Update on Antigen-Specific Immunotherapy of Acute Myeloid Leukemia

Current Hematologic Malignancy Reports

Volumn 10, Issue 2, 2015, Pages 65-75

  Buckley, Sarah A ^a   Walter, Roland B ^a,b  

^a UNIVERSITY OF WASHINGTON   (United States)

^b USA   (United States)

Author keywords

Acute myeloid leukemia; Adoptive immunotherapy; Antibody; Antibody drug conjugate; Bispecific antibody; Chimeric antigen receptor

Indexed keywords

ANTIBODY; ANTINEOPLASTIC AGENT; CANCER VACCINE; DENDRITIC CELL VACCINE; IMMUNOMODULATING AGENT; IMMUNOTOXIN; PEPTIDE VACCINE; AMINOGLYCOSIDE; GEMTUZUMAB; MONOCLONAL ANTIBODY;

ACUTE LYMPHOBLASTIC LEUKEMIA; ACUTE MYELOBLASTIC LEUKEMIA; ADOPTIVE IMMUNOTHERAPY; ANTIGEN EXPRESSION; ANTIGEN SPECIFIC IMMUNOTHERAPY; CANCER IMMUNIZATION; CANCER IMMUNOTHERAPY; CLINICAL TRIAL (TOPIC); CYTOGENETICS; CYTOPENIA; DRUG CONJUGATION; HUMAN; IMMUNE RESPONSE; NONHUMAN; PHASE 1 CLINICAL TRIAL (TOPIC); PHASE 2 CLINICAL TRIAL (TOPIC); PHASE 3 CLINICAL TRIAL (TOPIC); PROTEIN TARGETING; RADIOIMMUNOTHERAPY; RANDOMIZED CONTROLLED TRIAL (TOPIC); REVIEW; IMMUNOLOGY; IMMUNOTHERAPY; LEUKEMIA, MYELOID, ACUTE; MOLECULARLY TARGETED THERAPY; PROCEDURES; T LYMPHOCYTE;

AMINOGLYCOSIDES; ANTIBODIES, MONOCLONAL, HUMANIZED; ANTINEOPLASTIC AGENTS; CLINICAL TRIALS AS TOPIC; HUMANS; IMMUNOTHERAPY; LEUKEMIA, MYELOID, ACUTE; MOLECULAR TARGETED THERAPY; T-LYMPHOCYTES;

EID: 84929957995     PISSN: 15588211     EISSN: 1558822X     Source Type: Journal    
DOI: 10.1007/s11899-015-0250-9     Document Type: Review

References (131)

1. Burnett A, Wetzler M, Löwenberg B. Therapeutic advances in acute myeloid leukemia. J Clin Oncol. 2011;29(5):487–94. Excellent review article on current therapeutic strategies in AML.
2. Ferrara F, Schiffer CA. Acute myeloid leukaemia in adults. Lancet. 2013;381(9865):484–95. Excellent review article on adult AML.
3. Othus M, Kantarjian H, Petersdorf S, et al. Declining rates of treatment-related mortality in patients with newly diagnosed AML given 'intense' induction regimens: a report from SWOG and MD Anderson. Leukemia. 2014;28(2):289–92.
4. Hills RK, Castaigne S, Appelbaum FR, et al. Addition of gemtuzumab ozogamicin to induction chemotherapy in adult patients with acute myeloid leukaemia: a meta-analysis of individual patient data from randomised controlled trials. Lancet Oncol. 2014;15(9):986–96. This meta-analysis of 5 randomized trials that investigated the value of GO in combination with induction chemotherapy demonstrates that GO reduces the relapse risk and improves survival primarily in patients with favorable-risk and intermediate-risk but not adverse-risk AML.
5. Gamis AS, Alonzo TA, Meshinchi S, et al. Gemtuzumab ozogamicin in children and adolescents with De Novo acute myeloid leukemia improves event-free survival by reducing relapse risk: results from the randomized phase III Children's Oncology Group trial AAML0531. J Clin Oncol. 2014;32(27):3021–32. First study demonstrating a survival benefit of GO when used in combination with induction chemotherapy in pediatric AML.
6. Walter RB, Appelbaum FR, Estey EH, Bernstein ID. Acute myeloid leukemia stem cells and CD33-targeted immunotherapy. Blood. 2012;119(26):6198–208. Review of the rationale to target CD33 in AML.
7. Laszlo GS, Estey EH, Walter RB. The past and future of CD33 as therapeutic target in acute myeloid leukemia. Blood Rev. 2014;28(4):143–53.
8. Walter RB, Press OW, Bernstein ID. Antibody-based therapeutics targeting CD33, CD45, and CD66. In: Andreef M, ed. Targeted therapy of acute myeloid leukemia. 1st ed: Springer 2015:531-58.
9. Sinclair AM, Nazarian AA, Homann O, et al. Validation of bi-specific T-cell engager (BiTE®) antibody activity in vitro and in vivo against differentially expressed cell surface targets in acute myeloid leukemia [abstract]. Haematologica. 2014;99 Suppl 1:293–4.
10. Behbehani GK, Fantl WJ, Medeiros BC, Nolan GP. Mass cytometric analysis of AML stem and early progenitor cells reveals karyotype and genotype-specific immunophenotypes that may represent targets for antibody-directed therapies [abstract]. Blood. 2014;124(21):2380.
11. Cancer Genome Atlas Research N. Genomic and epigenomic landscapes of adult de novo acute myeloid leukemia. N Engl J Med. 2013;368(22):2059–74. Landmark study demonstrating the genetic diversity and heterogeneity of human AML.
12. Anguille S, Van Tendeloo VF, Berneman ZN. Leukemia-associated antigens and their relevance to the immunotherapy of acute myeloid leukemia. Leukemia. 2012;26(10):2186–96.
13. Pollard JA, Alonzo TA, Loken M, et al. Correlation of CD33 expression level with disease characteristics and response to gemtuzumab ozogamicin containing chemotherapy in childhood AML. Blood. 2012;119(16):3705–11.
14. Krupka C, Kufer P, Kischel R, et al. CD33 target validation and sustained depletion of AML blasts in long-term cultures by the bispecific T-cell-engaging antibody AMG 330. Blood. 2014;123(3):356–65.
15. He SZ, Busfield S, Ritchie DS, et al. A phase 1 study of the safety, pharmacokinetics and anti-leukemic activity of the anti-CD123 monoclonal antibody CSL360 in relapsed, refractory or high-risk acute myeloid leukemia. Leuk Lymphoma. 2015; in press.
16. Heider K-H, Konopitzky R, Ostermann E, et al. A novel Fc-engineered antibody to CD33 with enhanced ADCC activity for treatment of AML [abstract]. Blood. 2012;120(21):1363.
17. Senyukov V, Kelton W, Mehta N, Georgiou G, Lee D. Engineering anti-AML antibodies for improved NK cell ADCC [abstract]. Blood. 2012;120(21):3629.
18. Busfield SJ, Biondo M, Wong M, et al. Targeting of acute myeloid leukemia in vitro and in vivo with an anti-CD123 mAb engineered for optimal ADCC. Leukemia. 2014;28(11):2213–21.
19. Smith BD, Roboz GJ, Walter RB, et al. First-in man, phase 1 study of CSL362 (anti-IL3Rα/anti-CD123 monoclonal antibody) in patients with CD123+ acute myeloid leukemia (AML) in CR at high risk for early relapse [abstract]. Blood. 2014;124(21):120.
20. Koerner S, Leibold J, Grosse-Hovest L, et al. Development and preclinical characterization of an Fc-optimized CD133 antibody for induction of NK cell reactivity against myeloid leukemia [abstract]. Blood. 2014;124(21):2309.
21. Salih HR, Hofmann M, Grosse-Hovest L, et al. Elimination of minimal residual disease (MRD) in AML patients with a novel Fc-optimized FLT3 antibody (4G8-SDIEM) [abstract]. Blood. 2013;122(21):1454.
22. Dos Santos C, Xiaochuan S, Chenghui Z, et al. Anti-leukemic activity of daratumumab in acute myeloid leukemia cells and patient-derived xenografts [abstract]. Blood. 2014;124(21):2312.
23. Krupka C, Jansen A, Lassmann I, et al. Targeting AML using an Fc-engineered BST1/CD157 monoclonal antibody [abstract]. Blood. 2014;124(21):987.
24. Venditti A, Buccisano F, Maurillo L, et al. Targeting and depletion of acute myeloid leukemia blasts by MEN1112, a novel humanized defucosylated monoclonal antibodies with specificity for Bst1/CD157 antigen [abstract]. Blood. 2014;124(21):2235.
25. Aud D, Dusek R, Bisht A, et al. MEN1112, a novel humanized de-fucosylated monoclonal antibody with high affinity and specificity for Bst1/CD157 antigen and enhanced CD16 binding [abstract]. Blood. 2014;124(21):3606.
26. Jin L, Hope KJ, Zhai Q, Smadja-Joffe F, Dick JE. Targeting of CD44 eradicates human acute myeloid leukemic stem cells. Nat Med. 2006;12(10):1167–74.
27. 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. 2009;138(2):286–99.
28. Theocharides AP, Jin L, Cheng PY, et al. Disruption of SIRPalpha signaling in macrophages eliminates human acute myeloid leukemia stem cells in xenografts. J Exp Med. 2012;209(10):1883–99.
29. Kikushige Y, Shima T, Takayanagi S, et al. TIM-3 is a promising target to selectively kill acute myeloid leukemia stem cells. Cell Stem Cell. 2010;7(6):708–17.
30. Kuhne MR, Mulvey T, Belanger B, et al. BMS-936564/MDX-1338: a fully human anti-CXCR4 antibody induces apoptosis in vitro and shows antitumor activity in vivo in hematologic malignancies. Clin Cancer Res. 2013;19(2):357–66.
31. Pernasetti F, Liu S-H, Hallin M, et al. A novel CXCR4 antagonist IgG1 antibody (PF-06747143) for the treatment of hematological malignancies [abstract]. Blood. 2014;124(21):2311.
32. Becker PS, Foran JM, Altman JK, et al. Targeting the CXCR4 pathway: safety, tolerability and clinical activity of ulocuplumab (BMS-936564), an anti-CXCR4 antibody, in relapsed/refractory acute myeloid leukemia [abstract]. Blood. 2014;124(21):386.
33. Carter P. Improving the efficacy of antibody-based cancer therapies. Nat Rev Cancer. 2001;1(2):118–29. Excellent review article on antibody-based cancer therapies.
34. Riethmüller G. Symmetry breaking: bispecific antibodies, the beginnings, and 50 years on. Cancer Immun. 2012;12:12. Excellent review article on bispecific antibody constructs.
35. Baeuerle PA, Reinhardt C. Bispecific T-cell engaging antibodies for cancer therapy. Cancer Res. 2009;69(12):4941–4.
36. Topp MS, Gökbuget N, Zugmaier G, et al. Long-term follow-up of hematologic relapse-free survival in a phase 2 study of blinatumomab in patients with MRD in B-lineage ALL. Blood. 2012;120(26):5185–7.
37. Topp MS, Gökbuget N, Zugmaier G, et al. Phase II trial of the anti-CD19 bispecific T cell-engager blinatumomab shows hematologic and molecular remissions in patients with relapsed or refractory B-precursor acute lymphoblastic leukemia. J Clin Oncol. 2014;32(36):4134–40.
38. Topp MS, Gökbuget N, Stein AS, et al. Safety and activity of blinatumomab for adult patients with relapsed or refractory B-precursor acute lymphoblastic leukaemia: a multicentre, single-arm, phase 2 study. Lancet Oncol. 2015;16(1):57–66. Study on 189 adults with relapsed/refractory ALL, demonstrating the single agent activity of blinatumomab. This study forms the basis for regulatory approval of this drug in the U.S.
39. Lu H, Zhou Q, Deshmukh V, et al. Targeting human C-type lectin-like molecule-1 (CLL1) with a bispecific antibody for immunotherapy of acute myeloid leukemia. Angew Chem Int Ed Engl. 2014;53(37):9841–5.
40. 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. 2010;148(6):879–89.
41. Singer H, Kellner C, Lanig H, et al. Effective elimination of acute myeloid leukemic cells by recombinant bispecific antibody derivatives directed against CD33 and CD16. J Immunother. 2010;33(6):599–608.
42. Wiernik A, Foley B, Zhang B, et al. Targeting natural killer cells to acute myeloid leukemia in vitro with a CD16 × 33 bispecific killer cell engager and ADAM17 inhibition. Clin Cancer Res. 2013;19(14):3844–55.
43. Gleason MK, Ross JA, Warlick ED, et al. CD16×CD33 bispecific killer cell engager (BiKE) activates NK cells against primary MDS and MDSC CD33+ targets. Blood. 2014;123(19):3016–26.
44. Im J, Cernosek A, Sergeeva A, Molldrem JL, Sijie L. Novel TCR-like bi-specific T cell engaging antibody targeting the PR1/HLA-A2 myeloid leukemia antigen [abstract]. Blood. 2014;124(21):2314.
45. Stamova S, Cartellieri M, Feldmann A, et al. Unexpected recombinations in single chain bispecific anti-CD3-anti-CD33 antibodies can be avoided by a novel linker module. Mol Immunol. 2011;49(3):474–82.
46. Arndt C, von Bonin M, Cartellieri M, et al. Redirection of T cells with a first fully humanized bispecific CD33-CD3 antibody efficiently eliminates AML blasts without harming hematopoietic stem cells. Leukemia. 2013;27(4):964–7.
47. Aigner M, Feulner J, Schaffer S, et al. T lymphocytes can be effectively recruited for ex vivo and in vivo lysis of AML blasts by a novel CD33/CD3-bispecific BiTE antibody construct. Leukemia. 2013;27(5):1107–15.
48. Laszlo GS, Gudgeon CJ, Harrington KH, et al. Cellular determinants for preclinical activity of a novel CD33/CD3 bispecific T-cell engager (BiTE) antibody, AMG 330, against human AML. Blood. 2014;123(4):554–61.
49. Friedrich M, Henn A, Raum T, et al. Preclinical characterization of AMG 330, a CD3/CD33-bispecific T-cell-engaging antibody with potential for treatment of acute myelogenous leukemia. Mol Cancer Ther. 2014;13(6):1549–57.
50. Harrington KH, Gudgeon CJ, Laszlo GS, et al. The broad activity of the CD33/CD3 bispecific BiTE® antibody AMG 330 in primary human AML is impacted by disease stage and cytogenetic/molecular risk [abstract]. Blood. 2014;124(21):266.
51. Krupka C, Kufer P, Kischel R, et al. PD-1/PD-L1 blocking enhances CD33/CD3-bispecific BiTE® antibody (AMG 330) mediated lysis of primary AML cells [abstract]. Blood. 2014;124(21):3738.
52. Chu SY, Pong E, Chen H, et al. Immunotherapy with long-lived anti-CD123 × anti-CD3 bispecific antibodies stimulates potent T cell-mediated killing of human AML cell lines and of CD123+ cells in monkeys: a potential therapy for acute myelogenous leukemia [abstract]. Blood. 2014;124(21):2316.
53. Aliperta RA, Cartellieri M, Feldmann A, et al. Development of a bispecific antibody-releasing stem cell system for the eradication of acute myeloid leukemia blasts via redirected immune effector cells [abstract]. Blood. 2014;124(21):4810.
54. Arndt C, Feldmann A, von Bonin M, et al. Costimulation improves the killing capability of T cells redirected to tumor cells expressing low levels of CD33: description of a novel modular targeting system. Leukemia. 2014;28(1):59–69.
55. Kügler M, Stein C, Kellner C, et al. A recombinant trispecific single-chain Fv derivative directed against CD123 and CD33 mediates effective elimination of acute myeloid leukaemia cells by dual targeting. Br J Haematol. 2010;150(5):574–86.
56. Schubert I, Kellner C, Stein C, et al. A single-chain triplebody with specificity for CD19 and CD33 mediates effective lysis of mixed lineage leukemia cells by dual targeting. MAbs. 2011;3(1):21–30.
57. Stamova S, Cartellieri M, Feldmann A, et al. Simultaneous engagement of the activatory receptors NKG2D and CD3 for retargeting of effector cells to CD33-positive malignant cells. Leukemia. 2011;25(6):1053–6.
58. Cowan AJ, Laszlo GS, Estey EH, Walter RB. Antibody-based therapy of acute myeloid leukemia with gemtuzumab ozogamicin. Front Biosci (Landmark Ed). 2013;18(4):1311–34.
59. Amadori S, Suciu S, Selleslag D, et al. Improved overall survival with gemtuzumab ozogamicin (GO) compared with best supportive care (BSC) in elderly patients with untreated acute myeloid leukemia (AML) not considered fit for intensive chemotherapy: final results from the randomized phase III study (AML-19) of the EORTC and Gimema Leukemia Groups [abstract]. Blood. 2014;124(21):619.
60. Breccia M, Lo-Coco F. Gemtuzumab ozogamicin for the treatment of acute promyelocytic leukemia: mechanisms of action and resistance, safety and efficacy. Expert Opin Biol Ther. 2011;11(2):225–34.
61. 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. 2011;29(4):369–77. Randomized study showing benefit of GO in combination with induction chemotherapy in younger adults with AML.
62. 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. 2012;30(32):3924–31. Randomized study showing benefit of GO in combination with induction chemotherapy in older adults with AML.
63. 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. 2012;379(9825):1508–16. Randomized study showing benefit of GO in combination with induction chemotherapy in adults with AML.
64. Delaunay J, Recher C, Pigneux A, et al. Addition of gemtuzumab ozogamycin to chemotherapy improves event-free survival but not overall survival of AML patients with intermediate cytogenetics not eligible for allogeneic transplantation. Results of the GOELAMS AML 2006 IR study [abstract]. Blood. 2011;118(21):37–8.
65. Petersdorf SH, Kopecky KJ, Slovak M, et al. A phase 3 study of gemtuzumab ozogamicin during induction and postconsolidation therapy in younger patients with acute myeloid leukemia. Blood. 2013;121(24):4854–60.
66. Burnett AK, Hills RK, Hunter AE, et al. The addition of gemtuzumab ozogamicin to low-dose Ara-C improves remission rate but does not significantly prolong survival in older patients with acute myeloid leukaemia: results from the LRF AML14 and NCRI AML16 pick-a-winner comparison. Leukemia. 2013;27(1):75–81.
67. Löwenberg B, Beck J, Graux C, et al. Gemtuzumab ozogamicin as postremission treatment in AML at 60 years of age or more: results of a multicenter phase 3 study. Blood. 2010;115(13):2586–91.
68. Fernandez HF, Sun Z, Litzow MR, et al. Autologous transplantation gives encouraging results for young adults with favorable-risk acute myeloid leukemia, but is not improved with gemtuzumab ozogamicin. Blood. 2011;117(20):5306–13.
69. Hasle H, Abrahamsson J, Forestier E, et al. Gemtuzumab ozogamicin as postconsolidation therapy does not prevent relapse in children with AML: results from NOPHO-AML 2004. Blood. 2012;120(5):978–84.
70. Estey E. Treatment of AML: resurrection for gemtuzumab ozogamicin? Lancet. 2012;379(9825):1468–9.
71. Foran JM. Gemtuzumab: time to bring back on the market? Clin Adv Hematol Oncol. 2012;10(5):326–7.
72. Ravandi F, Estey EH, Appelbaum FR, et al. Gemtuzumab ozogamicin: time to resurrect? J Clin Oncol. 2012;30(32):3921–3.
73. Rowe JM, Löwenberg B. Gemtuzumab ozogamicin in acute myeloid leukemia: a remarkable saga about an active drug. Blood. 2013;121(24):4838–41.
74. Kharfan-Dabaja MA. A new dawn for gemtuzumab ozogamicin? Lancet Oncol. 2014;15(9):913–4.
75. Kung Sutherland MS, Walter RB, Jeffrey SC, et al. SGN-CD33A: a novel CD33-targeting antibody-drug conjugate using a pyrrolobenzodiazepine dimer is active in models of drug-resistant AML. Blood. 2013;122(8):1455–63.
76. Stein EM, Stein A, Walter RB, et al. Interim analysis of a phase 1 trial of SGN-CD33A in patients with CD33-positive acute myeloid leukemia (AML) [abstract]. Blood. 2014;124(21):623.
77. 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. 2012;30(3):1121–31.
78. Whiteman KR, Noordhuis P, Walker R, et al. The antibody-drug conjugate (ADC) IMGN779 is highly active in vitro and in vivo against acute myeloid leukemia (AML) with FLT3-ITD mutations [abstract]. Blood. 2014;124(21):2321.
79. Kreitman RJ. Immunotoxins in cancer therapy. Curr Opin Immunol. 1999;11(5):570–8.
80. Shapira A, Benhar I. Toxin-based therapeutic approaches. Toxins (Basel). 2010;2(11):2519–83.
81. Antignani A, Fitzgerald D. Immunotoxins: the role of the toxin. Toxins (Basel). 2013;5(8):1486–502.
82. Xu Y, Xu Q, Rosenblum MG, Scheinberg DA. Antileukemic activity of recombinant humanized M195-gelonin immunotoxin in nude mice. Leukemia. 1996;10(2):321–6.
83. Borthakur G, Rosenblum MG, Talpaz M, et al. Phase 1 study of an anti-CD33 immunotoxin, humanized monoclonal antibody M195 conjugated to recombinant gelonin (HUM-195/rGEL), in patients with advanced myeloid malignancies. Haematologica. 2013;98(2):217–21.
84. Frankel AE, Woo JH, Ahn C, et al. Activity of SL-401, a targeted therapy directed to interleukin-3 receptor, in blastic plasmacytoid dendritic cell neoplasm patients. Blood. 2014;124(3):385–92.
85. Frankel AE, Konopleva M, Hogge D, et al. Activity and tolerability of SL-401, a targeted therapy directed to the interleukin-3 receptor on cancer stem cells and tumor bulk, as a single agent in patients with advanced hematologic malignancies [abstract]. J Clin Oncol. 2013;31(Suppl):7029.
86. Testa U, Riccioni R, Biffoni M, et al. Diphtheria toxin fused to variant human interleukin-3 induces cytotoxicity of blasts from patients with acute myeloid leukemia according to the level of interleukin-3 receptor expression. Blood. 2005;106(7):2527–9.
87. Hogge DE, Yalcintepe L, Wong SH, Gerhard B, Frankel AE. Variant diphtheria toxin-interleukin-3 fusion proteins with increased receptor affinity have enhanced cytotoxicity against acute myeloid leukemia progenitors. Clin Cancer Res. 2006;12(4):1284–91.
88. Du X, Ho M, Pastan I. New immunotoxins targeting CD123, a stem cell antigen on acute myeloid leukemia cells. J Immunother. 2007;30(6):607–13.
89. Han L, Jorgensen JL, Wang SA, et al. Leukemia stem cell marker CD123 (IL-3R alpha) predicts minimal residual disease and relapse, providing a valid target for SL-101 in acute myeloid leukemia with FLT3-ITD mutations [abstract]. Blood. 2013;122(21):359.
90. Han L, Rowinsky E, Brooks C, et al. Anti-leukemia efficacy and mechanisms of action of SL-101, a novel anti-CD123 antibody-conjugate in acute myeloid leukemia [abstract]. Blood. 2014;124(21):981.
91. Zhong RK, van de Winkel JG, Thepen T, Schultz LD, Ball ED. Cytotoxicity of anti-CD64-ricin a chain immunotoxin against human acute myeloid leukemia cells in vitro and in SCID mice. J Hematother Stem Cell Res. 2001;10(1):95–105.
92. Tur MK, Huhn M, Jost E, Thepen T, Brummendorf TH, Barth S. In vivo efficacy of the recombinant anti-CD64 immunotoxin H22(scFv)-ETA' in a human acute myeloid leukemia xenograft tumor model. Int J Cancer. 2011;129(5):1277–82.
93. Stahnke B, Thepen T, Stocker M, et al. Granzyme B-H22(scFv), a human immunotoxin targeting CD64 in acute myeloid leukemia of monocytic subtypes. Mol Cancer Ther. 2008;7(9):2924–32.
94. Schiffer S, Letzian S, Jost E, et al. Granzyme M as a novel effector molecule for human cytolytic fusion proteins: CD64-specific cytotoxicity of Gm-H22(scFv) against leukemic cells. Cancer Lett. 2013;341(2):178–85.
95. Schiffer S, Rosinke R, Jost E, et al. Targeted ex vivo reduction of CD64-positive monocytes in chronic myelomonocytic leukemia and acute myelomonocytic leukemia using human granzyme B-based cytolytic fusion proteins. Int J Cancer. 2014;135(6):1497–508.
96. Walter RB, Pagel JM. Targeted radionuclide therapy for leukemia. In: Speer TW, editor. Targeted radionuclide therapy. 1st ed. Philadelphia: Lippincott Williams & Wilkins; 2011. p. 441–57.
97. Jurcic JG, Larson SM, Sgouros G, et al. Targeted alpha particle immunotherapy for myeloid leukemia. Blood. 2002;100(4):1233–9.
98. Mulford DA, Pandit-Taskar N, McDevitt MR, et al. Sequential therapy with cytarabine and bismuth-213 (213Bi)-labeled-HuM195 (anti-CD33) for acute myeloid leukemia (AML) [abstract]. Blood. 2004;104(11):496a.
99. Rosenblat TL, McDevitt MR, Pandit-Taskar N, et al. Phase I trial of the targeted alpha-particle nano-generator actinium-225 (225Ac)-HuM195 (anti-CD33) in acute myeloid leukemia (AML) [abstract]. Blood. 2007;110(11):277a.
100. Rosenblat TL, McDevitt MR, Mulford DA, et al. Sequential cytarabine and alpha-particle immunotherapy with bismuth-213-lintuzumab (HuM195) for acute myeloid leukemia. Clin Cancer Res. 2010;16(21):5303–11.
101. Jurcic JG, Ravandi F, Pagel JM, et al. Phase I trial of the targeted alpha-particle nano-generator actinium-225 (225Ac)-lintuzumab (anti-CD33) in combination with low-dose cytarabine (LDAC) for older patients with untreated acute myeloid leukemia (AML) [abstract]. Blood. 2013;122(21):1460.
102. Fry TJ, Mackall CL. T-cell adoptive immunotherapy for acute lymphoblastic leukemia. Hematol Am Soc Hematol Educ Program. 2013;2013:348–53.
103. Lee DW, Kochenderfer JN, Stetler-Stevenson M, et al. T cells expressing CD19 chimeric antigen receptors for acute lymphoblastic leukaemia in children and young adults: a phase 1 dose-escalation trial. Lancet. 2015;385(9967):517–28. Relatively small study demonstrating the exquisit activity of CD19-directed CAR T-cells in ALL.
104. Maude SL, Frey N, Shaw PA, et al. Chimeric antigen receptor T cells for sustained remissions in leukemia. N Engl J Med. 2014;371(16):1507–17. Relatively small study demonstrating the exquisit activity of CD19-directed CAR T-cells in ALL.
105. Marin V, Pizzitola I, Agostoni V, et al. Cytokine-induced killer cells for cell therapy of acute myeloid leukemia: improvement of their immune activity by expression of CD33-specific chimeric receptors. Haematologica. 2010;95(12):2144–52.
106. Dutour A, Marin V, Pizzitola I, et al. In vitro and in vivo antitumor effect of anti-CD33 chimeric receptor-expressing EBV-CTL against CD33+ acute myeloid leukemia. Adv Hematol. 2012;2012:683065.
107. Tettamanti S, Marin V, Pizzitola I, et al. Targeting of acute myeloid leukaemia by cytokine-induced killer cells redirected with a novel CD123-specific chimeric antigen receptor. Br J Haematol. 2013;161(3):389–401.
108. Mardiros A, Dos Santos C, McDonald T, et al. T cells expressing CD123-specific chimeric antigen receptors exhibit specific cytolytic effector functions and antitumor effects against human acute myeloid leukemia. Blood. 2013;122(18):3138–48.
109. Pizzitola I, Anjos-Afonso F, Rouault-Pierre K, et al. Chimeric antigen receptors against CD33/CD123 antigens efficiently target primary acute myeloid leukemia cells in vivo. Leukemia. 2014;28(8):1596–605.
110. Gill S, Tasian SK, Ruella M, et al. Preclinical targeting of human acute myeloid leukemia and myeloablation using chimeric antigen receptor-modified T cells. Blood. 2014;123(15):2343–54.
111. O' Hear C, Heiber JF, Schubert I, Fey G, Geiger TL. Anti-CD33 chimeric antigen receptor targeting of acute myeloid leukemia. Haematologica. 2015;100(3):336–44.
112. Rafiq S, Dao T, Liu C, Scheinberg DA, Brentjens RJ. Engineered T cell receptor-mimic antibody, (TCRm) chimeric antigen receptor (CAR) T cells against the intracellular protein Wilms tumor-1 (WT1) for treatment of hematologic and solid cancers [abstract]. Blood. 2014;124(21):2155.
113. Westwood JA, Smyth MJ, Teng MW, et al. Adoptive transfer of T cells modified with a humanized chimeric receptor gene inhibits growth of Lewis-Y-expressing tumors in mice. Proc Natl Acad Sci U S A. 2005;102(52):19051–6.
114. Ritchie DS, Neeson PJ, Khot A, et al. Persistence and efficacy of second generation CAR T cell against the LeY antigen in acute myeloid leukemia. Mol Ther. 2013;21(11):2122–9.
115. Bar M, Chapuis AG, Schmitt TM, et al. Transferred donor-derived virus specific CD8+ T cells that have been transduced to express a WT1-specific T cell receptor can persist and provide anti-leukemic activity in AML patients post-transplant [abstract]. Blood. 2014;124(21):3939.
116. Martner A, Thorén FB, Aurelius J, Hellstrand K. Immunotherapeutic strategies for relapse control in acute myeloid leukemia. Blood Rev. 2013;27(5):209–16.
117. 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(6):1924–32.
118. Greiner J, Schneider V, Schmitt M, et al. Immune responses against the mutated region of cytoplasmatic NPM1 might contribute to the favorable clinical outcome of AML patients with NPM1 mutations (NPM1mut). Blood. 2013;122(6):1087–8.
119. Rein LA, Chao NJ. WT1 vaccination in acute myeloid leukemia: new methods of implementing adoptive immunotherapy. Expert Opin Investig Drugs. 2014;23(3):417–26.
120. Qazilbash MH, Wieder ED, Thall PF, et al. PR1 peptide vaccine-induced immune response is associated with better event-free survival in patients with myeloid leukemia [abstract]. Blood. 2007;110(11):90a.
121. Schmitt M, Schmitt A, Rojewski MT, et al. RHAMM-R3 peptide vaccination in patients with acute myeloid leukemia, myelodysplastic syndrome, and multiple myeloma elicits immunologic and clinical responses. Blood. 2008;111(3):1357–65.
122. Greiner J, Schmitt A, Giannopoulos K, et al. High-dose RHAMM-R3 peptide vaccination for patients with acute myeloid leukemia, myelodysplastic syndrome and multiple myeloma. Haematologica. 2010;95(7):1191–7.
123. 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(1):236–42.
124. 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. 2011;96(3):432–40.
125. 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. 2004;19(2):66–70.
126. 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. 2006;28(4):855–61.
127. 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. 2006;133(2):152–7.
128. 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 U S A. 2010;107(31):13824–9.
129. Berneman ZN, Van de Velde A, Anguille S, et al. Prevention of relapse in acute myeloid leukemia by dendritic cell vaccination: report on a phase II study with 29 patients [abstract]. Blood. 2013;122(21):236.
130. Rosenblatt J, Stone RM, Uhl L, et al. Clinical trial evaluating DC/AML fusion cell vaccination in AML patients [abstract]. Blood. 2013;122(21):3928.
131. van de Loosdrecht AA, van Wetering S, Santegoeds S, et al. Clinical and immunological results of a phase I/IIa study of allogeneic dendritic cell (DC) vaccination, an “off the shelf” treatment to prevent or delay relapse in elderly patients with acute myeloid leukemia [abstract]. Blood. 2013;122(21):2651.