Skip to main content
Erschienen in: Annals of Hematology 12/2017

28.10.2017 | Review Article

The progress and current status of immunotherapy in acute myeloid leukemia

verfasst von: Dan Yang, Xiuqun Zhang, Xuezhong Zhang, Yanli Xu

Erschienen in: Annals of Hematology | Ausgabe 12/2017

Einloggen, um Zugang zu erhalten

Abstract

Recently, there has been remarkable progress in basic and preclinical studies of acute myeloid leukemia (AML). The improved outcomes of AML can largely be attributed to advances in supportive care and hematopoietic cell transplantation as opposed to conventional chemotherapy. However, as the 5-year survival rate remains low due to a high incidence of relapse, novel and effective treatments are urgently needed. Increasing attention is focusing on identifying suitable immunotherapeutic strategies for AML. Here, we describe the immunological features, mechanisms of immune escape, and recent progress in immunotherapy for AML. Problems encountered in the clinic will also be discussed. Although current outcomes may be limited, ongoing preclinical or clinical efforts are aimed at improving immunotherapy modalities and designing novel therapies, such as vaccines, monoclonal antibody therapy, chimeric antibody receptor-engineered T cells (CAR-T), TCR-engineered T cells (TCR-T), and checkpoint inhibitors, which may provide promising and effective therapies with higher specificity and efficacy for AML.
Literatur
2.
Zurück zum Zitat Pleyer L, Stauder R, Burgstaller S, Schreder M, Tinchon C, Pfeilstocker M, Steinkirchner S, Melchardt T, Mitrovic M, Girschikofsky M, Lang A, Krippl P, Sliwa T, Egle A, Linkesch W, Voskova D, Angermann H, Greil R (2013) Azacitidine in patients with WHO-defined AML—results of 155 patients from the Austrian Azacitidine Registry of the AGMT-Study Group. J Hematol Oncol 6:32. https://doi.org/10.1186/1756-8722-6-32 PubMedPubMedCentralCrossRef Pleyer L, Stauder R, Burgstaller S, Schreder M, Tinchon C, Pfeilstocker M, Steinkirchner S, Melchardt T, Mitrovic M, Girschikofsky M, Lang A, Krippl P, Sliwa T, Egle A, Linkesch W, Voskova D, Angermann H, Greil R (2013) Azacitidine in patients with WHO-defined AML—results of 155 patients from the Austrian Azacitidine Registry of the AGMT-Study Group. J Hematol Oncol 6:32. https://​doi.​org/​10.​1186/​1756-8722-6-32 PubMedPubMedCentralCrossRef
3.
Zurück zum Zitat Yates JW, Wallace HJ Jr, Ellison RR, Holland JF (1973) Cytosine arabinoside (NSC-63878) and daunorubicin (NSC-83142) therapy in acute nonlymphocytic leukemia. Cancer Chemother Rep 57(4):485–488PubMed Yates JW, Wallace HJ Jr, Ellison RR, Holland JF (1973) Cytosine arabinoside (NSC-63878) and daunorubicin (NSC-83142) therapy in acute nonlymphocytic leukemia. Cancer Chemother Rep 57(4):485–488PubMed
5.
Zurück zum Zitat Whiteway A, Corbett T, Anderson R, Macdonald I, Prentice HG (2003) Expression of co-stimulatory molecules on acute myeloid leukaemia blasts may effect duration of first remission. Br J Haematol 120(3):442–451PubMedCrossRef Whiteway A, Corbett T, Anderson R, Macdonald I, Prentice HG (2003) Expression of co-stimulatory molecules on acute myeloid leukaemia blasts may effect duration of first remission. Br J Haematol 120(3):442–451PubMedCrossRef
12.
Zurück zum Zitat Steinbacher J, Schmiedel BJ, Werner A, Nuebling T, Buechele C, Grosse-Hovest L, Kanz L, Salih HR (2012) Bimodal induction of NK cell reactivity against acute myeloid (AML) and chronic lymphoid leukemia (CLL) by Fc-engineered GITR-Fc fusion proteins [abstract]. Blood 120(21):2143 Steinbacher J, Schmiedel BJ, Werner A, Nuebling T, Buechele C, Grosse-Hovest L, Kanz L, Salih HR (2012) Bimodal induction of NK cell reactivity against acute myeloid (AML) and chronic lymphoid leukemia (CLL) by Fc-engineered GITR-Fc fusion proteins [abstract]. Blood 120(21):2143
13.
Zurück zum Zitat Yang H, Bueso-Ramos C, DiNardo C, Estecio MR, Davanlou M, Geng QR, Fang Z, Nguyen M, Pierce S, Wei Y, Parmar S, Cortes J, Kantarjian H, Garcia-Manero G (2014) Expression of PD-L1, PD-L2, PD-1 and CTLA4 in myelodysplastic syndromes is enhanced by treatment with hypomethylating agents. Leukemia 28(6):1280–1288. https://doi.org/10.1038/leu.2013.355 PubMedCrossRef Yang H, Bueso-Ramos C, DiNardo C, Estecio MR, Davanlou M, Geng QR, Fang Z, Nguyen M, Pierce S, Wei Y, Parmar S, Cortes J, Kantarjian H, Garcia-Manero G (2014) Expression of PD-L1, PD-L2, PD-1 and CTLA4 in myelodysplastic syndromes is enhanced by treatment with hypomethylating agents. Leukemia 28(6):1280–1288. https://​doi.​org/​10.​1038/​leu.​2013.​355 PubMedCrossRef
14.
Zurück zum Zitat Salih HR, Schmetzer HM, Burke C, Starling GC, Dunn R, Pelka-Fleischer R, Nuessler V, Kiener PA (2001) Soluble CD137 (4-1BB) ligand is released following leukocyte activation and is found in sera of patients with hematological malignancies. J Immunol 167(7):4059–4066PubMedCrossRef Salih HR, Schmetzer HM, Burke C, Starling GC, Dunn R, Pelka-Fleischer R, Nuessler V, Kiener PA (2001) Soluble CD137 (4-1BB) ligand is released following leukocyte activation and is found in sera of patients with hematological malignancies. J Immunol 167(7):4059–4066PubMedCrossRef
18.
Zurück zum Zitat Buggins AG, Milojkovic D, Arno MJ, Lea NC, Mufti GJ, Thomas NS, Hirst WJ (2001) Microenvironment produced by acute myeloid leukemia cells prevents T cell activation and proliferation by inhibition of NF-kappaB, c-Myc, and pRb pathways. J Immunol 167(10):6021–6030PubMedCrossRef Buggins AG, Milojkovic D, Arno MJ, Lea NC, Mufti GJ, Thomas NS, Hirst WJ (2001) Microenvironment produced by acute myeloid leukemia cells prevents T cell activation and proliferation by inhibition of NF-kappaB, c-Myc, and pRb pathways. J Immunol 167(10):6021–6030PubMedCrossRef
24.
Zurück zum Zitat Powles RL, Balchin LA, Fairley GH, Alexander P (1971) Recognition of leukaemia cells as foreign before and after autoimmunization. Br Med J 1(5747):486–489PubMedPubMedCentralCrossRef Powles RL, Balchin LA, Fairley GH, Alexander P (1971) Recognition of leukaemia cells as foreign before and after autoimmunization. Br Med J 1(5747):486–489PubMedPubMedCentralCrossRef
25.
Zurück zum Zitat Van Tendeloo VF, Van Broeckhoven C, Berneman ZN (2001) Gene-based cancer vaccines: an ex vivo approach. Leukemia 15(4):545–558PubMedCrossRef Van Tendeloo VF, Van Broeckhoven C, Berneman ZN (2001) Gene-based cancer vaccines: an ex vivo approach. Leukemia 15(4):545–558PubMedCrossRef
27.
28.
Zurück zum Zitat Greiner J, Dohner H, Schmitt M (2006) Cancer vaccines for patients with acute myeloid leukemia—definition of leukemia-associated antigens and current clinical protocols targeting these antigens. Haematologica 91(12):1653–1661PubMed Greiner J, Dohner H, Schmitt M (2006) Cancer vaccines for patients with acute myeloid leukemia—definition of leukemia-associated antigens and current clinical protocols targeting these antigens. Haematologica 91(12):1653–1661PubMed
29.
Zurück zum Zitat Kwon M, Martinez-Laperche C, Infante M, Carretero F, Balsalobre P, Serrano D, Gayoso J, Perez-Corral A, Anguita J, Diez-Martin JL, Buno I (2012) Evaluation of minimal residual disease by real-time quantitative PCR of Wilms’ tumor 1 expression in patients with acute myelogenous leukemia after allogeneic stem cell transplantation: correlation with flow cytometry and chimerism. Biol Blood Marrow Transplant 18(8):1235–1242. https://doi.org/10.1016/j.bbmt.2012.01.012 PubMedCrossRef Kwon M, Martinez-Laperche C, Infante M, Carretero F, Balsalobre P, Serrano D, Gayoso J, Perez-Corral A, Anguita J, Diez-Martin JL, Buno I (2012) Evaluation of minimal residual disease by real-time quantitative PCR of Wilms’ tumor 1 expression in patients with acute myelogenous leukemia after allogeneic stem cell transplantation: correlation with flow cytometry and chimerism. Biol Blood Marrow Transplant 18(8):1235–1242. https://​doi.​org/​10.​1016/​j.​bbmt.​2012.​01.​012 PubMedCrossRef
30.
31.
Zurück zum Zitat Liu H, Zha Y, Malnassy G, Fulton N, Green M, Park J-H, Nakamura Y, Larson RA, Salazar AM, Odenike O, Gajewski T, Stock W (2016) WT1 peptide vaccine is able to induce WT1-specifc immune response with TCR clonal enrichment to control minimal residual disease in patients with myeloid leukemia [abstract]. Blood 128(22):3984 Liu H, Zha Y, Malnassy G, Fulton N, Green M, Park J-H, Nakamura Y, Larson RA, Salazar AM, Odenike O, Gajewski T, Stock W (2016) WT1 peptide vaccine is able to induce WT1-specifc immune response with TCR clonal enrichment to control minimal residual disease in patients with myeloid leukemia [abstract]. Blood 128(22):3984
32.
Zurück zum Zitat Molldrem J, Dermime S, Parker K, Jiang YZ, Mavroudis D, Hensel N, Fukushima P, Barrett AJ (1996) Targeted T-cell therapy for human leukemia: cytotoxic T lymphocytes specific for a peptide derived from proteinase 3 preferentially lyse human myeloid leukemia cells. Blood 88(7):2450–2457PubMed Molldrem J, Dermime S, Parker K, Jiang YZ, Mavroudis D, Hensel N, Fukushima P, Barrett AJ (1996) Targeted T-cell therapy for human leukemia: cytotoxic T lymphocytes specific for a peptide derived from proteinase 3 preferentially lyse human myeloid leukemia cells. Blood 88(7):2450–2457PubMed
35.
Zurück zum Zitat Ma Q, Garber HR, Lu S, He H, Tallis E, Ding X, Sergeeva A, Wood MS, Dotti G, Salvado B, Ruisaard K, Clise-Dwyer K, John LS, Rezvani K, Alatrash G, Shpall EJ, Molldrem JJ (2016) A novel TCR-like CAR with specificity for PR1/HLA-A2 effectively targets myeloid leukemia in vitro when expressed in human adult peripheral blood and cord blood T cells. Cytotherapy 18(8):985–994. https://doi.org/10.1016/j.jcyt.2016.05.001 PubMedPubMedCentralCrossRef Ma Q, Garber HR, Lu S, He H, Tallis E, Ding X, Sergeeva A, Wood MS, Dotti G, Salvado B, Ruisaard K, Clise-Dwyer K, John LS, Rezvani K, Alatrash G, Shpall EJ, Molldrem JJ (2016) A novel TCR-like CAR with specificity for PR1/HLA-A2 effectively targets myeloid leukemia in vitro when expressed in human adult peripheral blood and cord blood T cells. Cytotherapy 18(8):985–994. https://​doi.​org/​10.​1016/​j.​jcyt.​2016.​05.​001 PubMedPubMedCentralCrossRef
36.
Zurück zum Zitat Qazilbash MH, Wieder E, Thall PF, Wang X, Rios R, Lu S, Kanodia S, Ruisaard KE, Giralt SA, Estey EH, Cortes J, Komanduri KV, Clise-Dwyer K, Alatrash G, Ma Q, Champlin RE, Molldrem JJ (2017) PR1 peptide vaccine induces specific immunity with clinical responses in myeloid malignancies. Leukemia 31(3):697–704. https://doi.org/10.1038/leu.2016.254 PubMedCrossRef Qazilbash MH, Wieder E, Thall PF, Wang X, Rios R, Lu S, Kanodia S, Ruisaard KE, Giralt SA, Estey EH, Cortes J, Komanduri KV, Clise-Dwyer K, Alatrash G, Ma Q, Champlin RE, Molldrem JJ (2017) PR1 peptide vaccine induces specific immunity with clinical responses in myeloid malignancies. Leukemia 31(3):697–704. https://​doi.​org/​10.​1038/​leu.​2016.​254 PubMedCrossRef
39.
Zurück zum Zitat Sherman L, Sleeman J, Herrlich P, Ponta H (1994) Hyaluronate receptors: key players in growth, differentiation, migration and tumor progression. Curr Opin Cell Biol 6(5):726–733PubMedCrossRef Sherman L, Sleeman J, Herrlich P, Ponta H (1994) Hyaluronate receptors: key players in growth, differentiation, migration and tumor progression. Curr Opin Cell Biol 6(5):726–733PubMedCrossRef
40.
41.
Zurück zum Zitat Schmitt M, Schmitt A, Rojewski MT, Chen J, Giannopoulos K, Fei F, Yu Y, Gotz M, Heyduk M, Ritter G, Speiser DE, Gnjatic S, Guillaume P, Ringhoffer M, Schlenk RF, Liebisch P, Bunjes D, Shiku H, Dohner H, Greiner J (2008) RHAMM-R3 peptide vaccination in patients with acute myeloid leukemia, myelodysplastic syndrome, and multiple myeloma elicits immunologic and clinical responses. Blood 111(3):1357–1365. https://doi.org/10.1182/blood-2007-07-099366 PubMedCrossRef Schmitt M, Schmitt A, Rojewski MT, Chen J, Giannopoulos K, Fei F, Yu Y, Gotz M, Heyduk M, Ritter G, Speiser DE, Gnjatic S, Guillaume P, Ringhoffer M, Schlenk RF, Liebisch P, Bunjes D, Shiku H, Dohner H, Greiner J (2008) RHAMM-R3 peptide vaccination in patients with acute myeloid leukemia, myelodysplastic syndrome, and multiple myeloma elicits immunologic and clinical responses. Blood 111(3):1357–1365. https://​doi.​org/​10.​1182/​blood-2007-07-099366 PubMedCrossRef
48.
Zurück zum Zitat Van Tendeloo VF, Van de Velde A, Van Driessche A, Cools N, Anguille S, Ladell K, Gostick E, Vermeulen K, Pieters K, Nijs G, Stein B, Smits EL, Schroyens WA, Gadisseur AP, Vrelust I, Jorens PG, Goossens H, de Vries IJ, Price DA, Oji Y, Oka Y, Sugiyama H, Berneman ZN (2010) 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 107(31):13824–13829. https://doi.org/10.1073/pnas.1008051107 PubMedPubMedCentralCrossRef Van Tendeloo VF, Van de Velde A, Van Driessche A, Cools N, Anguille S, Ladell K, Gostick E, Vermeulen K, Pieters K, Nijs G, Stein B, Smits EL, Schroyens WA, Gadisseur AP, Vrelust I, Jorens PG, Goossens H, de Vries IJ, Price DA, Oji Y, Oka Y, Sugiyama H, Berneman ZN (2010) 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 107(31):13824–13829. https://​doi.​org/​10.​1073/​pnas.​1008051107 PubMedPubMedCentralCrossRef
49.
Zurück zum Zitat Berneman ZN, Velde ALVd, Willemen Y, Anguille S, Saevels K, Germonpré P, Huizing MT, Peeters M, Snoeckx A, Parizel P, Tendeloo VFV, Lion E, Nijs G, Stein B, Vermeulen K, Maes M-B, Malfait R, Vrelust I, Verlinden A, Gadisseur AP, Schroyens WA, Lammens M, Smits EL (2014) Vaccination with WT1 mRNA-electroporated dendritic cells: report of clinical outcome in 66 cancer patients [abstract]. Blood 124(21):310 Berneman ZN, Velde ALVd, Willemen Y, Anguille S, Saevels K, Germonpré P, Huizing MT, Peeters M, Snoeckx A, Parizel P, Tendeloo VFV, Lion E, Nijs G, Stein B, Vermeulen K, Maes M-B, Malfait R, Vrelust I, Verlinden A, Gadisseur AP, Schroyens WA, Lammens M, Smits EL (2014) Vaccination with WT1 mRNA-electroporated dendritic cells: report of clinical outcome in 66 cancer patients [abstract]. Blood 124(21):310
50.
Zurück zum Zitat Padua RA, Larghero J, Robin M, le Pogam C, Schlageter MH, Muszlak S, Fric J, West R, Rousselot P, Phan TH, Mudde L, Teisserenc H, Carpentier AF, Kogan S, Degos L, Pla M, Bishop JM, Stevenson F, Charron D, Chomienne C (2003) PML-RARA-targeted DNA vaccine induces protective immunity in a mouse model of leukemia. Nat Med 9(11):1413–1417. https://doi.org/10.1038/nm949 PubMedCrossRef Padua RA, Larghero J, Robin M, le Pogam C, Schlageter MH, Muszlak S, Fric J, West R, Rousselot P, Phan TH, Mudde L, Teisserenc H, Carpentier AF, Kogan S, Degos L, Pla M, Bishop JM, Stevenson F, Charron D, Chomienne C (2003) PML-RARA-targeted DNA vaccine induces protective immunity in a mouse model of leukemia. Nat Med 9(11):1413–1417. https://​doi.​org/​10.​1038/​nm949 PubMedCrossRef
52.
Zurück zum Zitat Timmerman JM, Singh G, Hermanson G, Hobart P, Czerwinski DK, Taidi B, Rajapaksa R, Caspar CB, Van Beckhoven A, Levy R (2002) Immunogenicity of a plasmid DNA vaccine encoding chimeric idiotype in patients with B-cell lymphoma. Cancer Res 62(20):5845–5852PubMed Timmerman JM, Singh G, Hermanson G, Hobart P, Czerwinski DK, Taidi B, Rajapaksa R, Caspar CB, Van Beckhoven A, Levy R (2002) Immunogenicity of a plasmid DNA vaccine encoding chimeric idiotype in patients with B-cell lymphoma. Cancer Res 62(20):5845–5852PubMed
54.
Zurück zum Zitat Kohler G, Milstein C (2005) Continuous cultures of fused cells secreting antibody of predefined specificity. 1975. J Immunol 174(5):2453–2455PubMed Kohler G, Milstein C (2005) Continuous cultures of fused cells secreting antibody of predefined specificity. 1975. J Immunol 174(5):2453–2455PubMed
55.
Zurück zum Zitat Cowan AJ, Laszlo GS, Estey EH, Walter RB (2013) Antibody-based therapy of acute myeloid leukemia with gemtuzumab ozogamicin. Front Biosci (Landmark Ed) 18:1311–1334CrossRef Cowan AJ, Laszlo GS, Estey EH, Walter RB (2013) Antibody-based therapy of acute myeloid leukemia with gemtuzumab ozogamicin. Front Biosci (Landmark Ed) 18:1311–1334CrossRef
56.
57.
Zurück zum Zitat Caron PC, Dumont L, Scheinberg DA (1998) Supersaturating infusional humanized anti-CD33 monoclonal antibody HuM195 in myelogenous leukemia. Clin Cancer Res 4(6):1421–1428PubMed Caron PC, Dumont L, Scheinberg DA (1998) Supersaturating infusional humanized anti-CD33 monoclonal antibody HuM195 in myelogenous leukemia. Clin Cancer Res 4(6):1421–1428PubMed
59.
Zurück zum Zitat Damle NK, Frost P (2003) Antibody-targeted chemotherapy with immunoconjugates of calicheamicin. Curr Opin Pharmacol 3(4):386–390PubMedCrossRef Damle NK, Frost P (2003) Antibody-targeted chemotherapy with immunoconjugates of calicheamicin. Curr Opin Pharmacol 3(4):386–390PubMedCrossRef
60.
63.
Zurück zum Zitat Amadori S, Suciu S, Selleslag D, Aversa F, Gaidano G, Musso M, Annino L, Venditti A, Voso MT, Mazzone C, Magro D, De Fabritiis P, Muus P, Alimena G, Mancini M, Hagemeijer A, Paoloni F, Vignetti M, Fazi P, Meert L, Ramadan SM, Willemze R, de Witte T, Baron F (2016) Gemtuzumab ozogamicin versus best supportive care in older patients with newly diagnosed acute myeloid leukemia unsuitable for intensive chemotherapy: results of the randomized phase III EORTC-GIMEMA AML-19 trial. J Clin Oncol 34(9):972–979. https://doi.org/10.1200/jco.2015.64.0060 PubMedCrossRef Amadori S, Suciu S, Selleslag D, Aversa F, Gaidano G, Musso M, Annino L, Venditti A, Voso MT, Mazzone C, Magro D, De Fabritiis P, Muus P, Alimena G, Mancini M, Hagemeijer A, Paoloni F, Vignetti M, Fazi P, Meert L, Ramadan SM, Willemze R, de Witte T, Baron F (2016) Gemtuzumab ozogamicin versus best supportive care in older patients with newly diagnosed acute myeloid leukemia unsuitable for intensive chemotherapy: results of the randomized phase III EORTC-GIMEMA AML-19 trial. J Clin Oncol 34(9):972–979. https://​doi.​org/​10.​1200/​jco.​2015.​64.​0060 PubMedCrossRef
64.
Zurück zum Zitat Kung Sutherland MS, Walter RB, Jeffrey SC, Burke PJ, Yu C, Kostner H, Stone I, Ryan MC, Sussman D, Lyon RP, Zeng W, Harrington KH, Klussman K, Westendorf L, Meyer D, Bernstein ID, Senter PD, Benjamin DR, Drachman JG, McEarchern JA (2013) SGN-CD33A: a novel CD33-targeting antibody-drug conjugate using a pyrrolobenzodiazepine dimer is active in models of drug-resistant AML. Blood 122(8):1455–1463. https://doi.org/10.1182/blood-2013-03-491506 PubMedCrossRef Kung Sutherland MS, Walter RB, Jeffrey SC, Burke PJ, Yu C, Kostner H, Stone I, Ryan MC, Sussman D, Lyon RP, Zeng W, Harrington KH, Klussman K, Westendorf L, Meyer D, Bernstein ID, Senter PD, Benjamin DR, Drachman JG, McEarchern JA (2013) SGN-CD33A: a novel CD33-targeting antibody-drug conjugate using a pyrrolobenzodiazepine dimer is active in models of drug-resistant AML. Blood 122(8):1455–1463. https://​doi.​org/​10.​1182/​blood-2013-03-491506 PubMedCrossRef
65.
Zurück zum Zitat Stein EM (2014) Interim analysis of a phase 1 trial of SGN-CD33A in patients with CD33-positive acute myeloid leukemia (AML). Blood Abstract 124:623 Stein EM (2014) Interim analysis of a phase 1 trial of SGN-CD33A in patients with CD33-positive acute myeloid leukemia (AML). Blood Abstract 124:623
66.
Zurück zum Zitat Krystal WM, Walker R, Fishkin N, Audette C, Kovtun Y, Romanelli A (2015) IMGN779, a CD33-targeted antibody-drug conjugate (ADC) with a novel DNA-alkylating effector molecule, induces DNA damage, cell cycle arrest, and apoptosis in AML cells [abstract]. Blood 126(23):1366 Krystal WM, Walker R, Fishkin N, Audette C, Kovtun Y, Romanelli A (2015) IMGN779, a CD33-targeted antibody-drug conjugate (ADC) with a novel DNA-alkylating effector molecule, induces DNA damage, cell cycle arrest, and apoptosis in AML cells [abstract]. Blood 126(23):1366
67.
Zurück zum Zitat Portwood S, Puchalski RA, Walker RM, Wang ES (2016) Combining IMGN779, a novel anti-CD33 antibody-drug conjugate (ADC), with the PARP inhibitor, olaparib, results in enhanced anti-tumor activity in preclinical acute myeloid leukemia (AML) models [abstract]. Blood 128(22):1645 Portwood S, Puchalski RA, Walker RM, Wang ES (2016) Combining IMGN779, a novel anti-CD33 antibody-drug conjugate (ADC), with the PARP inhibitor, olaparib, results in enhanced anti-tumor activity in preclinical acute myeloid leukemia (AML) models [abstract]. Blood 128(22):1645
69.
Zurück zum Zitat Munoz L, Nomdedeu JF, Lopez O, Carnicer MJ, Bellido M, Aventin A, Brunet S, Sierra J (2001) Interleukin-3 receptor alpha chain (CD123) is widely expressed in hematologic malignancies. Haematologica 86(12):1261–1269PubMed Munoz L, Nomdedeu JF, Lopez O, Carnicer MJ, Bellido M, Aventin A, Brunet S, Sierra J (2001) Interleukin-3 receptor alpha chain (CD123) is widely expressed in hematologic malignancies. Haematologica 86(12):1261–1269PubMed
70.
Zurück zum Zitat Testa U, Riccioni R, Militi S, Coccia E, Stellacci E, Samoggia P, Latagliata R, Mariani G, Rossini A, Battistini A, Lo-Coco F, Peschle C (2002) Elevated expression of IL-3Ralpha in acute myelogenous leukemia is associated with enhanced blast proliferation, increased cellularity, and poor prognosis. Blood 100(8):2980–2988. https://doi.org/10.1182/blood-2002-03-0852 PubMedCrossRef Testa U, Riccioni R, Militi S, Coccia E, Stellacci E, Samoggia P, Latagliata R, Mariani G, Rossini A, Battistini A, Lo-Coco F, Peschle C (2002) Elevated expression of IL-3Ralpha in acute myelogenous leukemia is associated with enhanced blast proliferation, increased cellularity, and poor prognosis. Blood 100(8):2980–2988. https://​doi.​org/​10.​1182/​blood-2002-03-0852 PubMedCrossRef
71.
Zurück zum Zitat He SZ, Busfield S, Ritchie DS, Hertzberg MS, Durrant S, Lewis ID, Marlton P, McLachlan AJ, Kerridge I, Bradstock KF, Kennedy G, Boyd AW, Yeadon TM, Lopez AF, Ramshaw HS, Iland H, Bamford S, Barnden M, DeWitte M, Basser R, Roberts AW (2015) 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 56(5):1406–1415. https://doi.org/10.3109/10428194.2014.956316 PubMedCrossRef He SZ, Busfield S, Ritchie DS, Hertzberg MS, Durrant S, Lewis ID, Marlton P, McLachlan AJ, Kerridge I, Bradstock KF, Kennedy G, Boyd AW, Yeadon TM, Lopez AF, Ramshaw HS, Iland H, Bamford S, Barnden M, DeWitte M, Basser R, Roberts AW (2015) 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 56(5):1406–1415. https://​doi.​org/​10.​3109/​10428194.​2014.​956316 PubMedCrossRef
72.
Zurück zum Zitat Smith BD, Roboz GJ, Walter RB, Altman JK, Ferguson A, Curcio TJ, Orlowski KF, Garrett L, Busfield SJ, Barnden M, Sedgmen B, Ghosh S, Hosback S, Davis R, Dyson A, Dasen S, DeWitte M, Bensen-Kennedy DM, Roberts AW (2014) 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 124(21):120 Smith BD, Roboz GJ, Walter RB, Altman JK, Ferguson A, Curcio TJ, Orlowski KF, Garrett L, Busfield SJ, Barnden M, Sedgmen B, Ghosh S, Hosback S, Davis R, Dyson A, Dasen S, DeWitte M, Bensen-Kennedy DM, Roberts AW (2014) 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 124(21):120
73.
Zurück zum Zitat Sweet KL, Pemmaraju N, Lane AA, Stein AS, Vasu S, Blum W, Rizzieri DA, Wang ES, Rowinsky EK, Szarek M, Brooks CL, Disalvatore S, Liu D, Duvic M, Schwartz JD, Konopleva M (2015) Lead-in stage results of a pivotal trial of SL-401, an interleukin-3 receptor (IL-3R) targeting biologic, in patients with blastic plasmacytoid dendritic cell neoplasm (BPDCN) or acute myeloid leukemia (AML) [abstract]. Blood 126(23):3795 Sweet KL, Pemmaraju N, Lane AA, Stein AS, Vasu S, Blum W, Rizzieri DA, Wang ES, Rowinsky EK, Szarek M, Brooks CL, Disalvatore S, Liu D, Duvic M, Schwartz JD, Konopleva M (2015) Lead-in stage results of a pivotal trial of SL-401, an interleukin-3 receptor (IL-3R) targeting biologic, in patients with blastic plasmacytoid dendritic cell neoplasm (BPDCN) or acute myeloid leukemia (AML) [abstract]. Blood 126(23):3795
74.
Zurück zum Zitat Schwartz MA, Lovett DR, Redner A, Finn RD, Graham MC, Divgi CR, Dantis L, Gee TS, Andreeff M, Old LJ et al (1993) Dose-escalation trial of M195 labeled with iodine 131 for cytoreduction and marrow ablation in relapsed or refractory myeloid leukemias. J Clin Oncol 11(2):294–303PubMedCrossRef Schwartz MA, Lovett DR, Redner A, Finn RD, Graham MC, Divgi CR, Dantis L, Gee TS, Andreeff M, Old LJ et al (1993) Dose-escalation trial of M195 labeled with iodine 131 for cytoreduction and marrow ablation in relapsed or refractory myeloid leukemias. J Clin Oncol 11(2):294–303PubMedCrossRef
76.
Zurück zum Zitat Pagel JM, Gooley TA, Rajendran J, Fisher DR, Wilson WA, Sandmaier BM, Matthews DC, Deeg HJ, Gopal AK, Martin PJ, Storb RF, Press OW, Appelbaum FR (2009) Allogeneic hematopoietic cell transplantation after conditioning with 131I-anti-CD45 antibody plus fludarabine and low-dose total body irradiation for elderly patients with advanced acute myeloid leukemia or high-risk myelodysplastic syndrome. Blood 114(27):5444–5453. https://doi.org/10.1182/blood-2009-03-213298 PubMedPubMedCentralCrossRef Pagel JM, Gooley TA, Rajendran J, Fisher DR, Wilson WA, Sandmaier BM, Matthews DC, Deeg HJ, Gopal AK, Martin PJ, Storb RF, Press OW, Appelbaum FR (2009) Allogeneic hematopoietic cell transplantation after conditioning with 131I-anti-CD45 antibody plus fludarabine and low-dose total body irradiation for elderly patients with advanced acute myeloid leukemia or high-risk myelodysplastic syndrome. Blood 114(27):5444–5453. https://​doi.​org/​10.​1182/​blood-2009-03-213298 PubMedPubMedCentralCrossRef
77.
Zurück zum Zitat Pagel JM, Appelbaum FR, Eary JF, Rajendran J, Fisher DR, Gooley T, Ruffner K, Nemecek E, Sickle E, Durack L, Carreras J, Horowitz MM, Press OW, Gopal AK, Martin PJ, Bernstein ID, Matthews DC (2006) 131I-anti-CD45 antibody plus busulfan and cyclophosphamide before allogeneic hematopoietic cell transplantation for treatment of acute myeloid leukemia in first remission. Blood 107(5):2184–2191. https://doi.org/10.1182/blood-2005-06-2317 PubMedPubMedCentralCrossRef Pagel JM, Appelbaum FR, Eary JF, Rajendran J, Fisher DR, Gooley T, Ruffner K, Nemecek E, Sickle E, Durack L, Carreras J, Horowitz MM, Press OW, Gopal AK, Martin PJ, Bernstein ID, Matthews DC (2006) 131I-anti-CD45 antibody plus busulfan and cyclophosphamide before allogeneic hematopoietic cell transplantation for treatment of acute myeloid leukemia in first remission. Blood 107(5):2184–2191. https://​doi.​org/​10.​1182/​blood-2005-06-2317 PubMedPubMedCentralCrossRef
78.
Zurück zum Zitat Burke JM, Caron PC, Papadopoulos EB, Divgi CR, Sgouros G, Panageas KS, Finn RD, Larson SM, O'Reilly RJ, Scheinberg DA, Jurcic JG (2003) Cytoreduction with iodine-131-anti-CD33 antibodies before bone marrow transplantation for advanced myeloid leukemias. Bone Marrow Transplant 32(6):549–556. https://doi.org/10.1038/sj.bmt.1704201 PubMedCrossRef Burke JM, Caron PC, Papadopoulos EB, Divgi CR, Sgouros G, Panageas KS, Finn RD, Larson SM, O'Reilly RJ, Scheinberg DA, Jurcic JG (2003) Cytoreduction with iodine-131-anti-CD33 antibodies before bone marrow transplantation for advanced myeloid leukemias. Bone Marrow Transplant 32(6):549–556. https://​doi.​org/​10.​1038/​sj.​bmt.​1704201 PubMedCrossRef
79.
Zurück zum Zitat Jurcic JG, Larson SM, Sgouros G, McDevitt MR, Finn RD, Divgi CR, Ballangrud AM, Hamacher KA, Ma D, Humm JL, Brechbiel MW, Molinet R, Scheinberg DA (2002) Targeted alpha particle immunotherapy for myeloid leukemia. Blood 100(4):1233–1239PubMed Jurcic JG, Larson SM, Sgouros G, McDevitt MR, Finn RD, Divgi CR, Ballangrud AM, Hamacher KA, Ma D, Humm JL, Brechbiel MW, Molinet R, Scheinberg DA (2002) Targeted alpha particle immunotherapy for myeloid leukemia. Blood 100(4):1233–1239PubMed
80.
Zurück zum Zitat Jurcic JG, Levy MY, Park JH, Ravandi F, Perl AE, Pagel JM, Smith BD, Estey EH, Kantarjian H, Cicic D, Scheinberg DA (2016) Phase I trial of targeted alpha-particle therapy with actinium-225 (225Ac)-lintuzumab and low-dose cytarabine (LDAC) in patients age 60 or older with untreated acute myeloid leukemia (AML) [abstract]. Blood 128(22):4050 Jurcic JG, Levy MY, Park JH, Ravandi F, Perl AE, Pagel JM, Smith BD, Estey EH, Kantarjian H, Cicic D, Scheinberg DA (2016) Phase I trial of targeted alpha-particle therapy with actinium-225 (225Ac)-lintuzumab and low-dose cytarabine (LDAC) in patients age 60 or older with untreated acute myeloid leukemia (AML) [abstract]. Blood 128(22):4050
82.
Zurück zum Zitat Topp MS, Kufer P, Gokbuget N, Goebeler M, Klinger M, Neumann S, Horst HA, Raff T, Viardot A, Schmid M, Stelljes M, Schaich M, Degenhard E, Kohne-Volland R, Bruggemann M, Ottmann O, Pfeifer H, Burmeister T, Nagorsen D, Schmidt M, Lutterbuese R, Reinhardt C, Baeuerle PA, Kneba M, Einsele H, Riethmuller G, Hoelzer D, Zugmaier G, Bargou RC (2011) Targeted therapy with the T-cell-engaging antibody blinatumomab of chemotherapy-refractory minimal residual disease in B-lineage acute lymphoblastic leukemia patients results in high response rate and prolonged leukemia-free survival. J Clin Oncol 29(18):2493–2498. https://doi.org/10.1200/jco.2010.32.7270 PubMedCrossRef Topp MS, Kufer P, Gokbuget N, Goebeler M, Klinger M, Neumann S, Horst HA, Raff T, Viardot A, Schmid M, Stelljes M, Schaich M, Degenhard E, Kohne-Volland R, Bruggemann M, Ottmann O, Pfeifer H, Burmeister T, Nagorsen D, Schmidt M, Lutterbuese R, Reinhardt C, Baeuerle PA, Kneba M, Einsele H, Riethmuller G, Hoelzer D, Zugmaier G, Bargou RC (2011) Targeted therapy with the T-cell-engaging antibody blinatumomab of chemotherapy-refractory minimal residual disease in B-lineage acute lymphoblastic leukemia patients results in high response rate and prolonged leukemia-free survival. J Clin Oncol 29(18):2493–2498. https://​doi.​org/​10.​1200/​jco.​2010.​32.​7270 PubMedCrossRef
83.
Zurück zum Zitat Krupka C, Kufer P, Kischel R, Zugmaier G, Bogeholz J, Kohnke T, Lichtenegger FS, Schneider S, Metzeler KH, Fiegl M, Spiekermann K, Baeuerle PA, Hiddemann W, Riethmuller G, Subklewe M (2014) CD33 target validation and sustained depletion of AML blasts in long-term cultures by the bispecific T-cell-engaging antibody AMG 330. Blood 123(3):356–365. https://doi.org/10.1182/blood-2013-08-523548 PubMedCrossRef Krupka C, Kufer P, Kischel R, Zugmaier G, Bogeholz J, Kohnke T, Lichtenegger FS, Schneider S, Metzeler KH, Fiegl M, Spiekermann K, Baeuerle PA, Hiddemann W, Riethmuller G, Subklewe M (2014) CD33 target validation and sustained depletion of AML blasts in long-term cultures by the bispecific T-cell-engaging antibody AMG 330. Blood 123(3):356–365. https://​doi.​org/​10.​1182/​blood-2013-08-523548 PubMedCrossRef
85.
Zurück zum Zitat Johnson S, Burke S, Huang L, Gorlatov S, Li H, Wang W, Zhang W, Tuaillon N, Rainey J, Barat B, Yang Y, Jin L, Ciccarone V, Moore PA, Koenig S, Bonvini E (2010) Effector cell recruitment with novel Fv-based dual-affinity re-targeting protein leads to potent tumor cytolysis and in vivo B-cell depletion. J Mol Biol 399(3):436–449. https://doi.org/10.1016/j.jmb.2010.04.001 PubMedCrossRef Johnson S, Burke S, Huang L, Gorlatov S, Li H, Wang W, Zhang W, Tuaillon N, Rainey J, Barat B, Yang Y, Jin L, Ciccarone V, Moore PA, Koenig S, Bonvini E (2010) Effector cell recruitment with novel Fv-based dual-affinity re-targeting protein leads to potent tumor cytolysis and in vivo B-cell depletion. J Mol Biol 399(3):436–449. https://​doi.​org/​10.​1016/​j.​jmb.​2010.​04.​001 PubMedCrossRef
87.
Zurück zum Zitat Rosenberg SA, Lotze MT, Yang JC, Topalian SL, Chang AE, Schwartzentruber DJ, Aebersold P, Leitman S, Linehan WM, Seipp CA et al (1993) Prospective randomized trial of high-dose interleukin-2 alone or in conjunction with lymphokine-activated killer cells for the treatment of patients with advanced cancer. J Natl Cancer Inst 85(8):622–632PubMedCrossRef Rosenberg SA, Lotze MT, Yang JC, Topalian SL, Chang AE, Schwartzentruber DJ, Aebersold P, Leitman S, Linehan WM, Seipp CA et al (1993) Prospective randomized trial of high-dose interleukin-2 alone or in conjunction with lymphokine-activated killer cells for the treatment of patients with advanced cancer. J Natl Cancer Inst 85(8):622–632PubMedCrossRef
88.
Zurück zum Zitat Rosenberg SA, Lotze MT, Muul LM, Chang AE, Avis FP, Leitman S, Linehan WM, Robertson CN, Lee RE, Rubin JT et al (1987) A progress report on the treatment of 157 patients with advanced cancer using lymphokine-activated killer cells and interleukin-2 or high-dose interleukin-2 alone. N Engl J Med 316(15):889–897. https://doi.org/10.1056/nejm198704093161501 PubMedCrossRef Rosenberg SA, Lotze MT, Muul LM, Chang AE, Avis FP, Leitman S, Linehan WM, Robertson CN, Lee RE, Rubin JT et al (1987) A progress report on the treatment of 157 patients with advanced cancer using lymphokine-activated killer cells and interleukin-2 or high-dose interleukin-2 alone. N Engl J Med 316(15):889–897. https://​doi.​org/​10.​1056/​nejm198704093161​501 PubMedCrossRef
89.
Zurück zum Zitat Ettinghausen SE, Lipford EH 3rd, Mule JJ, Rosenberg SA (1985) Recombinant interleukin 2 stimulates in vivo proliferation of adoptively transferred lymphokine-activated killer (LAK) cells. J Immunol 135(5):3623–3635PubMed Ettinghausen SE, Lipford EH 3rd, Mule JJ, Rosenberg SA (1985) Recombinant interleukin 2 stimulates in vivo proliferation of adoptively transferred lymphokine-activated killer (LAK) cells. J Immunol 135(5):3623–3635PubMed
90.
Zurück zum Zitat Thatcher N, Dazzi H, Johnson RJ, Russell S, Ghosh AK, Moore M, Chadwick G, Craig RD (1989) Recombinant interleukin-2 (rIL-2) given intrasplenically and intravenously for advanced malignant melanoma. A phase I and II study. Br J Cancer 60(5):770–774PubMedPubMedCentralCrossRef Thatcher N, Dazzi H, Johnson RJ, Russell S, Ghosh AK, Moore M, Chadwick G, Craig RD (1989) Recombinant interleukin-2 (rIL-2) given intrasplenically and intravenously for advanced malignant melanoma. A phase I and II study. Br J Cancer 60(5):770–774PubMedPubMedCentralCrossRef
91.
Zurück zum Zitat Lu PH, Negrin RS (1994) A novel population of expanded human CD3+CD56+ cells derived from T cells with potent in vivo antitumor activity in mice with severe combined immunodeficiency. J Immunol 153(4):1687–1696PubMed Lu PH, Negrin RS (1994) A novel population of expanded human CD3+CD56+ cells derived from T cells with potent in vivo antitumor activity in mice with severe combined immunodeficiency. J Immunol 153(4):1687–1696PubMed
93.
Zurück zum Zitat Noonan KA, Huff CA, Davis J, Lemas MV, Fiorino S, Bitzan J, Ferguson A, Emerling A, Luznik L, Matsui W, Powell J, Fuchs E, Rosner GL, Epstein C, Rudraraju L, Ambinder RF, Jones RJ, Pardoll D, Borrello I (2015) Adoptive transfer of activated marrow-infiltrating lymphocytes induces measurable antitumor immunity in the bone marrow in multiple myeloma. Sci Transl Med 7(288):288ra278. https://doi.org/10.1126/scitranslmed.aaa7014 CrossRef Noonan KA, Huff CA, Davis J, Lemas MV, Fiorino S, Bitzan J, Ferguson A, Emerling A, Luznik L, Matsui W, Powell J, Fuchs E, Rosner GL, Epstein C, Rudraraju L, Ambinder RF, Jones RJ, Pardoll D, Borrello I (2015) Adoptive transfer of activated marrow-infiltrating lymphocytes induces measurable antitumor immunity in the bone marrow in multiple myeloma. Sci Transl Med 7(288):288ra278. https://​doi.​org/​10.​1126/​scitranslmed.​aaa7014 CrossRef
95.
Zurück zum Zitat Amir AL, van der Steen DM, van Loenen MM, Hagedoorn RS, de Boer R, Kester MD, de Ru AH, Lugthart GJ, van Kooten C, Hiemstra PS, Jedema I, Griffioen M, van Veelen PA, Falkenburg JH, Heemskerk MH (2011) PRAME-specific Allo-HLA-restricted T cells with potent antitumor reactivity useful for therapeutic T-cell receptor gene transfer. Clin Cancer Res 17(17):5615–5625. https://doi.org/10.1158/1078-0432.ccr-11-1066 PubMedCrossRef Amir AL, van der Steen DM, van Loenen MM, Hagedoorn RS, de Boer R, Kester MD, de Ru AH, Lugthart GJ, van Kooten C, Hiemstra PS, Jedema I, Griffioen M, van Veelen PA, Falkenburg JH, Heemskerk MH (2011) PRAME-specific Allo-HLA-restricted T cells with potent antitumor reactivity useful for therapeutic T-cell receptor gene transfer. Clin Cancer Res 17(17):5615–5625. https://​doi.​org/​10.​1158/​1078-0432.​ccr-11-1066 PubMedCrossRef
98.
Zurück zum Zitat Ruggeri L, Capanni M, Urbani E, Perruccio K, Shlomchik WD, Tosti A, Posati S, Rogaia D, Frassoni F, Aversa F, Martelli MF, Velardi A (2002) Effectiveness of donor natural killer cell alloreactivity in mismatched hematopoietic transplants. Science (New York, NY) 295(5562):2097–2100. https://doi.org/10.1126/science.1068440 CrossRef Ruggeri L, Capanni M, Urbani E, Perruccio K, Shlomchik WD, Tosti A, Posati S, Rogaia D, Frassoni F, Aversa F, Martelli MF, Velardi A (2002) Effectiveness of donor natural killer cell alloreactivity in mismatched hematopoietic transplants. Science (New York, NY) 295(5562):2097–2100. https://​doi.​org/​10.​1126/​science.​1068440 CrossRef
99.
Zurück zum Zitat Choi I, Yoon SR, Park SY, Kim H, Jung SJ, Jang YJ, Kang M, Yeom YI, Lee JL, Kim DY, Lee YS, Kang YA, Jeon M, Seol M, Lee JH, Lee JH, Kim HJ, Yun SC, Lee KH (2014) Donor-derived natural killer cells infused after human leukocyte antigen-haploidentical hematopoietic cell transplantation: a dose-escalation study. Biol Blood Marrow Transplant 20(5):696–704. https://doi.org/10.1016/j.bbmt.2014.01.031 PubMedCrossRef Choi I, Yoon SR, Park SY, Kim H, Jung SJ, Jang YJ, Kang M, Yeom YI, Lee JL, Kim DY, Lee YS, Kang YA, Jeon M, Seol M, Lee JH, Lee JH, Kim HJ, Yun SC, Lee KH (2014) Donor-derived natural killer cells infused after human leukocyte antigen-haploidentical hematopoietic cell transplantation: a dose-escalation study. Biol Blood Marrow Transplant 20(5):696–704. https://​doi.​org/​10.​1016/​j.​bbmt.​2014.​01.​031 PubMedCrossRef
101.
Zurück zum Zitat Sandoval-Borrego D, Moreno-Lafont MC, Vazquez-Sanchez EA, Gutierrez-Hoya A, Lopez-Santiago R, Montiel-Cervantes LA, Ramirez-Saldana M, Vela-Ojeda J (2016) Overexpression of CD158 and NKG2A inhibitory receptors and underexpression of NKG2D and NKp46 activating receptors on NK cells in acute myeloid leukemia. Arch Med Res 47(1):55–64. https://doi.org/10.1016/j.arcmed.2016.02.001 PubMedCrossRef Sandoval-Borrego D, Moreno-Lafont MC, Vazquez-Sanchez EA, Gutierrez-Hoya A, Lopez-Santiago R, Montiel-Cervantes LA, Ramirez-Saldana M, Vela-Ojeda J (2016) Overexpression of CD158 and NKG2A inhibitory receptors and underexpression of NKG2D and NKp46 activating receptors on NK cells in acute myeloid leukemia. Arch Med Res 47(1):55–64. https://​doi.​org/​10.​1016/​j.​arcmed.​2016.​02.​001 PubMedCrossRef
103.
Zurück zum Zitat Stern M, Passweg JR, Meyer-Monard S, Esser R, Tonn T, Soerensen J, Paulussen M, Gratwohl A, Klingebiel T, Bader P, Tichelli A, Schwabe D, Koehl U (2013) Pre-emptive immunotherapy with purified natural killer cells after haploidentical SCT: a prospective phase II study in two centers. Bone Marrow Transplant 48(3):433–438. https://doi.org/10.1038/bmt.2012.162 PubMedCrossRef Stern M, Passweg JR, Meyer-Monard S, Esser R, Tonn T, Soerensen J, Paulussen M, Gratwohl A, Klingebiel T, Bader P, Tichelli A, Schwabe D, Koehl U (2013) Pre-emptive immunotherapy with purified natural killer cells after haploidentical SCT: a prospective phase II study in two centers. Bone Marrow Transplant 48(3):433–438. https://​doi.​org/​10.​1038/​bmt.​2012.​162 PubMedCrossRef
111.
Zurück zum Zitat Linn YC, Niam M, Chu S, Choong A, Yong HX, Heng KK, Hwang W, Loh Y, Goh YT, Suck G, Chan M, Koh M (2012) The anti-tumour activity of allogeneic cytokine-induced killer cells in patients who relapse after allogeneic transplant for haematological malignancies. Bone Marrow Transplant 47(7):957–966. https://doi.org/10.1038/bmt.2011.202 PubMedCrossRef Linn YC, Niam M, Chu S, Choong A, Yong HX, Heng KK, Hwang W, Loh Y, Goh YT, Suck G, Chan M, Koh M (2012) The anti-tumour activity of allogeneic cytokine-induced killer cells in patients who relapse after allogeneic transplant for haematological malignancies. Bone Marrow Transplant 47(7):957–966. https://​doi.​org/​10.​1038/​bmt.​2011.​202 PubMedCrossRef
112.
Zurück zum Zitat Zhong ZD, Luo Y, Zou P, Zheng JE, Yao JX, Huang SA, Zhou DF, You Y (2012) Infusions of recipient-derived cytokine-induced killer cells of donor origin eradicated residual disease in a relapsed leukemia patient after allo-hematopoietic stem cell transplantation. Chin Med J 125(9):1669–1671PubMed Zhong ZD, Luo Y, Zou P, Zheng JE, Yao JX, Huang SA, Zhou DF, You Y (2012) Infusions of recipient-derived cytokine-induced killer cells of donor origin eradicated residual disease in a relapsed leukemia patient after allo-hematopoietic stem cell transplantation. Chin Med J 125(9):1669–1671PubMed
113.
Zurück zum Zitat Marten A, Renoth S, von Lilienfeld-Toal M, Buttgereit P, Schakowski F, Glasmacher A, Sauerbruch T, Schmidt-Wolf IG (2001) Enhanced lytic activity of cytokine-induced killer cells against multiple myeloma cells after co-culture with idiotype-pulsed dendritic cells. Haematologica 86(10):1029–1037PubMed Marten A, Renoth S, von Lilienfeld-Toal M, Buttgereit P, Schakowski F, Glasmacher A, Sauerbruch T, Schmidt-Wolf IG (2001) Enhanced lytic activity of cytokine-induced killer cells against multiple myeloma cells after co-culture with idiotype-pulsed dendritic cells. Haematologica 86(10):1029–1037PubMed
115.
Zurück zum Zitat Chan JK, Hamilton CA, Cheung MK, Karimi M, Baker J, Gall JM, Schulz S, Thorne SH, Teng NN, Contag CH, Lum LG, Negrin RS (2006) Enhanced killing of primary ovarian cancer by retargeting autologous cytokine-induced killer cells with bispecific antibodies: a preclinical study. Clin Cancer Res 12(6):1859–1867. https://doi.org/10.1158/1078-0432.ccr-05-2019 PubMedCrossRef Chan JK, Hamilton CA, Cheung MK, Karimi M, Baker J, Gall JM, Schulz S, Thorne SH, Teng NN, Contag CH, Lum LG, Negrin RS (2006) Enhanced killing of primary ovarian cancer by retargeting autologous cytokine-induced killer cells with bispecific antibodies: a preclinical study. Clin Cancer Res 12(6):1859–1867. https://​doi.​org/​10.​1158/​1078-0432.​ccr-05-2019 PubMedCrossRef
121.
Zurück zum Zitat Geiger TL, Rubnitz JE (2015) New approaches for the immunotherapy of acute myeloid leukemia. Discov Med 19(105):275–284PubMedPubMedCentral Geiger TL, Rubnitz JE (2015) New approaches for the immunotherapy of acute myeloid leukemia. Discov Med 19(105):275–284PubMedPubMedCentral
122.
123.
Zurück zum Zitat Davila ML, Riviere I, Wang X, Bartido S, Park J, Curran K, Chung SS, Stefanski J, Borquez-Ojeda O, Olszewska M, Qu J, Wasielewska T, He Q, Fink M, Shinglot H, Youssif M, Satter M, Wang Y, Hosey J, Quintanilla H, Halton E, Bernal Y, Bouhassira DC, Arcila ME, Gonen M, Roboz GJ, Maslak P, Douer D, Frattini MG, Giralt S, Sadelain M, Brentjens R (2014) Efficacy and toxicity management of 19-28z CAR T cell therapy in B cell acute lymphoblastic leukemia. Sci Transl Med 6(224):224ra225. https://doi.org/10.1126/scitranslmed.3008226 CrossRef Davila ML, Riviere I, Wang X, Bartido S, Park J, Curran K, Chung SS, Stefanski J, Borquez-Ojeda O, Olszewska M, Qu J, Wasielewska T, He Q, Fink M, Shinglot H, Youssif M, Satter M, Wang Y, Hosey J, Quintanilla H, Halton E, Bernal Y, Bouhassira DC, Arcila ME, Gonen M, Roboz GJ, Maslak P, Douer D, Frattini MG, Giralt S, Sadelain M, Brentjens R (2014) Efficacy and toxicity management of 19-28z CAR T cell therapy in B cell acute lymphoblastic leukemia. Sci Transl Med 6(224):224ra225. https://​doi.​org/​10.​1126/​scitranslmed.​3008226 CrossRef
126.
Zurück zum Zitat Hoang T, Foster A, Crisostomo J, Lu A, Moseley A, Heemskerk MHM, Slawin KM, Spencer DM (2015) Inducible MyD88/CD40 enhances proliferation and survival of PRAME-specific TCR-engineered T cells and increases anti-tumor effects in myeloma [abstract]. Blood 126(23):1886 Hoang T, Foster A, Crisostomo J, Lu A, Moseley A, Heemskerk MHM, Slawin KM, Spencer DM (2015) Inducible MyD88/CD40 enhances proliferation and survival of PRAME-specific TCR-engineered T cells and increases anti-tumor effects in myeloma [abstract]. Blood 126(23):1886
127.
128.
Zurück zum Zitat Tawara I, Masuya M, Kageyama S, Nishida T, Terakura S, Murata M, Fujiwara H, Akatsuka Y, Ikeda H, Miyahara Y, Tomura D, Nukaya I, Takesako K, Emi N, Yasukawa M, Katayama N, Shiku H (2015) Adoptive transfer of WT1-specific TCR gene-transduced lymphocytes in patients with myelodysplastic syndrome and acute myeloid leukemia [abstract]. Blood 126(23):97 Tawara I, Masuya M, Kageyama S, Nishida T, Terakura S, Murata M, Fujiwara H, Akatsuka Y, Ikeda H, Miyahara Y, Tomura D, Nukaya I, Takesako K, Emi N, Yasukawa M, Katayama N, Shiku H (2015) Adoptive transfer of WT1-specific TCR gene-transduced lymphocytes in patients with myelodysplastic syndrome and acute myeloid leukemia [abstract]. Blood 126(23):97
129.
Zurück zum Zitat Tanimoto K, Fujiwara H, Tawara I, Masuya M, Kageyama S, Nishida T, Murata M, Terakura S, Akatsuka Y, Ikeda H, Miyahara Y, Nukaya I, Takesako K, Emi N, Katayama N, Shiku H, Yasukawa M (2016) Phase 1 clinical trial of adoptive immunotherapy for acute myelogenous leukemia and myelodysplastic syndrome, using gene-modified autologous lymphocytes expressing WT1-specific T-cell receptor [abstract]. Blood 128(22):1653 Tanimoto K, Fujiwara H, Tawara I, Masuya M, Kageyama S, Nishida T, Murata M, Terakura S, Akatsuka Y, Ikeda H, Miyahara Y, Nukaya I, Takesako K, Emi N, Katayama N, Shiku H, Yasukawa M (2016) Phase 1 clinical trial of adoptive immunotherapy for acute myelogenous leukemia and myelodysplastic syndrome, using gene-modified autologous lymphocytes expressing WT1-specific T-cell receptor [abstract]. Blood 128(22):1653
130.
Zurück zum Zitat Ikeda H, Akahori Y, Yoneyama M, Orito Y, Miyahara Y, Amaishi Y, Okamoto S, Mineno J, Takesako K, Fujiwara H, Yasukawa M, Shiku H (2015) Immunotherapy with chimeric antigen receptor targeting intracellular WT1 gene product complexed with HLA-a*24:02 molecule [abstract]. Blood 126(23):4292 Ikeda H, Akahori Y, Yoneyama M, Orito Y, Miyahara Y, Amaishi Y, Okamoto S, Mineno J, Takesako K, Fujiwara H, Yasukawa M, Shiku H (2015) Immunotherapy with chimeric antigen receptor targeting intracellular WT1 gene product complexed with HLA-a*24:02 molecule [abstract]. Blood 126(23):4292
131.
Zurück zum Zitat Campillo-Davo D, Fujiki F, Bergh JMJVd, Smits EL, Sugiyama H, Tendeloo VFIV, Berneman ZN (2016) Electroporation of Dicer-substrate siRNA duplexes targeting endogenous TCR enhance tumor killing activity of Wilms’ tumor 1 (WT1)-specific TCR-redirected cytotoxic T cells [abstract]. Blood 128(22):813 Campillo-Davo D, Fujiki F, Bergh JMJVd, Smits EL, Sugiyama H, Tendeloo VFIV, Berneman ZN (2016) Electroporation of Dicer-substrate siRNA duplexes targeting endogenous TCR enhance tumor killing activity of Wilms’ tumor 1 (WT1)-specific TCR-redirected cytotoxic T cells [abstract]. Blood 128(22):813
132.
Zurück zum Zitat Ritchie DS, Neeson PJ, Khot A, Peinert S, Tai T, Tainton K, Chen K, Shin M, Wall DM, Honemann D, Gambell P, Westerman DA, Haurat J, Westwood JA, Scott AM, Kravets L, Dickinson M, Trapani JA, Smyth MJ, Darcy PK, Kershaw MH, Prince HM (2013) Persistence and efficacy of second generation CAR T cell against the LeY antigen in acute myeloid leukemia. Mol Ther 21(11):2122–2129. https://doi.org/10.1038/mt.2013.154 PubMedPubMedCentralCrossRef Ritchie DS, Neeson PJ, Khot A, Peinert S, Tai T, Tainton K, Chen K, Shin M, Wall DM, Honemann D, Gambell P, Westerman DA, Haurat J, Westwood JA, Scott AM, Kravets L, Dickinson M, Trapani JA, Smyth MJ, Darcy PK, Kershaw MH, Prince HM (2013) Persistence and efficacy of second generation CAR T cell against the LeY antigen in acute myeloid leukemia. Mol Ther 21(11):2122–2129. https://​doi.​org/​10.​1038/​mt.​2013.​154 PubMedPubMedCentralCrossRef
133.
Zurück zum Zitat Mardiros A, Dos Santos C, McDonald T, Brown CE, Wang X, Budde LE, Hoffman L, Aguilar B, Chang WC, Bretzlaff W, Chang B, Jonnalagadda M, Starr R, Ostberg JR, Jensen MC, Bhatia R, Forman SJ (2013) T cells expressing CD123-specific chimeric antigen receptors exhibit specific cytolytic effector functions and antitumor effects against human acute myeloid leukemia. Blood 122(18):3138–3148. https://doi.org/10.1182/blood-2012-12-474056 PubMedPubMedCentralCrossRef Mardiros A, Dos Santos C, McDonald T, Brown CE, Wang X, Budde LE, Hoffman L, Aguilar B, Chang WC, Bretzlaff W, Chang B, Jonnalagadda M, Starr R, Ostberg JR, Jensen MC, Bhatia R, Forman SJ (2013) T cells expressing CD123-specific chimeric antigen receptors exhibit specific cytolytic effector functions and antitumor effects against human acute myeloid leukemia. Blood 122(18):3138–3148. https://​doi.​org/​10.​1182/​blood-2012-12-474056 PubMedPubMedCentralCrossRef
134.
Zurück zum Zitat Casucci M, Nicolis di Robilant B, Falcone L, Camisa B, Norelli M, Genovese P, Gentner B, Gullotta F, Ponzoni M, Bernardi M, Marcatti M, Saudemont A, Bordignon C, Savoldo B, Ciceri F, Naldini L, Dotti G, Bonini C, Bondanza A (2013) CD44v6-targeted T cells mediate potent antitumor effects against acute myeloid leukemia and multiple myeloma. Blood 122(20):3461–3472. https://doi.org/10.1182/blood-2013-04-493361 PubMedCrossRef Casucci M, Nicolis di Robilant B, Falcone L, Camisa B, Norelli M, Genovese P, Gentner B, Gullotta F, Ponzoni M, Bernardi M, Marcatti M, Saudemont A, Bordignon C, Savoldo B, Ciceri F, Naldini L, Dotti G, Bonini C, Bondanza A (2013) CD44v6-targeted T cells mediate potent antitumor effects against acute myeloid leukemia and multiple myeloma. Blood 122(20):3461–3472. https://​doi.​org/​10.​1182/​blood-2013-04-493361 PubMedCrossRef
135.
Zurück zum Zitat Miyazaki Y, Fujiwara H, Asai H, Ochi F, Ochi T, Azuma T, Ishida T, Okamoto S, Mineno J, Kuzushima K, Shiku H, Yasukawa M (2013) Development of a novel redirected T-cell-based adoptive immunotherapy targeting human telomerase reverse transcriptase for adult T-cell leukemia. Blood 121(24):4894–4901. https://doi.org/10.1182/blood-2012-11-465971 PubMedCrossRef Miyazaki Y, Fujiwara H, Asai H, Ochi F, Ochi T, Azuma T, Ishida T, Okamoto S, Mineno J, Kuzushima K, Shiku H, Yasukawa M (2013) Development of a novel redirected T-cell-based adoptive immunotherapy targeting human telomerase reverse transcriptase for adult T-cell leukemia. Blood 121(24):4894–4901. https://​doi.​org/​10.​1182/​blood-2012-11-465971 PubMedCrossRef
136.
Zurück zum Zitat Bigalke I, Honnashagen K, Lundby M, Kasten J, Inderberg EMS, Skoge L, Saboe-Larssen S, Schendel DJ, Kvalheim G (2014) Vaccination with a new generation of fast dendritic cells transfected with mRNA from hTERT, survivin and autologous tumor mount strong immune responses and prolong survival [abstract]. Blood 124(21):2440 Bigalke I, Honnashagen K, Lundby M, Kasten J, Inderberg EMS, Skoge L, Saboe-Larssen S, Schendel DJ, Kvalheim G (2014) Vaccination with a new generation of fast dendritic cells transfected with mRNA from hTERT, survivin and autologous tumor mount strong immune responses and prolong survival [abstract]. Blood 124(21):2440
139.
Zurück zum Zitat Hodi FS, O'Day SJ, McDermott DF, Weber RW, Sosman JA, Haanen JB, Gonzalez R, Robert C, Schadendorf D, Hassel JC, Akerley W, van den Eertwegh AJ, Lutzky J, Lorigan P, Vaubel JM, Linette GP, Hogg D, Ottensmeier CH, Lebbe C, Peschel C, Quirt I, Clark JI, Wolchok JD, Weber JS, Tian J, Yellin MJ, Nichol GM, Hoos A, Urba WJ (2010) Improved survival with ipilimumab in patients with metastatic melanoma. N Engl J Med 363(8):711–723. https://doi.org/10.1056/NEJMoa1003466 PubMedPubMedCentralCrossRef Hodi FS, O'Day SJ, McDermott DF, Weber RW, Sosman JA, Haanen JB, Gonzalez R, Robert C, Schadendorf D, Hassel JC, Akerley W, van den Eertwegh AJ, Lutzky J, Lorigan P, Vaubel JM, Linette GP, Hogg D, Ottensmeier CH, Lebbe C, Peschel C, Quirt I, Clark JI, Wolchok JD, Weber JS, Tian J, Yellin MJ, Nichol GM, Hoos A, Urba WJ (2010) Improved survival with ipilimumab in patients with metastatic melanoma. N Engl J Med 363(8):711–723. https://​doi.​org/​10.​1056/​NEJMoa1003466 PubMedPubMedCentralCrossRef
140.
Zurück zum Zitat LaBelle JL, Hanke CA, Blazar BR, Truitt RL (2002) Negative effect of CTLA-4 on induction of T-cell immunity in vivo to B7-1+, but not B7-2+, murine myelogenous leukemia. Blood 99(6):2146–2153PubMedCrossRef LaBelle JL, Hanke CA, Blazar BR, Truitt RL (2002) Negative effect of CTLA-4 on induction of T-cell immunity in vivo to B7-1+, but not B7-2+, murine myelogenous leukemia. Blood 99(6):2146–2153PubMedCrossRef
141.
Zurück zum Zitat Fevery S, Billiau AD, Sprangers B, Rutgeerts O, Lenaerts C, Goebels J, Landuyt W, Kasran A, Boon L, Sagaert X, De Wolf-Peeters C, Waer M, Vandenberghe P (2007) CTLA-4 blockade in murine bone marrow chimeras induces a host-derived antileukemic effect without graft-versus-host disease. Leukemia 21(7):1451–1459. https://doi.org/10.1038/sj.leu.2404720 PubMedCrossRef Fevery S, Billiau AD, Sprangers B, Rutgeerts O, Lenaerts C, Goebels J, Landuyt W, Kasran A, Boon L, Sagaert X, De Wolf-Peeters C, Waer M, Vandenberghe P (2007) CTLA-4 blockade in murine bone marrow chimeras induces a host-derived antileukemic effect without graft-versus-host disease. Leukemia 21(7):1451–1459. https://​doi.​org/​10.​1038/​sj.​leu.​2404720 PubMedCrossRef
142.
Zurück zum Zitat Davids MS, Kim HT, Bachireddy P, Costello C, Liguori R, Savell A, Lukez AP, Avigan D, Chen YB, McSweeney P, LeBoeuf NR, Rooney MS, Bowden M, Zhou CW, Granter SR, Hornick JL, Rodig SJ, Hirakawa M, Severgnini M, Hodi FS, CJ W, Ho VT, Cutler C, Koreth J, Alyea EP, Antin JH, Armand P, Streicher H, Ball ED, Ritz J, Bashey A, Soiffer RJ (2016) Ipilimumab for patients with relapse after allogeneic transplantation. N Engl J Med 375(2):143–153. https://doi.org/10.1056/NEJMoa1601202 PubMedPubMedCentralCrossRef Davids MS, Kim HT, Bachireddy P, Costello C, Liguori R, Savell A, Lukez AP, Avigan D, Chen YB, McSweeney P, LeBoeuf NR, Rooney MS, Bowden M, Zhou CW, Granter SR, Hornick JL, Rodig SJ, Hirakawa M, Severgnini M, Hodi FS, CJ W, Ho VT, Cutler C, Koreth J, Alyea EP, Antin JH, Armand P, Streicher H, Ball ED, Ritz J, Bashey A, Soiffer RJ (2016) Ipilimumab for patients with relapse after allogeneic transplantation. N Engl J Med 375(2):143–153. https://​doi.​org/​10.​1056/​NEJMoa1601202 PubMedPubMedCentralCrossRef
145.
147.
150.
Zurück zum Zitat Ley TJ, Miller C, Ding L, Raphael BJ, Mungall AJ, Robertson A, Hoadley K, Triche TJ Jr, Laird PW, Baty JD, Fulton LL, Fulton R, Heath SE, Kalicki-Veizer J, Kandoth C, Klco JM, Koboldt DC, Kanchi KL, Kulkarni S, Lamprecht TL, Larson DE, Lin L, Lu C, McLellan MD, McMichael JF, Payton J, Schmidt H, Spencer DH, Tomasson MH, Wallis JW, Wartman LD, Watson MA, Welch J, Wendl MC, Ally A, Balasundaram M, Birol I, Butterfield Y, Chiu R, Chu A, Chuah E, Chun HJ, Corbett R, Dhalla N, Guin R, He A, Hirst C, Hirst M, Holt RA, Jones S, Karsan A, Lee D, Li HI, Marra MA, Mayo M, Moore RA, Mungall K, Parker J, Pleasance E, Plettner P, Schein J, Stoll D, Swanson L, Tam A, Thiessen N, Varhol R, Wye N, Zhao Y, Gabriel S, Getz G, Sougnez C, Zou L, Leiserson MD, Vandin F, HT W, Applebaum F, Baylin SB, Akbani R, Broom BM, Chen K, Motter TC, Nguyen K, Weinstein JN, Zhang N, Ferguson ML, Adams C, Black A, Bowen J, Gastier-Foster J, Grossman T, Lichtenberg T, Wise L, Davidsen T, Demchok JA, Shaw KR, Sheth M, Sofia HJ, Yang L, Downing JR, Eley G (2013) Genomic and epigenomic landscapes of adult de novo acute myeloid leukemia. N Engl J Med 368(22):2059–2074. https://doi.org/10.1056/NEJMoa1301689 PubMedCrossRef Ley TJ, Miller C, Ding L, Raphael BJ, Mungall AJ, Robertson A, Hoadley K, Triche TJ Jr, Laird PW, Baty JD, Fulton LL, Fulton R, Heath SE, Kalicki-Veizer J, Kandoth C, Klco JM, Koboldt DC, Kanchi KL, Kulkarni S, Lamprecht TL, Larson DE, Lin L, Lu C, McLellan MD, McMichael JF, Payton J, Schmidt H, Spencer DH, Tomasson MH, Wallis JW, Wartman LD, Watson MA, Welch J, Wendl MC, Ally A, Balasundaram M, Birol I, Butterfield Y, Chiu R, Chu A, Chuah E, Chun HJ, Corbett R, Dhalla N, Guin R, He A, Hirst C, Hirst M, Holt RA, Jones S, Karsan A, Lee D, Li HI, Marra MA, Mayo M, Moore RA, Mungall K, Parker J, Pleasance E, Plettner P, Schein J, Stoll D, Swanson L, Tam A, Thiessen N, Varhol R, Wye N, Zhao Y, Gabriel S, Getz G, Sougnez C, Zou L, Leiserson MD, Vandin F, HT W, Applebaum F, Baylin SB, Akbani R, Broom BM, Chen K, Motter TC, Nguyen K, Weinstein JN, Zhang N, Ferguson ML, Adams C, Black A, Bowen J, Gastier-Foster J, Grossman T, Lichtenberg T, Wise L, Davidsen T, Demchok JA, Shaw KR, Sheth M, Sofia HJ, Yang L, Downing JR, Eley G (2013) Genomic and epigenomic landscapes of adult de novo acute myeloid leukemia. N Engl J Med 368(22):2059–2074. https://​doi.​org/​10.​1056/​NEJMoa1301689 PubMedCrossRef
151.
Zurück zum Zitat Dohner H, Estey E, Grimwade D, Amadori S, Appelbaum FR, Buchner T, Dombret H, Ebert BL, Fenaux P, Larson RA, Levine RL, Lo-Coco F, Naoe T, Niederwieser D, Ossenkoppele GJ, Sanz M, Sierra J, Tallman MS, Tien HF, Wei AH, Lowenberg B, Bloomfield CD (2017) Diagnosis and management of AML in adults: 2017 ELN recommendations from an international expert panel. Blood 129(4):424–447. https://doi.org/10.1182/blood-2016-08-733196 PubMedPubMedCentralCrossRef Dohner H, Estey E, Grimwade D, Amadori S, Appelbaum FR, Buchner T, Dombret H, Ebert BL, Fenaux P, Larson RA, Levine RL, Lo-Coco F, Naoe T, Niederwieser D, Ossenkoppele GJ, Sanz M, Sierra J, Tallman MS, Tien HF, Wei AH, Lowenberg B, Bloomfield CD (2017) Diagnosis and management of AML in adults: 2017 ELN recommendations from an international expert panel. Blood 129(4):424–447. https://​doi.​org/​10.​1182/​blood-2016-08-733196 PubMedPubMedCentralCrossRef
152.
Zurück zum Zitat Rotiroti MC, Arcangeli S, Casucci M, Perriello V, Bondanza A, Biondi A, Tettamanti S, Biagi E (2016) Acute myeloid leukemia (AML) targeting by CAR T cells: bridging the gap from preclinical modeling to human studies. Hum Gene Ther. https://doi.org/10.1089/hum.2016.092 Rotiroti MC, Arcangeli S, Casucci M, Perriello V, Bondanza A, Biondi A, Tettamanti S, Biagi E (2016) Acute myeloid leukemia (AML) targeting by CAR T cells: bridging the gap from preclinical modeling to human studies. Hum Gene Ther. https://​doi.​org/​10.​1089/​hum.​2016.​092
154.
Zurück zum Zitat Arndt C, Feldmann A, Koristka S, Cartellieri M, Bonin Mv, Ehninger A, Bornhäuser M, Ehninger G, Bachmann MP (2015) Improved killing of AML blasts by dual-targeting of CD123 and CD33 via Unitarg a novel antibody-based modular T cell retargeting system [abstract]. Blood 126(23):2565 Arndt C, Feldmann A, Koristka S, Cartellieri M, Bonin Mv, Ehninger A, Bornhäuser M, Ehninger G, Bachmann MP (2015) Improved killing of AML blasts by dual-targeting of CD123 and CD33 via Unitarg a novel antibody-based modular T cell retargeting system [abstract]. Blood 126(23):2565
Metadaten
Titel
The progress and current status of immunotherapy in acute myeloid leukemia
verfasst von
Dan Yang
Xiuqun Zhang
Xuezhong Zhang
Yanli Xu
Publikationsdatum
28.10.2017
Verlag
Springer Berlin Heidelberg
Erschienen in
Annals of Hematology / Ausgabe 12/2017
Print ISSN: 0939-5555
Elektronische ISSN: 1432-0584
DOI
https://doi.org/10.1007/s00277-017-3148-x

Weitere Artikel der Ausgabe 12/2017

Annals of Hematology 12/2017 Zur Ausgabe

Leitlinien kompakt für die Innere Medizin

Mit medbee Pocketcards sicher entscheiden.

Seit 2022 gehört die medbee GmbH zum Springer Medizin Verlag

Update Innere Medizin

Bestellen Sie unseren Fach-Newsletter und bleiben Sie gut informiert.