Increasing Role of Targeted Immunotherapies in the Treatment of AML
Abstract
:1. Introduction
2. Immunotherapies Targeting Immunogenic Leukemia-Associated Antigens
2.1. Description of Leukemia-Associated Antigens (LAAs)
2.2. Immunotherapies Targeting LAAs
2.3. Mutation Specific LAAs and Their Therapeutic Potential
3. Immunotherapeutic Strategies Targeting Cell Surface Structures
Antibody-Directed Immunotherapies
4. Immunotherapies with Multiple and Unknown Antigen Structures
5. Immunomodulation in AML
6. Non-Immunogenic Targeted Therapies in AML
7. Conclusions
Supplementary Materials
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Conflicts of Interest
References
- Döhner, H.; Weisdorf, D.J.; Bloomfield, C.D. Acute Myeloid Leukemia. N. Engl. J. Med. 2015, 373, 1136–1152. [Google Scholar] [CrossRef] [Green Version]
- Döhner, H.; Estey, E.; Grimwade, D.; Amadori, S.; Appelbaum, F.R.; Buchner, T.; Dombret, H.; Ebert, B.L.; Fenaux, P.; Larson, R.A.; et al. Diagnosis and management of AML in adults: 2017 ELN recommendations from an international expert panel. Blood 2017, 129, 424–447. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Lee, C.J.; Savani, B.N.; Mohty, M.; Gorin, N.C.; Labopin, M.; Ruggeri, A.; Schmid, C.; Baron, F.; Esteve, J.; Giebel, S.; et al. Post-remission strategies for the prevention of relapse following allogeneic hematopoietic cell transplantation for high-risk acute myeloid leukemia: Expert review from the Acute Leukemia Working Party of the European Society for Blood and Marrow Transplantation. Bone Marrow Transplant. 2019, 54, 519–530. [Google Scholar] [CrossRef]
- Topalian, S.L.; Drake, C.G.; Pardoll, D.M. Immune checkpoint blockade: A common denominator approach to cancer therapy. Cancer Cell 2015, 27, 450–461. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Hude, I.; Sasse, S.; Engert, A.; Brockelmann, P.J. The emerging role of immune checkpoint inhibition in malignant lymphoma. Haematologica 2017, 102, 30–42. [Google Scholar] [CrossRef] [Green Version]
- Gandhi, L.; Rodriguez-Abreu, D.; Gadgeel, S.; Esteban, E.; Felip, E.; De Angelis, F.; Domine, M.; Clingan, P.; Hochmair, M.J.; Powell, S.F.; et al. Pembrolizumab plus Chemotherapy in Metastatic Non-Small-Cell Lung Cancer. N. Engl. J. Med. 2018, 378, 2078–2092. [Google Scholar] [CrossRef] [PubMed]
- Hellmann, M.D.; Ciuleanu, T.E.; Pluzanski, A.; Lee, J.S.; Otterson, G.A.; Audigier-Valette, C.; Minenza, E.; Linardou, H.; Burgers, S.; Salman, P.; et al. Nivolumab plus Ipilimumab in Lung Cancer with a High Tumor Mutational Burden. N. Engl. J. Med. 2018, 378, 2093–2104. [Google Scholar] [CrossRef] [PubMed]
- Kolb, H.J. Hematopoietic stem cell transplantation and cellular therapy. HLA 2017, 89, 267–277. [Google Scholar] [CrossRef]
- Falkenburg, J.H.F.; Jedema, I. Graft versus tumor effects and why people relapse. Educ. Program Am. Soc. Hematol. Am. Soc. Hematol. Educ. Program 2017, 2017, 693–698. [Google Scholar] [CrossRef] [Green Version]
- Vago, L.; Gojo, I. Immune escape and immunotherapy of acute myeloid leukemia. J. Clin. Investig. 2020, 130, 1552–1564. [Google Scholar] [CrossRef]
- Greiner, J. The Important Role of Immunotherapies in Acute Myeloid Leukemia. J. Clin. Med. 2019, 8, 2054. [Google Scholar] [CrossRef] [Green Version]
- Bullinger, L.; Schlenk, R.F.; Gotz, M.; Botzenhardt, U.; Hofmann, S.; Russ, A.C.; Babiak, A.; Zhang, L.; Schneider, V.; Döhner, K.; et al. PRAME-induced inhibition of retinoic acid receptor signaling-mediated differentiation—A possible target for ATRA response in AML without t(15;17). Clin. Cancer Res. 2013, 19, 2562–2571. [Google Scholar] [CrossRef] [Green Version]
- Anguille, S.; Van Tendeloo, V.F.; Berneman, Z.N. Leukemia-associated antigens and their relevance to the immunotherapy of acute myeloid leukemia. Leukemia 2012, 26, 2186–2196. [Google Scholar] [CrossRef] [Green Version]
- Schneider, V.; Zhang, L.; Rojewski, M.; Fekete, N.; Schrezenmeier, H.; Erle, A.; Bullinger, L.; Hofmann, S.; Gotz, M.; Döhner, K.; et al. Leukemic progenitor cells are susceptible to targeting by stimulated cytotoxic T cells against immunogenic leukemia-associated antigens. Int. J. Cancer. 2015, 137, 2083–2092. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Guinn, B.A.; Mohamedali, A.; Mills, K.I.; Czepulkowski, B.; Schmitt, M.; Greiner, J. Leukemia associated antigens: Their dual role as biomarkers and immunotherapeutic targets for acute myeloid leukemia. Biomark. Insights 2007, 2, 69–79. [Google Scholar] [CrossRef] [PubMed]
- Greiner, J.; Schmitt, M.; Li, L.; Giannopoulos, K.; Bosch, K.; Schmitt, A.; Döhner, K.; Schlenk, R.F.; Pollack, J.R.; Döhner, H.; et al. Expression of tumor-associated antigens in acute myeloid leukemia: Implications for specific immunotherapeutic approaches. Blood 2006, 108, 4109–4117. [Google Scholar] [CrossRef] [Green Version]
- Kern, C.H.; Yang, M.; Liu, W.S. The PRAME family of cancer testis antigens is essential for germline development and gametogenesisdagger. Biol. Reprod. 2021, 105, 290–304. [Google Scholar] [CrossRef] [PubMed]
- Xu, Y.; Zou, R.; Wang, J.; Wang, Z.W.; Zhu, X. The role of the cancer testis antigen PRAME in tumorigenesis and immunotherapy in human cancer. Cell Prolif. 2020, 53, e12770. [Google Scholar] [CrossRef] [PubMed]
- Liberante, F.G.; Pellagatti, A.; Boncheva, V.; Bowen, D.T.; Mills, K.I.; Boultwood, J.; Guinn, B.A. High and low, but not intermediate, PRAME expression levels are poor prognostic markers in myelodysplastic syndrome at disease presentation. Br. J. Haematol. 2013, 162, 282–285. [Google Scholar] [CrossRef] [PubMed]
- Qazilbash, M.H.; Wieder, E.; Thall, P.F.; Wang, X.; Rios, R.; Lu, S.; Kanodia, S.; Ruisaard, K.E.; Giralt, S.A.; Estey, E.H.; et al. PR1 peptide vaccine induces specific immunity with clinical responses in myeloid malignancies. Leukemia 2017, 31, 697–704. [Google Scholar] [CrossRef] [Green Version]
- Misra, S.; Hascall, V.C.; Markwald, R.R.; Ghatak, S. Interactions between Hyaluronan and Its Receptors (CD44, RHAMM) Regulate the Activities of Inflammation and Cancer. Front. Immunol. 2015, 6, 201. [Google Scholar] [CrossRef] [Green Version]
- Hamilton, S.R.; Fard, S.F.; Paiwand, F.F.; Tolg, C.; Veiseh, M.; Wang, C.; McCarthy, J.B.; Bissell, M.J.; Koropatnick, J.; Turley, E.A. The hyaluronan receptors CD44 and Rhamm (CD168) form complexes with ERK1,2 that sustain high basal motility in breast cancer cells. J. Biol. Chem. 2007, 282, 16667–16680. [Google Scholar] [CrossRef] [Green Version]
- Maxwell, C.A.; McCarthy, J.; Turley, E. Cell-surface and mitotic-spindle RHAMM: Moonlighting or dual oncogenic functions? J. Cell Sci. 2008, 121, 925–932. [Google Scholar] [CrossRef] [Green Version]
- Greiner, J.; Ringhoffer, M.; Taniguchi, M.; Schmitt, A.; Kirchner, D.; Krahn, G.; Heilmann, V.; Gschwend, J.; Bergmann, L.; Döhner, H.; et al. Receptor for hyaluronan acid-mediated motility (RHAMM) is a new immunogenic leukemia-associated antigen in acute and chronic myeloid leukemia. Exp. Hematol. 2002, 30, 1029–1035. [Google Scholar] [CrossRef]
- Greiner, J.; Li, L.; Ringhoffer, M.; Barth, T.F.; Giannopoulos, K.; Guillaume, P.; Ritter, G.; Wiesneth, M.; Döhner, H.; Schmitt, M. Identification and characterization of epitopes of the receptor for hyaluronic acid-mediated motility (RHAMM/CD168) recognized by CD8+ T cells of HLA-A2-positive patients with acute myeloid leukemia. Blood 2005, 106, 938–945. [Google Scholar] [CrossRef]
- Cilloni, D.; Renneville, A.; Hermitte, F.; Hills, R.K.; Daly, S.; Jovanovic, J.V.; Gottardi, E.; Fava, M.; Schnittger, S.; Weiss, T.; et al. Real-time quantitative polymerase chain reaction detection of minimal residual disease by standardized WT1 assay to enhance risk stratification in acute myeloid leukemia: A European LeukemiaNet study. J. Clin. Oncol. 2009, 27, 5195–5201. [Google Scholar] [CrossRef] [PubMed]
- Rampal, R.; Figueroa, M.E. Wilms tumor 1 mutations in the pathogenesis of acute myeloid leukemia. Haematologica 2016, 101, 672–679. [Google Scholar] [CrossRef] [Green Version]
- Luo, P.; Jing, W.; Yi, K.; Wu, S.; Zhou, F. Wilms’ tumor 1 gene in hematopoietic malignancies: Clinical implications and future directions. Leuk. Lymphoma 2020, 61, 2059–2067. [Google Scholar] [CrossRef]
- Di Stasi, A.; Jimenez, A.M.; Minagawa, K.; Al-Obaidi, M.; Rezvani, K. Review of the Results of WT1 Peptide Vaccination Strategies for Myelodysplastic Syndromes and Acute Myeloid Leukemia from Nine Different Studies. Front. Immunol. 2015, 6, 36. [Google Scholar] [CrossRef] [Green Version]
- Garg, H.; Suri, P.; Gupta, J.C.; Talwar, G.P.; Dubey, S. Survivin: A unique target for tumor therapy. Cancer Cell Int. 2016, 16, 49. [Google Scholar] [CrossRef] [Green Version]
- Greiner, J.; Brown, E.; Bullinger, L.; Hills, R.K.; Morris, V.; Döhner, H.; Mills, K.I.; Guinn, B.A. Survivin’ Acute Myeloid Leukaemia-A Personalised Target for inv(16) Patients. Int. J. Mol. Sci. 2021, 22, 10482. [Google Scholar] [CrossRef] [PubMed]
- Altieri, D.C. Survivin, cancer networks and pathway-directed drug discovery. Nat. Rev. Cancer 2008, 8, 61–70. [Google Scholar] [CrossRef] [PubMed]
- Nakahara, T.; Kita, A.; Yamanaka, K.; Mori, M.; Amino, N.; Takeuchi, M.; Tominaga, F.; Hatakeyama, S.; Kinoyama, I.; Matsuhisa, A.; et al. YM155, a novel small-molecule survivin suppressant, induces regression of established human hormone-refractory prostate tumor xenografts. Cancer Res. 2007, 67, 8014–8021. [Google Scholar] [CrossRef] [Green Version]
- Lee, A.K.; Potts, P.R. A Comprehensive Guide to the MAGE Family of Ubiquitin Ligases. J. Mol. Biol. 2017, 429, 1114–1142. [Google Scholar] [CrossRef] [Green Version]
- Florke Gee, R.R.; Chen, H.; Lee, A.K.; Daly, C.A.; Wilander, B.A.; Fon Tacer, K.; Potts, P.R. Emerging roles of the MAGE protein family in stress response pathways. J. Biol. Chem. 2020, 295, 16121–16155. [Google Scholar] [CrossRef]
- Almstedt, M.; Blagitko-Dorfs, N.; Duque-Afonso, J.; Karbach, J.; Pfeifer, D.; Jager, E.; Lubbert, M. The DNA demethylating agent 5-aza-2’-deoxycytidine induces expression of NY-ESO-1 and other cancer/testis antigens in myeloid leukemia cells. Leuk. Res. 2010, 34, 899–905. [Google Scholar] [CrossRef]
- Mussai, F.; Wheat, R.; Sarrou, E.; Booth, S.; Stavrou, V.; Fultang, L.; Perry, T.; Kearns, P.; Cheng, P.; Keeshan, K.; et al. Targeting the arginine metabolic brake enhances immunotherapy for leukaemia. Int. J. Cancer 2019, 145, 2201–2208. [Google Scholar] [CrossRef]
- Guinn, B.; Greiner, J.; Schmitt, M.; Mills, K.I. Elevated expression of the leukemia-associated antigen SSX2IP predicts survival in acute myeloid leukemia patients who lack detectable cytogenetic rearrangements. Blood 2009, 113, 1203–1204. [Google Scholar] [CrossRef]
- Davis, L.; Mills, K.I.; Orchard, K.H.; Guinn, B.A. Identification of Genes Whose Expression Overlaps Age Boundaries and Correlates with Risk Groups in Paediatric and Adult Acute Myeloid Leukaemia. Cancers 2020, 12, 2769. [Google Scholar] [CrossRef]
- Winer, E.S.; Stone, R.M. Novel therapy in Acute myeloid leukemia (AML): Moving toward targeted approaches. Ther. Adv. Hematol. 2019, 10, 2040620719860645. [Google Scholar] [CrossRef]
- Khan, G.N.; Orchard, K.; Guinn, B.A. Antigenic Targets for the Immunotherapy of Acute Myeloid Leukaemia. J. Clin. Med. 2019, 8, 134. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Schmitt, M.; Schmitt, A.; Rojewski, M.T.; Chen, J.; Giannopoulos, K.; Fei, F.; Yu, Y.; Gotz, M.; Heyduk, M.; Ritter, G.; 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, 1357–1365. [Google Scholar] [CrossRef] [PubMed]
- Greiner, J.; Schmitt, A.; Giannopoulos, K.; Rojewski, M.T.; Gotz, M.; Funk, I.; Ringhoffer, M.; Bunjes, D.; Hofmann, S.; Ritter, G.; et al. High-dose RHAMM-R3 peptide vaccination for patients with acute myeloid leukemia, myelodysplastic syndrome and multiple myeloma. Haematologica 2010, 95, 1191–1197. [Google Scholar] [CrossRef] [Green Version]
- Keilholz, U.; Letsch, A.; Busse, A.; Asemissen, A.M.; Bauer, S.; Blau, I.W.; Hofmann, W.K.; Uharek, L.; Thiel, E.; Scheibenbogen, C. A clinical and immunologic phase 2 trial of Wilms tumor gene product 1 (WT1) peptide vaccination in patients with AML and MDS. Blood 2009, 113, 6541–6548. [Google Scholar] [CrossRef] [Green Version]
- Maslak, P.G.; Dao, T.; Bernal, Y.; Chanel, S.M.; Zhang, R.; Frattini, M.; Rosenblat, T.; Jurcic, J.G.; Brentjens, R.J.; Arcila, M.E.; et al. Phase 2 trial of a multivalent WT1 peptide vaccine (galinpepimut-S) in acute myeloid leukemia. Blood Adv. 2018, 2, 224–234. [Google Scholar] [CrossRef]
- Brayer, J.; Lancet, J.E.; Powers, J.; List, A.; Balducci, L.; Komrokji, R.; Pinilla-Ibarz, J. WT1 vaccination in AML and MDS: A pilot trial with synthetic analog peptides. Am. J. Hematol. 2015, 90, 602–607. [Google Scholar] [CrossRef] [Green Version]
- Weinstock, M.; Rosenblatt, J.; Avigan, D. Dendritic Cell Therapies for Hematologic Malignancies. Mol. Ther. Methods Clin. Dev. 2017, 5, 66–75. [Google Scholar] [CrossRef] [Green Version]
- Anguille, S.; Van de Velde, A.L.; Smits, E.L.; Van Tendeloo, V.F.; Juliusson, G.; Cools, N.; Nijs, G.; Stein, B.; Lion, E.; Van Driessche, A.; et al. Dendritic cell vaccination as postremission treatment to prevent or delay relapse in acute myeloid leukemia. Blood 2017, 130, 1713–1721. [Google Scholar] [CrossRef] [Green Version]
- Van Acker, H.H.; Versteven, M.; Lichtenegger, F.S.; Roex, G.; Campillo-Davo, D.; Lion, E.; Subklewe, M.; Van Tendeloo, V.F.; Berneman, Z.N.; Anguille, S. Dendritic Cell-Based Immunotherapy of Acute Myeloid Leukemia. J. Clin. Med. 2019, 8, 579. [Google Scholar] [CrossRef] [Green Version]
- Lee, K.H.; Gowrishankar, K.; Street, J.; McGuire, H.M.; Luciani, F.; Hughes, B.; Singh, M.; Clancy, L.E.; Gottlieb, D.J.; Micklethwaite, K.P.; et al. Ex vivo enrichment of PRAME antigen-specific T cells for adoptive immunotherapy using CD137 activation marker selection. Clin. Transl. Immunol. 2020, 9, e1200. [Google Scholar] [CrossRef]
- Klobuch, S.; Hammon, K.; Vatter-Leising, S.; Neidlinger, E.; Zwerger, M.; Wandel, A.; Neuber, L.M.; Heilmeier, B.; Fichtner, R.; Mirbeth, C.; et al. HLA-DPB1 Reactive T Cell Receptors for Adoptive Immunotherapy in Allogeneic Stem Cell Transplantation. Cells 2020, 9, e1200. [Google Scholar] [CrossRef]
- ClinicalTrials.gov. Identifier: NCT03503968. TCR Modified T Cells MDG1011 in High Risk Myeloid and Lymphoid Neoplasms. Available online: https://clinicaltrials.gov/ct2/show/NCT03503968 (accessed on 8 March 2022).
- Döhner, H.; Wei, A.H.; Lowenberg, B. Towards precision medicine for AML. Nat. Rev. Clin. Oncol. 2021, 18, 577–590. [Google Scholar] [CrossRef] [PubMed]
- Daver, N.; Schlenk, R.F.; Russell, N.H.; Levis, M.J. Targeting FLT3 mutations in AML: Review of current knowledge and evidence. Leukemia 2019, 33, 299–312. [Google Scholar] [CrossRef] [Green Version]
- Döhner, K.; Thiede, C.; Jahn, N.; Panina, E.; Gambietz, A.; Larson, R.A.; Prior, T.W.; Marcucci, G.; Jones, D.; Krauter, J.; et al. Impact of NPM1/FLT3-ITD genotypes defined by the 2017 European LeukemiaNet in patients with acute myeloid leukemia. Blood 2020, 135, 371–380. [Google Scholar] [CrossRef]
- Voso, M.T.; Larson, R.A.; Jones, D.; Marcucci, G.; Prior, T.; Krauter, J.; Heuser, M.; Lavorgna, S.; Nomdedeu, J.; Geyer, S.M.; et al. Midostaurin in patients with acute myeloid leukemia and FLT3-TKD mutations: A subanalysis from the RATIFY trial. Blood Adv. 2020, 4, 4945–4954. [Google Scholar] [CrossRef]
- Graf, C.; Heidel, F.; Tenzer, S.; Radsak, M.P.; Solem, F.K.; Britten, C.M.; Huber, C.; Fischer, T.; Wolfel, T. A neoepitope generated by an FLT3 internal tandem duplication (FLT3-ITD) is recognized by leukemia-reactive autologous CD8+ T cells. Blood 2007, 109, 2985–2988. [Google Scholar] [CrossRef] [Green Version]
- Jetani, H.; Garcia-Cadenas, I.; Nerreter, T.; Thomas, S.; Rydzek, J.; Meijide, J.B.; Bonig, H.; Herr, W.; Sierra, J.; Einsele, H.; et al. CAR T-cells targeting FLT3 have potent activity against FLT3(-)ITD(+) AML and act synergistically with the FLT3-inhibitor crenolanib. Leukemia 2018, 32, 1168–1179. [Google Scholar] [CrossRef]
- Schmied, B.J.; Lutz, M.S.; Riegg, F.; Zekri, L.; Heitmann, J.S.; Buhring, H.J.; Jung, G.; Salih, H.R. Induction of NK Cell Reactivity against B-Cell Acute Lymphoblastic Leukemia by an Fc-Optimized FLT3 Antibody. Cancers 2019, 11, 1966. [Google Scholar] [CrossRef] [Green Version]
- Uckelmann, H.J.; Armstrong, S.A. Chromatin Complexes Maintain Self-Renewal of Myeloid Progenitors in AML: Opportunities for Therapeutic Intervention. Stem Cell Rep. 2020, 15, 6–12. [Google Scholar] [CrossRef]
- Stahl, M.; Menghrajani, K.; Derkach, A.; Chan, A.; Xiao, W.; Glass, J.; King, A.C.; Daniyan, A.F.; Famulare, C.; Cuello, B.M.; et al. Clinical and molecular predictors of response and survival following venetoclax therapy in relapsed/refractory AML. Blood Adv. 2021, 5, 1552–1564. [Google Scholar] [CrossRef]
- Forghieri, F.; Comoli, P.; Marasca, R.; Potenza, L.; Luppi, M. Minimal/Measurable Residual Disease Monitoring in NPM1-Mutated Acute Myeloid Leukemia: A Clinical Viewpoint and Perspectives. Int. J. Mol. Sci. 2018, 19, 3492. [Google Scholar] [CrossRef] [Green Version]
- Heuser, M.; Freeman, S.D.; Ossenkoppele, G.J.; Buccisano, F.; Hourigan, C.S.; Ngai, L.L.; Tettero, J.M.; Bachas, C.; Baer, C.; Bene, M.C.; et al. 2021 Update on MRD in acute myeloid leukemia: A consensus document from the European LeukemiaNet MRD Working Party. Blood 2021, 138, 2753–2767. [Google Scholar] [CrossRef] [PubMed]
- Schneider, V.; Zhang, L.; Bullinger, L.; Rojewski, M.; Hofmann, S.; Wiesneth, M.; Schrezenmeier, H.; Gotz, M.; Botzenhardt, U.; Barth, T.F.; et al. Leukemic stem cells of acute myeloid leukemia patients carrying NPM1 mutation are candidates for targeted immunotherapy. Leukemia 2014, 28, 1759–1762. [Google Scholar] [CrossRef] [PubMed]
- Greiner, J.; Schneider, V.; Schmitt, M.; Gotz, M.; Döhner, K.; Wiesneth, M.; Döhner, H.; Hofmann, S. 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, 1087–1088. [Google Scholar] [CrossRef]
- Van der Lee, D.I.; Reijmers, R.M.; Honders, M.W.; Hagedoorn, R.S.; de Jong, R.C.; Kester, M.G.; van der Steen, D.M.; de Ru, A.H.; Kweekel, C.; Bijen, H.M.; et al. Mutated nucleophosmin 1 as immunotherapy target in acute myeloid leukemia. J. Clin. Investig. 2019, 129, 774–785. [Google Scholar] [CrossRef]
- Narayan, R.; Olsson, N.; Wagar, L.E.; Medeiros, B.C.; Meyer, E.; Czerwinski, D.; Khodadoust, M.S.; Zhang, L.; Schultz, L.; Davis, M.M.; et al. Acute myeloid leukemia immunopeptidome reveals HLA presentation of mutated nucleophosmin. PLoS ONE 2019, 14, e0219547. [Google Scholar] [CrossRef] [Green Version]
- Greiner, J.; Ono, Y.; Hofmann, S.; Schmitt, A.; Mehring, E.; Gotz, M.; Guillaume, P.; Döhner, K.; Mytilineos, J.; Döhner, H.; et al. Mutated regions of nucleophosmin 1 elicit both CD4(+) and CD8(+) T-cell responses in patients with acute myeloid leukemia. Blood 2012, 120, 1282–1289. [Google Scholar] [CrossRef]
- Brunetti, L.; Gundry, M.C.; Sorcini, D.; Guzman, A.G.; Huang, Y.H.; Ramabadran, R.; Gionfriddo, I.; Mezzasoma, F.; Milano, F.; Nabet, B.; et al. Mutant NPM1 Maintains the Leukemic State through HOX Expression. Cancer Cell 2018, 34, 499–512.e9. [Google Scholar] [CrossRef] [Green Version]
- Baron, J.; Wang, E.S. Gemtuzumab ozogamicin for the treatment of acute myeloid leukemia. Expert Rev. Clin. Pharm. 2018, 11, 549–559. [Google Scholar] [CrossRef]
- Castaigne, S.; Pautas, C.; Terre, C.; Raffoux, E.; Bordessoule, D.; Bastie, J.N.; Legrand, O.; Thomas, X.; Turlure, P.; Reman, O.; 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, 1508–1516. [Google Scholar] [CrossRef]
- Schlenk, R.F.; Paschka, P.; Krzykalla, J.; Weber, D.; Kapp-Schwoerer, S.; Gaidzik, V.I.; Leis, C.; Fiedler, W.; Kindler, T.; Schroeder, T.; et al. Gemtuzumab Ozogamicin in NPM1-Mutated Acute Myeloid Leukemia: Early Results From the Prospective Randomized AMLSG 09-09 Phase III Study. J. Clin. Oncol. 2020, 38, 623–632. [Google Scholar] [CrossRef] [PubMed]
- Kapp-Schwoerer, S.; Weber, D.; Corbacioglu, A.; Gaidzik, V.I.; Paschka, P.; Kronke, J.; Theis, F.; Rucker, F.G.; Teleanu, M.V.; Panina, E.; et al. Impact of gemtuzumab ozogamicin on MRD and relapse risk in patients with NPM1-mutated AML: Results from the AMLSG 09-09 trial. Blood 2020, 136, 3041–3050. [Google Scholar] [CrossRef] [PubMed]
- Lane, A.A. Targeting CD123 in AML. Clin. Lymphoma Myeloma Leuk. 2020, 20 (Suppl. 1), S67–S68. [Google Scholar] [CrossRef]
- Riether, C.; Pabst, T.; Hopner, S.; Bacher, U.; Hinterbrandner, M.; Banz, Y.; Muller, R.; Manz, M.G.; Gharib, W.H.; Francisco, D.; et al. Targeting CD70 with cusatuzumab eliminates acute myeloid leukemia stem cells in patients treated with hypomethylating agents. Nat. Med. 2020, 26, 1459–1467. [Google Scholar] [CrossRef]
- Swoboda, D.M.; Sallman, D.A. The promise of macrophage directed checkpoint inhibitors in myeloid malignancies. Best Pract. Res. Clin. Haematol. 2020, 33, 101221. [Google Scholar] [CrossRef]
- Daver, N.; Konopleva, M.; Maiti, A.; Kadia, T.M.; DiNardo, C.D.; Loghavi, S.; Pemmaraju, N.; Jabbour, E.J.; Montalban-Bravo, G.; Tang, G.; et al. Phase I/II Study of Azacitidine (AZA) with Venetoclax (VEN) and Magrolimab (Magro) in Patients (pts) with Newly Diagnosed Older/Unfit or High-Risk Acute Myeloid Leukemia (AML) and Relapsed/Refractory (R/R) AML. Blood 2021, 138, 371. [Google Scholar] [CrossRef]
- Sallman, D.; Asch, A.; Kambhampati, S.; Al Malki, M.; Zeidner, J.; Donnellan, W.; Lee, D.; Vyas, P.; Jeyakumar, D.; Mannis, G.; et al. AML-196: The First-in-Class Anti-CD47 Antibody Magrolimab in Combination with Azacitidine Is Well Tolerated and Effective in AML Patients: Phase 1b Results. Clin. Lymphoma Myeloma Leuk. Abstr. 2021, 21 (Suppl. 1), S290. [Google Scholar] [CrossRef]
- Mardiana, S.; Gill, S. CAR T Cells for Acute Myeloid Leukemia: State of the Art and Future Directions. Front. Oncol. 2020, 10, 697. [Google Scholar] [CrossRef]
- Ali, S.; Kjeken, R.; Niederlaender, C.; Markey, G.; Saunders, T.S.; Opsata, M.; Moltu, K.; Bremnes, B.; Gronevik, E.; Muusse, M.; et al. The European Medicines Agency Review of Kymriah (Tisagenlecleucel) for the Treatment of Acute Lymphoblastic Leukemia and Diffuse Large B-Cell Lymphoma. Oncologist 2020, 25, e321–e327. [Google Scholar] [CrossRef] [Green Version]
- Singh, A.K.; McGuirk, J.P. CAR T cells: Continuation in a revolution of immunotherapy. Lancet Oncol. 2020, 21, e168–e178. [Google Scholar] [CrossRef]
- Freitag, F.; Maucher, M.; Riester, Z.; Hudecek, M. New targets and technologies for CAR-T cells. Curr. Opin. Oncol. 2020, 32, 510–517. [Google Scholar] [CrossRef]
- Sellner, L.; Fan, F.; Giesen, N.; Schubert, M.L.; Goldschmidt, H.; Muller-Tidow, C.; Dreger, P.; Raab, M.S.; Schmitt, M. B-cell maturation antigen-specific chimeric antigen receptor T cells for multiple myeloma: Clinical experience and future perspectives. Int. J. Cancer 2020, 147, 2029–2041. [Google Scholar] [CrossRef]
- Isidori, A.; Cerchione, C.; Daver, N.; DiNardo, C.; Garcia-Manero, G.; Konopleva, M.; Jabbour, E.; Ravandi, F.; Kadia, T.; Burguera, A.F.; et al. Immunotherapy in Acute Myeloid Leukemia: Where We Stand. Front. Oncol. 2021, 11, 656218. [Google Scholar] [CrossRef]
- Greiner, J.; Gotz, M.; Bunjes, D.; Hofmann, S.; Wais, V. Immunological and Clinical Impact of Manipulated and Unmanipulated DLI after Allogeneic Stem Cell Transplantation of AML Patients. J. Clin. Med. 2019, 9, 39. [Google Scholar] [CrossRef] [Green Version]
- Falkenburg, F.; Ruggiero, E.; Bonini, C.; Porter, D.; Miller, J.; Malard, F.; Mohty, M.; Kroger, N.; Kolb, H.J. Prevention and treatment of relapse after stem cell transplantation by cellular therapies. Bone Marrow Transplant. 2019, 54, 26–34. [Google Scholar] [CrossRef]
- Hofmann, S.; Schmitt, M.; Gotz, M.; Döhner, H.; Wiesneth, M.; Bunjes, D.; Greiner, J. Donor lymphocyte infusion leads to diversity of specific T cell responses and reduces regulatory T cell frequency in clinical responders. Int. J. Cancer 2019, 144, 1135–1146. [Google Scholar] [CrossRef]
- Hofmann, S.; Greiner, J. Immunogenic antigens as therapeutic targets against myeloid leukaemic cells. Leuk. Res. 2010, 34, 850–851. [Google Scholar] [CrossRef]
- Hofmann, S.; Greiner, J. Adoptive Immunotherapy after Allogeneic Hematopoietic Progenitor Cell Transplantation: New Perspectives for Transfusion Medicine. Transfus. Med. Hemother. 2011, 38, 173–182. [Google Scholar] [CrossRef] [Green Version]
- Lulla, P.D.; Naik, S.; Vasileiou, S.; Tzannou, I.; Watanabe, A.; Kuvalekar, M.; Lulla, S.; Carrum, G.; Ramos, C.A.; Kamble, R.; et al. Clinical effects of administering leukemia-specific donor T cells to patients with AML/MDS after allogeneic transplant. Blood 2021, 137, 2585–2597. [Google Scholar] [CrossRef]
- Al Malki, M.M.; Vasu, S.; Modi, D.; Perales, M.-A.; Bui, D.; Edavana, V.; Kim, S.; Suarez, L.; Oelke, M.; Bednárik, D.; et al. Preliminary analysis of a phase 1/2 study of NEXI-001 donor-derived multi-antigen-specific CD8+ T-cells for the treatment of relapsed acute myeloid leukemia (AML) after allogeneic hematopoietic cell transplantation (HCT). Blood 2021, 138, 4819. [Google Scholar] [CrossRef]
- Bohl, S.R.; Bullinger, L.; Rucker, F.G. Epigenetic therapy: Azacytidine and decitabine in acute myeloid leukemia. Expert Rev. Hematol. 2018, 11, 361–371. [Google Scholar] [CrossRef] [PubMed]
- Li, H.; Chiappinelli, K.B.; Guzzetta, A.A.; Easwaran, H.; Yen, R.W.; Vatapalli, R.; Topper, M.J.; Luo, J.; Connolly, R.M.; Azad, N.S.; et al. Immune regulation by low doses of the DNA methyltransferase inhibitor 5-azacitidine in common human epithelial cancers. Oncotarget 2014, 5, 587–598. [Google Scholar] [CrossRef] [PubMed]
- Daver, N.; Boddu, P.; Garcia-Manero, G.; Yadav, S.S.; Sharma, P.; Allison, J.; Kantarjian, H. Hypomethylating agents in combination with immune checkpoint inhibitors in acute myeloid leukemia and myelodysplastic syndromes. Leukemia 2018, 32, 1094–1105. [Google Scholar] [CrossRef] [PubMed]
- Ciotti, G.; Marconi, G.; Martinelli, G. Hypomethylating Agent-Based Combination Therapies to Treat Post-Hematopoietic Stem Cell Transplant Relapse of Acute Myeloid Leukemia. Front. Oncol. 2022, 11, 810387. [Google Scholar] [CrossRef]
- Daver, N.; Garcia-Manero, G.; Basu, S.; Boddu, P.C.; Alfayez, M.; Cortes, J.E.; Konopleva, M.; Ravandi-Kashani, F.; Jabbour, E.; Kadia, T.; et al. Efficacy, Safety, and Biomarkers of Response to Azacitidine and Nivolumab in Relapsed/Refractory Acute Myeloid Leukemia: A Nonrandomized, Open-Label, Phase II Study. Cancer Discov. 2019, 9, 370–383. [Google Scholar] [CrossRef] [Green Version]
- Thol, F.; Ganser, A. Treatment of Relapsed Acute Myeloid Leukemia. Curr. Treat. Options Oncol. 2020, 21, 66. [Google Scholar] [CrossRef]
- DiNardo, C.D.; Schuh, A.C.; Stein, E.M.; Montesinos, P.; Wei, A.H.; de Botton, S.; Zeidan, A.M.; Fathi, A.T.; Kantarjian, H.M.; Bennett, J.M.; et al. Enasidenib plus azacitidine versus azacitidine alone in patients with newly diagnosed, mutant-IDH2 acute myeloid leukaemia (AG221-AML-005): A single-arm, phase 1b and randomised, phase 2 trial. Lancet Oncol. 2021, 22, 1597–1608. [Google Scholar] [CrossRef]
- Wei, A.H.; Döhner, H.; Pocock, C.; Montesinos, P.; Afanasyev, B.; Dombret, H.; Ravandi, F.; Sayar, H.; Jang, J.H.; Porkka, K.; et al. Oral Azacitidine Maintenance Therapy for Acute Myeloid Leukemia in First Remission. N. Engl. J. Med. 2020, 383, 2526–2537. [Google Scholar] [CrossRef]
- Smith, B.D.; Levis, M.; Beran, M.; Giles, F.; Kantarjian, H.; Berg, K.; Murphy, K.M.; Dauses, T.; Allebach, J.; Small, D. Single-agent CEP-701, a novel FLT3 inhibitor, shows biologic and clinical activity in patients with relapsed or refractory acute myeloid leukemia. Blood 2004, 103, 3669–3676. [Google Scholar] [CrossRef]
- Smith, C.C. The growing landscape of FLT3 inhibition in AML. Educ. Program Am. Soc. Hematol. Am. Soc. Hematol. Educ. Program 2019, 2019, 539–547. [Google Scholar] [CrossRef]
- Stone, R.M.; Mandrekar, S.J.; Sanford, B.L.; Laumann, K.; Geyer, S.; Bloomfield, C.D.; Thiede, C.; Prior, T.W.; Döhner, K.; Marcucci, G.; et al. Midostaurin plus Chemotherapy for Acute Myeloid Leukemia with a FLT3 Mutation. N. Engl. J. Med. 2017, 377, 454–464. [Google Scholar] [CrossRef]
- Perl, A.E.; Martinelli, G.; Cortes, J.E.; Neubauer, A.; Berman, E.; Paolini, S.; Montesinos, P.; Baer, M.R.; Larson, R.A.; Ustun, C.; et al. Gilteritinib or Chemotherapy for Relapsed or Refractory FLT3-Mutated AML. N. Engl. J. Med. 2019, 381, 1728–1740. [Google Scholar] [CrossRef]
- Wang, E.S.; Montesinos, P.; Minden, M.D.; Lee, J.H.; Heuser, M.; Naoe, T.; Chou, W.C.; Laribi, K.; Esteve, J.; Altman, J.K.; et al. Phase 3, Open-Label, Randomized Study of Gilteritinib and Azacitidine Vs Azacitidine for Newly Diagnosed FLT3-Mutated Acute Myeloid Leukemia in Patients Ineligible for Intensive Induction Chemotherapy. Blood 2021, 138, 700. [Google Scholar] [CrossRef]
- Burchert, A.; Bug, G.; Fritz, L.V.; Finke, J.; Stelljes, M.; Rollig, C.; Wollmer, E.; Wasch, R.; Bornhauser, M.; Berg, T.; et al. Sorafenib Maintenance After Allogeneic Hematopoietic Stem Cell Transplantation for Acute Myeloid Leukemia With FLT3-Internal Tandem Duplication Mutation (SORMAIN). J. Clin. Oncol. 2020, 38, 2993–3002. [Google Scholar] [CrossRef]
- Wang, A.; Wu, H.; Chen, C.; Hu, C.; Qi, Z.; Wang, W.; Yu, K.; Liu, X.; Zou, F.; Zhao, Z.; et al. Dual inhibition of AKT/FLT3-ITD by A674563 overcomes FLT3 ligand-induced drug resistance in FLT3-ITD positive AML. Oncotarget 2016, 7, 29131–29142. [Google Scholar] [CrossRef]
- Roerden, M.; Nelde, A.; Walz, J.S. Neoantigens in Hematological Malignancies-Ultimate Targets for Immunotherapy? Front. Immunol. 2019, 10, 3004. [Google Scholar] [CrossRef] [Green Version]
- Stein, E.M.; DiNardo, C.D.; Fathi, A.T.; Mims, A.S.; Pratz, K.W.; Savona, M.R.; Stein, A.S.; Stone, R.M.; Winer, E.S.; Seet, C.S.; et al. Ivosidenib or enasidenib combined with intensive chemotherapy in patients with newly diagnosed AML: A phase 1 study. Blood 2021, 137, 1792–1803. [Google Scholar] [CrossRef]
- Cortes, J.E.; Dombret, H.; Merchant, A.; Tauchi, T.; DiRienzo, C.G.; Sleight, B.; Zhang, X.; Leip, E.P.; Shaik, N.; Bell, T.; et al. Glasdegib plus intensive/nonintensive chemotherapy in untreated acute myeloid leukemia: BRIGHT AML 1019 Phase III trials. Future Oncol. 2019, 15, 3531–3545. [Google Scholar] [CrossRef] [Green Version]
- Chan, S.M.; Thomas, D.; Corces-Zimmerman, M.R.; Xavy, S.; Rastogi, S.; Hong, W.J.; Zhao, F.; Medeiros, B.C.; Tyvoll, D.A.; Majeti, R. Isocitrate dehydrogenase 1 and 2 mutations induce BCL-2 dependence in acute myeloid leukemia. Nat. Med. 2015, 21, 178–184. [Google Scholar] [CrossRef] [Green Version]
- DiNardo, C.D.; Jonas, B.A.; Pullarkat, V.; Thirman, M.J.; Garcia, J.S.; Wei, A.H.; Konopleva, M.; Döhner, H.; Letai, A.; Fenaux, P.; et al. Azacitidine and Venetoclax in Previously Untreated Acute Myeloid Leukemia. N. Engl. J. Med. 2020, 383, 617–629. [Google Scholar] [CrossRef]
- Shahswar, R.; Beutel, G.; Klement, P.; Rehberg, A.; Gabdoulline, R.; Koenecke, C.; Markel, D.; Eggers, H.; Eder, M.; Stadler, M.; et al. FLA-IDA salvage chemotherapy combined with a seven-day course of venetoclax (FLAVIDA) in patients with relapsed/refractory acute leukaemia. Br. J. Haematol. 2020, 188, e11–e15. [Google Scholar] [CrossRef] [Green Version]
- DiNardo, C.D.; Lachowiez, C.A.; Takahashi, K.; Loghavi, S.; Xiao, L.; Kadia, T.; Daver, N.; Adeoti, M.; Short, N.J.; Sasaki, K.; et al. Venetoclax Combined With FLAG-IDA Induction and Consolidation in Newly Diagnosed and Relapsed or Refractory Acute Myeloid Leukemia. J. Clin. Oncol. 2021, 39, 2768–2778. [Google Scholar] [CrossRef] [PubMed]
- Birsen, R.; Larrue, C.; Decroocq, J.; Johnson, N.; Guiraud, N.; Gotanegre, M.; Cantero-Aguilar, L.; Grignano, E.; Huynh, T.; Fontenay, M.; et al. APR-246 induces early cell death by ferroptosis in acute myeloid leukemia. Haematologica 2021, 107, 403–416. [Google Scholar] [CrossRef] [PubMed]
- Kobayashi, T.; Makino, T.; Yamashita, K.; Saito, T.; Tanaka, K.; Takahashi, T.; Kurokawa, Y.; Yamasaki, M.; Nakajima, K.; Morii, E.; et al. APR-246 induces apoptosis and enhances chemo-sensitivity via activation of ROS and TAp73-Noxa signal in oesophageal squamous cell cancer with TP53 missense mutation. Br. J. Cancer 2021, 125, 1523–1532. [Google Scholar] [CrossRef] [PubMed]
- Wang, E.S.; Altman, J.K.; Pettit, K.M.; De Botton, S.; Walter, R.P.; Fenaux, P.; Burrows, F.; Tomkinson, B.E. Preliminary Data on a Phase 1/2A First in Human Study of the Menin-KMT2A (MLL) Inhibitor KO-539 in Patients with Relapsed or Refractory Acute Myeloid Leukemia. Blood 2020, 136, 7–8. [Google Scholar] [CrossRef]
- Tucker, N. SNDX-5613 Demonstrates Robust Clinical Activity in MLL-Rearranged and NPM1c-Mutant R/R Acute Leukemia. Targeted Oncology. 2021. Available online: https://www.targetedonc.com/view/sndx-5613-demonstrates-robust-clinical-activity-in-mll-rearranged-and-npm1c-mutant-r-r-acute-leukemia (accessed on 8 March 2022).
- Goswami, M.; Hourigan, C.S. Novel Antigen Targets for Immunotherapy of Acute Myeloid Leukemia. Curr. Drug Targets 2017, 18, 296–303. [Google Scholar] [CrossRef]
- DiNardo, C.D.; Pratz, K.; Pullarkat, V.; Jonas, B.A.; Arellano, M.; Becker, P.S.; Frankfurt, O.; Konopleva, M.; Wei, A.H.; Kantarjian, H.M.; et al. Venetoclax combined with decitabine or azacitidine in treatment-naive, elderly patients with acute myeloid leukemia. Blood 2019, 133, 7–17. [Google Scholar] [CrossRef] [Green Version]
- Morita, K.; Wang, F.; Jahn, K.; Hu, T.; Tanaka, T.; Sasaki, Y.; Kuipers, J.; Loghavi, S.; Wang, S.A.; Yan, Y.; et al. Clonal evolution of acute myeloid leukemia revealed by high-throughput single-cell genomics. Nat. Commun. 2020, 11, 5327. [Google Scholar] [CrossRef]
- Miles, L.A.; Bowman, R.L.; Merlinsky, T.R.; Csete, I.S.; Ooi, A.T.; Durruthy-Durruthy, R.; Bowman, M.; Famulare, C.; Patel, M.A.; Mendez, P.; et al. Single-cell mutation analysis of clonal evolution in myeloid malignancies. Nature 2020, 587, 477–482. [Google Scholar] [CrossRef]
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Greiner, J.; Götz, M.; Wais, V. Increasing Role of Targeted Immunotherapies in the Treatment of AML. Int. J. Mol. Sci. 2022, 23, 3304. https://0-doi-org.brum.beds.ac.uk/10.3390/ijms23063304
Greiner J, Götz M, Wais V. Increasing Role of Targeted Immunotherapies in the Treatment of AML. International Journal of Molecular Sciences. 2022; 23(6):3304. https://0-doi-org.brum.beds.ac.uk/10.3390/ijms23063304
Chicago/Turabian StyleGreiner, Jochen, Marlies Götz, and Verena Wais. 2022. "Increasing Role of Targeted Immunotherapies in the Treatment of AML" International Journal of Molecular Sciences 23, no. 6: 3304. https://0-doi-org.brum.beds.ac.uk/10.3390/ijms23063304