130. Beck B, Dörfel D, Lichtenegger FS et al. Effects of TLR agonists on maturation and function of 3 day dendritic cells from AML patients in complete remission. J. Transl Med. 9, 151 (2011).