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Original Research

CAR-T cells dual-target CD123 and NKG2DLs to eradicate AML cells and selectively target immunosuppressive cells

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Article: 2248826 | Received 12 Mar 2023, Accepted 14 Aug 2023, Published online: 26 Aug 2023

References

  • Rollig C, Bornhäuser M, Thiede C, Taube F, Kramer M, Mohr B, Aulitzky W, Bodenstein H, Tischler H-J, Stuhlmann R, et al. Long-term prognosis of acute myeloid leukemia according to the new genetic risk classification of the European LeukemiaNet recommendations: evaluation of the proposed reporting system. J Clin Oncol. 2011;29(20):2758–12. doi:10.1200/JCO.2010.32.8500.
  • DiNardo CD, Wei AH. How I treat acute myeloid leukemia in the era of new drugs. Blood. 2020;135(2):85–96. doi:10.1182/blood.2019001239.
  • Dohner H, Estey EH, Amadori S, Appelbaum FR, Büchner T, Burnett AK, Dombret H, Fenaux P, Grimwade D, Larson RA, et al. Diagnosis and management of acute myeloid leukemia in adults: recommendations from an international expert panel, on behalf of the European LeukemiaNet. Blood. 2010;115(3):453–474. doi:10.1182/blood-2009-07-235358.
  • Lipof JJ, Loh KP, O’Dwyer K, Liesveld JL. Allogeneic hematopoietic cell transplantation for older adults with acute myeloid leukemia. Cancers Basel. 2018;10(6):179. doi:10.3390/cancers10060179.
  • Levin-Epstein R, Oliai C, Schiller G. Allogeneic hematopoietic stem cell transplantation for older patients with acute myeloid leukemia. Curr Treat Options Oncol. 2018;19(12):63. doi:10.1007/s11864-018-0577-2.
  • Sorror ML, Estey E. Allogeneic hematopoietic cell transplantation for acute myeloid leukemia in older adults. Hematology Am Soc Hematol Educ Program. 2014;2014(1):21–33. doi:10.1182/asheducation-2014.1.21.
  • Depil S, Duchateau P, Grupp SA, Mufti G, Poirot L. ‘Off-the-shelf’ allogeneic CAR T cells: development and challenges. Nat Rev Drug Discov. 2020;19(3):185–199. doi:10.1038/s41573-019-0051-2.
  • Abreu TR, Fonseca NA, Goncalves N, Moreira JN. Current challenges and emerging opportunities of CAR-T cell therapies. J Control Release. 2020;319:246–261. doi:10.1016/j.jconrel.2019.12.047.
  • Rafiq S, Hackett CS, Brentjens RJ. Engineering strategies to overcome the current roadblocks in CAR T cell therapy. Nat Rev Clin Oncol. 2020;17(3):147–167. doi:10.1038/s41571-019-0297-y.
  • Testa U, Pelosi E, Castelli G. CD123 as a therapeutic target in the treatment of hematological malignancies. Cancers Basel. 2019;11(9):1358. doi:10.3390/cancers11091358.
  • Morsink LM, Walter RB. Novel monoclonal antibody-based therapies for acute myeloid leukemia. Best Pract Res Clin Haematol. 2019;32(2):116–126. doi:10.1016/j.beha.2019.05.002.
  • Baroni ML, Sanchez Martinez D, Gutierrez Aguera F, Roca Ho H, Castella M, Zanetti S, Velasco Hernandez T, Diaz de la Guardia R, Castaño J, Anguita E, et al. 41BB-based and CD28-based CD123-redirected T-cells ablate human normal hematopoiesis in vivo. J Immunother Cancer. 2020;8(1):e000845. doi:10.1136/jitc-2020-000845.
  • Loff S, Dietrich J, Meyer J-E, Riewaldt J, Spehr J, von Bonin M, Gründer C, Swayampakula M, Franke K, Feldmann A, et al. Rapidly switchable universal CAR-T cells for treatment of CD123-positive leukemia. Mol Ther Oncolytics. 2020;17:408–420. doi:10.1016/j.omto.2020.04.009.
  • Pizzitola I, Anjos-Afonso F, Rouault-Pierre K, Lassailly F, Tettamanti S, Spinelli O, Biondi A, Biagi E, Bonnet D. Chimeric antigen receptors against CD33/CD123 antigens efficiently target primary acute myeloid leukemia cells in vivo. Leukemia. 2014;28(8):1596–1605. doi:10.1038/leu.2014.62.
  • Mardiros A, Dos Santos C, McDonald T, Brown CE, Wang X, Budde LE, Hoffman L, Aguilar B, Chang W-C, Bretzlaff W, et al. T cells expressing CD123-specific chimeric antigen receptors exhibit specific cytolytic effector functions and antitumor effects against human acute myeloid leukemia. Blood. 2013;122(18):3138–3148. doi:10.1182/blood-2012-12-474056.
  • Tettamanti S, Marin V, Pizzitola I, Magnani CF, Giordano Attianese GMP, Cribioli E, Maltese F, Galimberti S, Lopez AF, Biondi A, et al. Targeting of acute myeloid leukaemia by cytokine-induced killer cells redirected with a novel CD123-specific chimeric antigen receptor. Br J Haematol. 2013;161(3):389–401. doi:10.1111/bjh.12282.
  • You L, Han Q, Zhu L, Zhu Y, Bao C, Yang C, Lei W, Qian W. Decitabine-mediated epigenetic reprogramming enhances anti-leukemia efficacy of CD123-targeted chimeric antigen receptor T-Cells. Front Immunol. 2020;11:1787. doi:10.3389/fimmu.2020.01787.
  • Yao S, Jianlin C, Yarong L, Botao L, Qinghan W, Hongliang F, Lu Z, Hongmei N, Pin W, Hu C, et al. Donor-derived CD123-targeted CAR T cell Serves as a RIC Regimen for Haploidentical transplantation in a patient with FUS-ERG+ AML. Front Oncol. 2019;9:1358. doi:10.3389/fonc.2019.01358.
  • Budde L, Song JY, Kim Y, Blanchard S, Wagner J, Stein AS, Weng L, Del Real M, Hernandez R, Marcucci E, et al. Remissions of acute myeloid leukemia and blastic plasmacytoid dendritic cell neoplasm following treatment with CD123-specific CAR T cells: A First-in Human clinical trial. Blood. 2017;130(Suppl_1):811–811. doi:10.1182/blood.V130.Suppl_1.811.811.
  • Tasian SK, Kenderian SS, Shen F, Ruella M, Shestova O, Kozlowski M, Li Y, Schrank-Hacker A, Morrissette JJD, Carroll M, et al. Optimized depletion of chimeric antigen receptor T cells in murine xenograft models of human acute myeloid leukemia. Blood. 2017;129(17):2395–2407. doi:10.1182/blood-2016-08-736041.
  • Cummins KD, Frey N, Nelson AM, Schmidt A, Luger S, Isaacs RE, Lacey SF, Hexner E, Melenhorst JJ, June CH et al. Treating Relapsed/Refractory (RR) AML with biodegradable anti-CD123 CAR modified T cells. Blood. 2017;130:1359.
  • Baragano Raneros A, Martín-Palanco V, Fernandez AF, Rodriguez RM, Fraga MF, Lopez-Larrea C, Suarez-Alvarez B. Methylation of NKG2D ligands contributes to immune system evasion in acute myeloid leukemia. Genes Immun. 2015;16(1):71–82. doi:10.1038/gene.2014.58.
  • Soriani A, Fionda C, Ricci B, Iannitto ML, Cippitelli M, Santoni A. Chemotherapy-elicited upregulation of NKG2D and DNAM-1 ligands as a therapeutic target in multiple myeloma. Oncoimmunology. 2013;2(12):e26663. doi:10.4161/onci.26663.
  • Baumeister SH, Murad J, Werner L, Daley H, Trebeden-Negre H, Gicobi JK, Schmucker A, Reder J, Sentman CL, Gilham DE, et al. Phase I trial of Autologous CAR T cells targeting NKG2D ligands in patients with AML/MDS and multiple myeloma. Cancer Immunol Res. 2019;7(1):100–112. doi:10.1158/2326-6066.CIR-18-0307.
  • Sallman DA, Brayer JB, Poire X, Havelange V, Awada A, Lewalle P, Odunsi K, Wang ES, Lonez C, Lequertier T, et al. Results from the completed dose-escalation of the hematological arm of the phase I think study evaluating multiple infusions of NKG2D-Based CAR T-Cells as Standalone therapy in relapse/Refractory acute myeloid leukemia and myelodysplastic syndrome patients. Blood. 2019;134(Supplement_1):3826–3826. doi:10.1182/blood-2019-128020.
  • Deeren D, Maertens JA, Lin T, Beguin Y, Demoulin B, Fontaine M, Sotiropoulou PA, Alcantar-Orozco E, Breman E, Dheur M-S, et al. First results from the dose escalation segment of the phase i clinical study evaluating cyad-02, an optimized non gene-edited engineered NKG2D CAR T-Cell product, in relapsed or refractory acute myeloid leukemia and myelodysplastic syndrome patients. Blood. 2020;136(Supplement 1):36–36. doi:10.1182/blood-2020-139667.
  • Bachier C, Borthakur G, Hosing C, Blum W, Rotta M, Ojeras P, Barnett B, Rajangam K, Majhail NS, Nikiforow S, et al. A phase 1 study of NKX101, an Allogeneic CAR Natural killer (NK) cell therapy, in Subjects with Relapsed/Refractory (R/R) acute myeloid leukemia (AML) or higher-Risk Myelodysplastic Syndrome (MDS). Blood. 2020;136(Supplement 1):42–43. doi:10.1182/blood-2020-134625.
  • Rahma OE, Hodi FS. The Intersection between tumor angiogenesis and immune suppression. Clin Cancer Res. 2019;25(18):5449–5457. doi:10.1158/1078-0432.CCR-18-1543.
  • Dysthe M, Parihar R. Myeloid-derived suppressor cells in the tumor microenvironment. Adv Exp Med Biol. 2020;1224:117–140. doi:10.1007/978-3-030-35723-8_8.
  • Zamarron BF, Chen W. Dual roles of immune cells and their factors in cancer development and progression. Int J Biol Sci. 2011;7(5):651–658. doi:10.7150/ijbs.7.651.
  • Wang L, Jia B, Claxton DF, Ehmann WC, Rybka WB, Mineishi S, Naik S, Khawaja MR, Sivik J, Han J, et al. VISTA is highly expressed on MDSCs and mediates an inhibition of T cell response in patients with AML. Oncoimmunology. 2018;7(9):e1469594. doi:10.1080/2162402X.2018.1469594.
  • Pyzer AR, Stroopinsky D, Rajabi H, Washington A, Tagde A, Coll M, Fung J, Bryant MP, Cole L, Palmer K, et al. MUC1-mediated induction of myeloid-derived suppressor cells in patients with acute myeloid leukemia. Blood. 2017;129(13):1791–1801. doi:10.1182/blood-2016-07-730614.
  • Parihar R, Rivas C, Huynh M, Omer B, Lapteva N, Metelitsa LS, Gottschalk SM, Rooney CM. NK cells expressing a chimeric activating receptor eliminate MDSCs and rescue impaired CAR-T cell activity against solid tumors. Cancer Immunol Res. 2019;7(3):363–375. doi:10.1158/2326-6066.CIR-18-0572.
  • Ruella M, Klichinsky M, Kenderian SS, Shestova O, Ziober A, Kraft DO, Feldman M, Wasik MA, June CH, Gill S, et al. Overcoming the immunosuppressive tumor microenvironment of Hodgkin lymphoma using chimeric antigen receptor T cells. Cancer Discov. 2017;7(10):1154–1167. doi:10.1158/2159-8290.CD-16-0850.
  • Willier S, Rothämel P, Hastreiter M, Wilhelm J, Stenger D, Blaeschke F, Rohlfs M, Kaeuferle T, Schmid I, Albert MH, et al. CLEC12A and CD33 coexpression as a preferential target for pediatric AML combinatorial immunotherapy. Blood. 2021;137(8):1037–1049. doi:10.1182/blood.2020006921.
  • Zah E, Lin MY, Silva-Benedict A, Jensen MC, Chen YY. T cells expressing CD19/CD20 Bispecific chimeric antigen receptors Prevent antigen escape by Malignant B cells. Cancer Immunol Res. 2016;4(6):498–508. doi:10.1158/2326-6066.CIR-15-0231.
  • Schneider D, Xiong Y, Wu D, Nӧlle V, Schmitz S, Haso W, Kaiser A, Dropulic B, Orentas RJ. A tandem CD19/CD20 CAR lentiviral vector drives on-target and off-target antigen modulation in leukemia cell lines. J Immunother Cancer. 2017;5(1):42. doi:10.1186/s40425-017-0246-1.
  • Qin H, Ramakrishna S, Nguyen S, Fountaine TJ, Ponduri A, Stetler-Stevenson M, Yuan CM, Haso W, Shern JF, Shah NN, et al. Preclinical development of Bivalent chimeric antigen receptors targeting both CD19 and CD22. Mol Ther Oncolytics. 2018;11:127–137. doi:10.1016/j.omto.2018.10.006.
  • Hua J, Qian W, Wu X, Zhou L, Yu L, Chen S, Zhang J, Qiu H. sequential Infusion of anti-CD22 and anti-CD19 chimeric antigen receptor T cells for a pediatric Ph-like B-ALL patient that relapsed after CART-Cell and Haplo-HSCT therapy: A case report and review of literature. Onco Targets Ther. 2020;13:2311–2317. doi:10.2147/OTT.S235882.
  • Gill SI. How close are we to CAR T-cell therapy for AML? Best Pract Res Clin Haematol. Best Pract Res Clin Haematol. 2019;32(4):101104. doi:10.1016/j.beha.2019.101104.
  • Philip B, Kokalaki E, Mekkaoui L, Thomas S, Straathof K, Flutter B, Marin V, Marafioti T, Chakraverty R, Linch D, et al. A highly compact epitope-based marker/suicide gene for easier and safer T-cell therapy. Blood. 2014;124(8):1277–1287. doi:10.1182/blood-2014-01-545020.
  • Nowbakht P, Ionescu MCS, Rohner A, Kalberer CP, Rossy E, Mori L, Cosman D, De Libero G, Wodnar-Filipowicz A. Ligands for natural killer cell–activating receptors are expressed upon the maturation of normal myelomonocytic cells but at low levels in acute myeloid leukemias. Blood. 2005;105(9):3615–3622. doi:10.1182/blood-2004-07-2585.
  • Hinrichs CS, Borman ZA, Gattinoni L, Yu Z, Burns WR, Huang J, Klebanoff CA, Johnson LA, Kerkar SP, Yang S, et al. Human effector CD8+ T cells derived from naive rather than memory subsets possess superior traits for adoptive immunotherapy. Blood. 2011;117(3):808–814. doi:10.1182/blood-2010-05-286286.
  • Kawalekar OU, O’ Connor RS, Fraietta JA, Guo L, McGettigan SE, Posey AD, Patel PR, Guedan S, Scholler J, Keith B, et al. Distinct signaling of coreceptors regulates specific metabolism pathways and impacts memory development in CAR T cells. Immunity. 2016;44(3):712–712. doi:10.1016/j.immuni.2016.02.023.
  • Gargett T, Truong N, Ebert LM, Yu WB, Brown MP. Optimization of manufacturing conditions for chimeric antigen receptor T cells to favor cells with a central memory phenotype. Cytotherapy. 2019;21(6):593–602. doi:10.1016/j.jcyt.2019.03.003.
  • Gill S, Tasian SK, Ruella M, Shestova O, Li Y, Porter DL, Carroll M, Danet-Desnoyers G, Scholler J, Grupp SA, et al. Preclinical targeting of human acute myeloid leukemia and myeloablation using chimeric antigen receptor–modified T cells. Blood. 2014;123(15):2343–2354. doi:10.1182/blood-2013-09-529537.
  • Cummins KD, Gill S. Will CAR T cell therapy have a role in AML? Promises and pitfalls. Semin Hematol. 2019;56(2):155–163. doi:10.1053/j.seminhematol.2018.08.008.
  • Shao R, Li Z, Xin H, Jiang S, Zhu Y, Liu J, Huang R, Xu K, Shi X. Biomarkers as targets for CAR-T/NK cell therapy in AML. Biomark Res. 2023;11(1):65. doi:10.1186/s40364-023-00501-9.
  • Atilla E, Benabdellah K. The black Hole: CAR T cell therapy in AML. Cancers Basel. 2023;15(10):2713. doi:10.3390/cancers15102713.
  • Grada Z, Hegde M, Byrd T, Shaffer DR, Ghazi A, Brawley VS, Corder A, Schönfeld K, Koch J, Dotti G, et al. TanCAR: A novel bispecific chimeric antigen receptor for cancer immunotherapy. Mol Ther Nucleic Acids. 2013;2:e105. doi:10.1038/mtna.2013.32.
  • Hegde M, Corder A, Chow KK, Mukherjee M, Ashoori A, Kew Y, Zhang YJ, Baskin DS, Merchant FA, Brawley VS, et al. Combinational targeting offsets antigen escape and enhances effector functions of adoptively transferred T cells in glioblastoma. Mol Ther. 2013;21(11):2087–2101. doi:10.1038/mt.2013.185.
  • Hegde M, Mukherjee M, Grada Z, Pignata A, Landi D, Navai SA, Wakefield A, Fousek K, Bielamowicz K, Chow KKH, et al. Tandem CAR T cells targeting HER2 and IL13Rα2 mitigate tumor antigen escape. J Clin Invest. 2016;126(8):3036–3052. doi:10.1172/JCI83416.
  • Zanetti SR, Velasco-Hernandez T, Gutierrez-Agüera F, Díaz VM, Romecín PA, Roca-Ho H, Sánchez-Martínez D, Tirado N, Baroni ML, Petazzi P, et al. A novel and efficient tandem CD19- and CD22-directed CAR for B cell ALL. Mol Ther. 2022;30(2):550–563. doi:10.1016/j.ymthe.2021.08.033.
  • Qasim W, Zhan H, Samarasinghe S, Adams S, Amrolia P, Stafford S, Butler K, Rivat C, Wright G, Somana K, et al. Molecular remission of infant B-ALL after infusion of universal TALEN gene-edited CAR T cells. Sci Transl Med. 2017;9(374). doi:10.1126/scitranslmed.aaj2013.
  • Hu Y, Zhou Y, Zhang M, Ge W, Li Y, Yang L, Wei G, Han L, Wang H, Yu S, et al. CRISPR/Cas9-engineered universal CD19/CD22 dual-targeted CAR-T cell therapy for relapsed/refractory B-cell acute lymphoblastic leukemia. Clin Cancer Res. 2021;27(10):2764–2772. doi:10.1158/1078-0432.CCR-20-3863.
  • Dupouy S, Marchiq I, Derippe T, Almena-Carrasco M, Jozwik A, Fouliard S, Adimy Y, Geronimi J, Graham C, Jain N, et al. Clinical pharmacology and determinants of response to UCART19, an Allogeneic anti-CD19 CAR-T cell product, in adult B-cell acute lymphoblastic leukemia. Cancer Res Commun. 2022;2(11):1520–1531. doi:10.1158/2767-9764.CRC-22-0175.