{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,1,16]],"date-time":"2026-01-16T17:22:56Z","timestamp":1768584176707,"version":"3.49.0"},"reference-count":219,"publisher":"MDPI AG","issue":"12","license":[{"start":{"date-parts":[[2020,12,3]],"date-time":"2020-12-03T00:00:00Z","timestamp":1606953600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Cancers"],"abstract":"<jats:p>Despite the availability of an increasing number of targeted therapeutics and wider use of allogeneic hematopoietic stem cell transplantation, many patients with acute myeloid leukemia (AML) ultimately succumb to this disease. Given their remarkable efficacy in B-acute lymphoblastic leukemia and other CD19-expressing B cell malignancies, there is hope adoptive cellular transfer, particularly chimeric antigen receptor (CAR)-modified immune effector cell (IEC) therapies, may afford a novel, potent immune-based approach for the treatment of AML that complements or replaces existing ones and improves cure rates. However, it is unclear how best to translate the success of these therapies from B cell malignancies, where use of highly potent immunotherapies is facilitated by identified target antigens with near ubiquitous expression on malignant cells and non-fatal consequences from \u201con-target, off-tumor cell\u201d toxicities. Herein, we review the current status of CAR-modified IEC therapies for AML, with considerations regarding suitable, relatively leukemia-restricted target antigens, expected toxicities, and interactions of the engineered cells with a profoundly immunosuppressive tumor microenvironment that restricts their therapeutic efficacy. With these challenges in mind, we will discuss possible strategies to improve the cells\u2019 potency as well as their therapeutic window for optimal clinical use in AML.<\/jats:p>","DOI":"10.3390\/cancers12123617","type":"journal-article","created":{"date-parts":[[2020,12,3]],"date-time":"2020-12-03T20:09:40Z","timestamp":1607026180000},"page":"3617","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":12,"title":["Chimeric Antigen Receptor (CAR)-Modified Immune Effector Cell Therapy for Acute Myeloid Leukemia (AML)"],"prefix":"10.3390","volume":"12","author":[{"given":"Utkarsh H.","family":"Acharya","sequence":"first","affiliation":[{"name":"Divisions of Hematologic Malignancies &amp; Immune Effector Cell Therapy, Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, MA 02215, USA"},{"name":"Department of Medicine, Harvard Medical School, Boston, MA 02215, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9268-3341","authenticated-orcid":false,"given":"Roland B.","family":"Walter","sequence":"additional","affiliation":[{"name":"Clinical Research Division, Fred Hutchinson Cancer Research Center, Seattle, WA 98109, USA"},{"name":"Department of Medicine, Division of Hematology, University of Washington, Seattle, WA 98195, USA"},{"name":"Department of Laboratory Medicine &amp; Pathology, University of Washington, Seattle, WA 98195, USA"},{"name":"Department of Epidemiology, University of Washington, Seattle, WA 98195, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2020,12,3]]},"reference":[{"key":"ref_1","first-page":"485","article-title":"Cytosine arabinoside (NSC-63878) and daunorubicin (NSC-83142) therapy in acute nonlymphocytic leukemia","volume":"57","author":"Yates","year":"1973","journal-title":"Cancer Chemother. Rep."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"362","DOI":"10.1182\/blood-2017-12-778472","article-title":"Treatment strategies for adolescent and young adult patients with acute myeloid leukemia","volume":"132","author":"Freyer","year":"2018","journal-title":"Blood"},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"57","DOI":"10.1097\/MOP.0000000000000855","article-title":"Pediatric acute myeloid leukemia: Updates on biology, risk stratification, and therapy","volume":"32","author":"Elgarten","year":"2020","journal-title":"Curr. Opin. Pediatr."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"S5","DOI":"10.5045\/br.2020.S002","article-title":"Treatments for children and adolescents with AML","volume":"55","author":"Kim","year":"2020","journal-title":"Blood Res."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"1136","DOI":"10.1056\/NEJMra1406184","article-title":"Acute myeloid leukemia","volume":"373","author":"Weisdorf","year":"2015","journal-title":"N. Engl. J. Med."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"424","DOI":"10.1182\/blood-2016-08-733196","article-title":"Diagnosis and management of AML in adults: 2017 ELN recommendations from an international expert panel","volume":"129","author":"Estey","year":"2017","journal-title":"Blood"},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"1251","DOI":"10.1007\/s40265-017-0779-0","article-title":"Midostaurin: First global approval","volume":"77","author":"Kim","year":"2017","journal-title":"Drugs"},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"1705","DOI":"10.1007\/s40265-017-0813-2","article-title":"Enasidenib: First global approval","volume":"77","author":"Kim","year":"2017","journal-title":"Drugs"},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"3242","DOI":"10.1158\/1078-0432.CCR-17-3179","article-title":"FDA approval: Gemtuzumab ozogamicin for the treatment of adults with newly diagnosed CD33-positive acute myeloid leukemia","volume":"24","author":"Jen","year":"2018","journal-title":"Clin. Cancer Res."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"1103","DOI":"10.1634\/theoncologist.2017-0604","article-title":"FDA approval summary: Mylotarg for treatment of patients with relapsed or refractory CD33-positive acute myeloid leukemia","volume":"23","author":"Norsworthy","year":"2018","journal-title":"Oncologist"},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"2685","DOI":"10.1158\/1078-0432.CCR-18-2990","article-title":"FDA approval summary: (daunorubicin and cytarabine) liposome for injection for the treatment of adults with high-risk acute myeloid leukemia","volume":"25","author":"Krauss","year":"2019","journal-title":"Clin. Cancer Res."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"3205","DOI":"10.1158\/1078-0432.CCR-18-3749","article-title":"FDA approval summary: Ivosidenib for relapsed or refractory acute myeloid leukemia with an isocitrate dehydrogenase-1 mutation","volume":"25","author":"Norsworthy","year":"2019","journal-title":"Clin. Cancer Res."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"6021","DOI":"10.1158\/1078-0432.CCR-19-0365","article-title":"FDA approval summary: Glasdegib for newly diagnosed acute myeloid leukemia","volume":"25","author":"Norsworthy","year":"2019","journal-title":"Clin. Cancer Res."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"331","DOI":"10.1007\/s40265-019-1062-3","article-title":"Gilteritinib: First global approval","volume":"79","author":"Dhillon","year":"2019","journal-title":"Drugs"},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"617","DOI":"10.1056\/NEJMoa2012971","article-title":"Azacitidine and venetoclax in previously untreated acute myeloid leukemia","volume":"383","author":"DiNardo","year":"2020","journal-title":"N. Engl. J. Med."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"2137","DOI":"10.1182\/blood.2020004856","article-title":"Venetoclax plus LDAC for newly diagnosed AML ineligible for intensive chemotherapy: A phase 3 randomized placebo-controlled trial","volume":"135","author":"Wei","year":"2020","journal-title":"Blood"},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"439","DOI":"10.1056\/NEJMoa1709866","article-title":"Tisagenlecleucel in children and young adults with B-cell lymphoblastic leukemia","volume":"378","author":"Maude","year":"2018","journal-title":"N. Engl. J. Med."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"2531","DOI":"10.1056\/NEJMoa1707447","article-title":"Axicabtagene ciloleucel CAR T-cell therapy in refractory large B-cell lymphoma","volume":"377","author":"Neelapu","year":"2017","journal-title":"N. Engl. J. Med."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"1331","DOI":"10.1056\/NEJMoa1914347","article-title":"KTE-X19 CAR T-cell therapy in relapsed or refractory mantle-cell lymphoma","volume":"382","author":"Wang","year":"2020","journal-title":"N. Engl. J. Med."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"269","DOI":"10.1038\/nri3191","article-title":"Adoptive immunotherapy for cancer: Harnessing the T cell response","volume":"12","author":"Restifo","year":"2012","journal-title":"Nat. Rev. Immunol."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"280","DOI":"10.1126\/scitranslmed.aaa3643","article-title":"Adoptive cellular therapy: A race to the finish line","volume":"7","author":"June","year":"2015","journal-title":"Sci. Transl. Med."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"62","DOI":"10.1126\/science.aaa4967","article-title":"Adoptive cell transfer as personalized immunotherapy for human cancer","volume":"348","author":"Rosenberg","year":"2015","journal-title":"Science"},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"113","DOI":"10.1016\/j.coph.2015.08.006","article-title":"Cancer gene therapy with T cell receptors and chimeric antigen receptors","volume":"24","author":"Stauss","year":"2015","journal-title":"Curr. Opin. Pharmacol."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"220","DOI":"10.1016\/j.tips.2015.11.004","article-title":"Adoptive T cell therapies: A comparison of T cell receptors and chimeric antigen receptors","volume":"37","author":"Harris","year":"2016","journal-title":"Trends Pharmacol. Sci."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"145","DOI":"10.1146\/annurev-immunol-042718-041407","article-title":"Emerging cellular therapies for cancer","volume":"37","author":"Guedan","year":"2019","journal-title":"Ann. Rev. Immunol."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"520","DOI":"10.1038\/leu.2017.226","article-title":"Cord blood NK cells engineered to express IL-15 and a CD19-targeted CAR show long-term persistence and potent antitumor activity","volume":"32","author":"Liu","year":"2018","journal-title":"Leukemia"},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"545","DOI":"10.1056\/NEJMoa1910607","article-title":"Use of CAR-transduced natural killer cells in CD19-positive lymphoid tumors","volume":"382","author":"Liu","year":"2020","journal-title":"N. Engl. J. Med."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"179","DOI":"10.1097\/PPO.0000000000000378","article-title":"T-cell receptor-based immunotherapy for hematologic malignancies","volume":"25","author":"Biernacki","year":"2019","journal-title":"Cancer J."},{"key":"ref_29","doi-asserted-by":"crossref","unstructured":"Gaissmaier, L., Elshiaty, M., and Christopoulos, P. (2020). Breaking bottlenecks for the TCR therapy of cancer. Cells, 9.","DOI":"10.3390\/cells9092095"},{"key":"ref_30","doi-asserted-by":"crossref","unstructured":"Manfredi, F., Cianciotti, B.C., Potenza, A., Tassi, E., Noviello, M., Biondi, A., Ciceri, F., Bonini, C., and Ruggiero, E. (2020). TCR redirected T cells for cancer treatment: Achievements, hurdles, and goals. Front. Immunol., 11.","DOI":"10.3389\/fimmu.2020.01689"},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"1064","DOI":"10.1038\/s41591-019-0472-9","article-title":"T cell receptor gene therapy targeting WT1 prevents acute myeloid leukemia relapse post-transplant","volume":"25","author":"Chapuis","year":"2019","journal-title":"Nat. Med."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"1361","DOI":"10.1126\/science.aar6711","article-title":"CAR T cell immunotherapy for human cancer","volume":"359","author":"June","year":"2018","journal-title":"Science"},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"64","DOI":"10.1056\/NEJMra1706169","article-title":"Chimeric antigen receptor therapy","volume":"379","author":"June","year":"2018","journal-title":"N. Engl. J. Med."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"95","DOI":"10.1002\/hon.2591","article-title":"CAR T-cell therapy: Full speed ahead","volume":"37","author":"Sermer","year":"2019","journal-title":"Hematol. Oncol."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"647","DOI":"10.1007\/s40259-019-00384-z","article-title":"CAR-T engineering: Optimizing signal transduction and effector mechanisms","volume":"33","author":"Roselli","year":"2019","journal-title":"BioDrugs"},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"200","DOI":"10.1038\/s41573-019-0052-1","article-title":"NK cells for cancer immunotherapy","volume":"19","author":"Shimasaki","year":"2020","journal-title":"Nat. Rev. Drug Discov."},{"key":"ref_37","doi-asserted-by":"crossref","unstructured":"Myers, J.A., and Miller, J.S. (2020). Exploring the NK cell platform for cancer immunotherapy. Nat. Rev. Clin. Oncol.","DOI":"10.1038\/s41571-020-0426-7"},{"key":"ref_38","doi-asserted-by":"crossref","unstructured":"Bachiller, M., Battram, A.M., Perez-Amill, L., and Mart\u00edn-Antonio, B. (2020). Natural killer cells in immunotherapy: Are we nearly there?. Cancers, 12.","DOI":"10.3390\/cancers12113139"},{"key":"ref_39","doi-asserted-by":"crossref","unstructured":"Mehta, R.S., and Rezvani, K. (2018). Chimeric antigen receptor expressing natural killer cells for the immunotherapy of cancer. Front. Immunol., 9.","DOI":"10.3389\/fimmu.2018.00283"},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"1255","DOI":"10.1016\/j.leukres.2008.11.024","article-title":"Transfection with mRNA for CD19 specific chimeric antigen receptor restores NK cell mediated killing of CLL cells","volume":"33","author":"Boissel","year":"2009","journal-title":"Leuk. Res."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"4857","DOI":"10.1158\/1078-0432.CCR-08-2810","article-title":"2B4 (CD244) signaling by recombinant antigen-specific chimeric receptors costimulates natural killer cell activation to leukemia and neuroblastoma cells","volume":"15","author":"Altvater","year":"2009","journal-title":"Clin. Cancer Res."},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"958","DOI":"10.3109\/10428194.2011.634048","article-title":"Comparison of mRNA and lentiviral based transfection of natural killer cells with chimeric antigen receptors recognizing lymphoid antigens","volume":"53","author":"Boissel","year":"2012","journal-title":"Leuk. Lymphoma"},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"824","DOI":"10.1089\/hum.2012.202","article-title":"Modification of hematopoietic stem\/progenitor cells with CD19-specific chimeric antigen receptors as a novel approach for cancer immunotherapy","volume":"24","author":"Ryan","year":"2013","journal-title":"Hum. Gene Ther."},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"e26527","DOI":"10.4161\/onci.26527","article-title":"Retargeting NK-92 cells by means of CD19- and CD20-specific chimeric antigen receptors compares favorably with antibody-dependent cellular cytotoxicity","volume":"2","author":"Boissel","year":"2013","journal-title":"Oncoimmunology"},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"83","DOI":"10.1007\/s00109-015-1327-6","article-title":"Efficient generation of gene-modified human natural killer cells via alpharetroviral vectors","volume":"94","author":"Suerth","year":"2016","journal-title":"J. Mol. Med."},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"1287","DOI":"10.1111\/jcmm.12810","article-title":"CD19-CAR engineered NK-92 cells are sufficient to overcome NK cell resistance in B-cell malignancies","volume":"20","author":"Romanski","year":"2016","journal-title":"J. Cell Mol. Med."},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"1799","DOI":"10.1002\/ijc.30217","article-title":"Chimeric antigen receptor-engineered cytokine-induced killer cells overcome treatment resistance of pre-B-cell acute lymphoblastic leukemia and enhance survival","volume":"139","author":"Oelsner","year":"2016","journal-title":"Int. J. Cancer"},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"467","DOI":"10.1158\/2326-6066.CIR-17-0207","article-title":"Intrinsic functional potential of NK-cell subsets constrains retargeting driven by chimeric antigen receptors","volume":"6","author":"Oei","year":"2018","journal-title":"Cancer Immunol. Res."},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"596","DOI":"10.1016\/j.ccell.2018.08.017","article-title":"Enhanced anti-lymphoma activity of CAR19-iNKT cells underpinned by dual CD19 and CD1d targeting","volume":"34","author":"Rotolo","year":"2018","journal-title":"Cancer Cell"},{"key":"ref_50","doi-asserted-by":"crossref","unstructured":"Bari, R., Granzin, M., Tsang, K.S., Roy, A., Krueger, W., Orentas, R., Schneider, D., Pfeifer, R., Moeker, N., and Verhoeyen, E. (2019). A distinct subset of highly proliferative and lentiviral vector (LV)-transducible NK cells define a readily engineered subset for adoptive cellular therapy. Front. Immunol., 10.","DOI":"10.3389\/fimmu.2019.02784"},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"5108","DOI":"10.1172\/JCI126350","article-title":"Chimeric antigen receptor-induced BCL11B suppression propagates NK-like cell development","volume":"129","author":"Maluski","year":"2019","journal-title":"J. Clin. Invest."},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"1102","DOI":"10.1038\/s41375-019-0613-7","article-title":"Efficacy of third-party chimeric antigen receptor modified peripheral blood natural killer cells for adoptive cell therapy of B-cell precursor acute lymphoblastic leukemia","volume":"34","author":"Quintarelli","year":"2020","journal-title":"Leukemia"},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"1291","DOI":"10.1038\/s41375-019-0663-x","article-title":"Interaction kinetics with transcriptomic and secretory responses of CD19-CAR natural killer-cell therapy in CD20 resistant non-hodgkin lymphoma","volume":"34","author":"Ravi","year":"2020","journal-title":"Leukemia"},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"2308","DOI":"10.1182\/blood.2020006619","article-title":"CAR-modified memory-like NK cells exhibit potent responses to NK-resistant lymphomas","volume":"136","author":"Gang","year":"2020","journal-title":"Blood"},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"e108","DOI":"10.1002\/cpim.108","article-title":"Purification, culture, and CD19-CAR lentiviral transduction of adult and umbilical cord blood NK cells","volume":"131","author":"Herrera","year":"2020","journal-title":"Curr. Protoc. Immunol."},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"2186","DOI":"10.1038\/leu.2012.145","article-title":"Leukemia-associated antigens and their relevance to the immunotherapy of acute myeloid leukemia","volume":"26","author":"Anguille","year":"2012","journal-title":"Leukemia"},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"506","DOI":"10.1016\/j.ccell.2017.09.004","article-title":"Integrating proteomics and transcriptomics for systematic combinatorial chimeric antigen receptor therapy of AML","volume":"32","author":"Perna","year":"2017","journal-title":"Cancer Cell"},{"key":"ref_58","doi-asserted-by":"crossref","first-page":"116","DOI":"10.1016\/j.beha.2019.05.002","article-title":"Novel monoclonal antibody-based therapies for acute myeloid leukemia","volume":"32","author":"Morsink","year":"2019","journal-title":"Best Pract. Res. Clin. Haematol."},{"key":"ref_59","doi-asserted-by":"crossref","unstructured":"Testa, U., Pelosi, E., and Castelli, G. (2019). CD123 as a therapeutic target in the treatment of hematological malignancies. Cancers, 11.","DOI":"10.3390\/cancers11091358"},{"key":"ref_60","doi-asserted-by":"crossref","first-page":"389","DOI":"10.1111\/bjh.12282","article-title":"Targeting of acute myeloid leukaemia by cytokine-induced killer cells redirected with a novel CD123-specific chimeric antigen receptor","volume":"161","author":"Tettamanti","year":"2013","journal-title":"Br. J. Haematol."},{"key":"ref_61","doi-asserted-by":"crossref","first-page":"3138","DOI":"10.1182\/blood-2012-12-474056","article-title":"T cells expressing CD123-specific chimeric antigen receptors exhibit specific cytolytic effector functions and antitumor effects against human acute myeloid leukemia","volume":"122","author":"Mardiros","year":"2013","journal-title":"Blood"},{"key":"ref_62","doi-asserted-by":"crossref","first-page":"1596","DOI":"10.1038\/leu.2014.62","article-title":"Chimeric antigen receptors against CD33\/CD123 antigens efficiently target primary acute myeloid leukemia cells in vivo","volume":"28","author":"Pizzitola","year":"2014","journal-title":"Leukemia"},{"key":"ref_63","doi-asserted-by":"crossref","first-page":"408","DOI":"10.1016\/j.omto.2020.04.009","article-title":"Rapidly switchable universal CAR-T cells for treatment of CD123-positive leukemia","volume":"17","author":"Loff","year":"2020","journal-title":"Mol. Ther. Oncol."},{"key":"ref_64","doi-asserted-by":"crossref","unstructured":"Baroni, M.L., Sanchez Martinez, D., Gutierrez Aguera, F., Roca Ho, H., Castella, M., Zanetti, S.R., Velasco Hernandez, T., Diaz de la Guardia, R., Casta\u00f1o, J., and Anguita, E. (2020). 41BB-based and CD28-based CD123-redirected T-cells ablate human normal hematopoiesis in vivo. J. Immunother. Cancer, 8.","DOI":"10.1136\/jitc-2020-000845"},{"key":"ref_65","doi-asserted-by":"crossref","unstructured":"You, L., Han, Q., Zhu, L., Zhu, Y., Bao, C., Yang, C., Lei, W., and Qian, W. (2020). Decitabine-mediated epigenetic reprograming enhances anti-leukemia efficacy of CD123-targeted chimeric antigen receptor T-cells. Front. Immunol., 11.","DOI":"10.3389\/fimmu.2020.01787"},{"key":"ref_66","doi-asserted-by":"crossref","unstructured":"Yao, S., Jianlin, C., Yarong, L., Botao, L., Qinghan, W., Hongliang, F., Lu, Z., Hongmei, N., Pin, W., and Hu, C. (2019). Donor-derived CD123-targeted CAR T cell serves as a RIC regimen for haploidentical transplantation in a patient with FUS-ERG+ AML. Front. Oncol., 9.","DOI":"10.3389\/fonc.2019.01358"},{"key":"ref_67","doi-asserted-by":"crossref","first-page":"811","DOI":"10.1182\/blood.V130.Suppl_1.811.811","article-title":"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","volume":"130","author":"Budde","year":"2017","journal-title":"Blood"},{"key":"ref_68","doi-asserted-by":"crossref","first-page":"2395","DOI":"10.1182\/blood-2016-08-736041","article-title":"Optimized depletion of chimeric antigen receptor T cells in murine xenograft models of human acute myeloid leukemia","volume":"129","author":"Tasian","year":"2017","journal-title":"Blood"},{"key":"ref_69","first-page":"1359","article-title":"Treating relapsed\/refractory (RR) AML with biodegradable anti-CD123 CAR modified T cells","volume":"130","author":"Cummins","year":"2017","journal-title":"Blood"},{"key":"ref_70","doi-asserted-by":"crossref","first-page":"6198","DOI":"10.1182\/blood-2011-11-325050","article-title":"Acute myeloid leukemia stem cells and CD33-targeted immunotherapy","volume":"119","author":"Walter","year":"2012","journal-title":"Blood"},{"key":"ref_71","doi-asserted-by":"crossref","first-page":"143","DOI":"10.1016\/j.blre.2014.04.001","article-title":"The past and future of CD33 as therapeutic target in acute myeloid leukemia","volume":"28","author":"Laszlo","year":"2014","journal-title":"Blood Rev."},{"key":"ref_72","doi-asserted-by":"crossref","first-page":"339","DOI":"10.1080\/13543784.2018.1452911","article-title":"Investigational CD33-targeted therapeutics for acute myeloid leukemia","volume":"27","author":"Walter","year":"2018","journal-title":"Expert Opin. Investig. Drugs"},{"key":"ref_73","unstructured":"Walter, R.B. (2020). Brief overview of antibody-drug conjugate therapy for acute leukemia. Expert Opin. Biol. Ther., 1\u20135."},{"key":"ref_74","doi-asserted-by":"crossref","first-page":"1855","DOI":"10.1038\/leu.2017.187","article-title":"Gemtuzumab ozogamicin in acute myeloid leukemia","volume":"31","author":"Godwin","year":"2017","journal-title":"Leukemia"},{"key":"ref_75","doi-asserted-by":"crossref","first-page":"955","DOI":"10.1080\/14712598.2020.1788540","article-title":"Expanding use of CD33-directed immunotherapy","volume":"20","author":"Walter","year":"2020","journal-title":"Expert Opin. Biol. Ther."},{"key":"ref_76","doi-asserted-by":"crossref","unstructured":"Dutour, A., Marin, V., Pizzitola, I., Valsesia-Wittmann, S., Lee, D., Yvon, E., Finney, H., Lawson, A., Brenner, M., and Biondi, A. (2012). In vitro and In vivo antitumor effect of anti-CD33 chimeric receptor-expressing EBV-CTL against CD33 acute myeloid leukemia. Adv. Hematol., 2012.","DOI":"10.1155\/2012\/683065"},{"key":"ref_77","doi-asserted-by":"crossref","first-page":"1637","DOI":"10.1038\/leu.2015.52","article-title":"CD33-specific chimeric antigen receptor T cells exhibit potent preclinical activity against human acute myeloid leukemia","volume":"29","author":"Kenderian","year":"2015","journal-title":"Leukemia"},{"key":"ref_78","doi-asserted-by":"crossref","first-page":"626","DOI":"10.1089\/hum.2017.241","article-title":"CD33-specific chimeric antigen receptor T cells with different co-stimulators showed potent anti-leukemia efficacy and different phenotype","volume":"29","author":"Li","year":"2018","journal-title":"Hum. Gene Ther."},{"key":"ref_79","doi-asserted-by":"crossref","first-page":"184","DOI":"10.1038\/mt.2014.164","article-title":"Treatment of CD33-directed chimeric antigen receptor-modified T cells in one patient with relapsed and refractory acute myeloid leukemia","volume":"23","author":"Wang","year":"2015","journal-title":"Mol. Ther."},{"key":"ref_80","first-page":"1083","article-title":"First-in-man clinical trial of CAR NK-92 cells: Safety test of CD33-CAR NK-92 cells in patients with relapsed and refractory acute myeloid leukemia","volume":"8","author":"Tang","year":"2018","journal-title":"Am. J. Cancer Res."},{"key":"ref_81","doi-asserted-by":"crossref","first-page":"3","DOI":"10.1182\/blood-2020-142494","article-title":"CD33 targeting primary CAR-NK cells generated by CRISPR mediated gene insertion show enhanced anti-AML activity","volume":"136","author":"Kararoudi","year":"2020","journal-title":"Blood"},{"key":"ref_82","doi-asserted-by":"crossref","first-page":"1974","DOI":"10.1016\/j.ymthe.2020.05.021","article-title":"Targeting CD33 in chemoresistant AML patient-derived xenografts by CAR-CIK cells modified with an improved SB transposon system","volume":"28","author":"Rotiroti","year":"2020","journal-title":"Mol. Ther."},{"key":"ref_83","doi-asserted-by":"crossref","first-page":"26","DOI":"10.1016\/j.blre.2018.10.003","article-title":"Prognostic and therapeutic role of CLEC12A in acute myeloid leukemia","volume":"34","author":"Morsink","year":"2019","journal-title":"Blood Rev."},{"key":"ref_84","doi-asserted-by":"crossref","first-page":"41","DOI":"10.1186\/s13045-019-0726-5","article-title":"Targeting CLL-1 for acute myeloid leukemia therapy","volume":"12","author":"Ma","year":"2019","journal-title":"J. Hematol. Oncol."},{"key":"ref_85","doi-asserted-by":"crossref","first-page":"2202","DOI":"10.1016\/j.ymthe.2017.05.024","article-title":"Treatment of acute myeloid leukemia with T cells expressing chimeric antigen receptors directed to C-type lectin-like molecule 1","volume":"25","author":"Tashiro","year":"2017","journal-title":"Mol. Ther."},{"key":"ref_86","doi-asserted-by":"crossref","unstructured":"Laborda, E., Mazagova, M., Shao, S., Wang, X., Quirino, H., Woods, A.K., Hampton, E.N., Rodgers, D.T., Kim, C.H., and Schultz, P.G. (2017). Development of a chimeric antigen receptor targeting C-type lectin-like molecule-1 for human acute myeloid leukemia. Int. J. Mol. Sci., 18.","DOI":"10.3390\/ijms18112259"},{"key":"ref_87","doi-asserted-by":"crossref","first-page":"7","DOI":"10.1186\/s13045-017-0553-5","article-title":"CAR-T cells targeting CLL-1 as an approach to treat acute myeloid leukemia","volume":"11","author":"Wang","year":"2018","journal-title":"J. Hematol. Oncol."},{"key":"ref_88","doi-asserted-by":"crossref","first-page":"13","DOI":"10.1182\/blood-2020-140648","article-title":"Phase I clinical trial of autologous CLL1 CAR-T therapy for pediatric patients with relapsed and refractory acute myeloid leukemia","volume":"136","author":"Bu","year":"2020","journal-title":"Blood"},{"key":"ref_89","first-page":"8","article-title":"NKG2D ligands as therapeutic targets","volume":"13","author":"Spear","year":"2013","journal-title":"Cancer Immun. Arch."},{"key":"ref_90","doi-asserted-by":"crossref","first-page":"100","DOI":"10.1158\/2326-6066.CIR-18-0307","article-title":"Phase I trial of autologous CAR T cells targeting NKG2D ligands in patients with AML\/MDS and multiple myeloma","volume":"7","author":"Baumeister","year":"2019","journal-title":"Cancer Immunol. Res."},{"key":"ref_91","doi-asserted-by":"crossref","first-page":"3826","DOI":"10.1182\/blood-2019-128020","article-title":"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","volume":"134","author":"Sallman","year":"2019","journal-title":"Blood"},{"key":"ref_92","doi-asserted-by":"crossref","first-page":"36","DOI":"10.1182\/blood-2020-139667","article-title":"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","volume":"136","author":"Deeren","year":"2020","journal-title":"Blood"},{"key":"ref_93","doi-asserted-by":"crossref","first-page":"42","DOI":"10.1182\/blood-2020-134625","article-title":"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)","volume":"136","author":"Bachier","year":"2020","journal-title":"Blood"},{"key":"ref_94","doi-asserted-by":"crossref","first-page":"71","DOI":"10.1038\/gene.2014.58","article-title":"Methylation of NKG2D ligands contributes to immune system evasion in acute myeloid leukemia","volume":"16","author":"Fernandez","year":"2015","journal-title":"Genes Immun."},{"key":"ref_95","doi-asserted-by":"crossref","first-page":"678","DOI":"10.1038\/gt.2010.21","article-title":"Gene-modified T cells as immunotherapy for multiple myeloma and acute myeloid leukemia expressing the Lewis Y antigen","volume":"17","author":"Peinert","year":"2010","journal-title":"Gene Ther."},{"key":"ref_96","doi-asserted-by":"crossref","first-page":"2122","DOI":"10.1038\/mt.2013.154","article-title":"Persistence and efficacy of second generation CAR T cell against the LeY antigen in acute myeloid leukemia","volume":"21","author":"Ritchie","year":"2013","journal-title":"Mol. Ther."},{"key":"ref_97","doi-asserted-by":"crossref","first-page":"3401","DOI":"10.1182\/blood.V91.9.3401","article-title":"A strong expression of CD44-6v correlates with shorter survival of patients with acute myeloid leukemia","volume":"91","author":"Legras","year":"1998","journal-title":"Blood"},{"key":"ref_98","doi-asserted-by":"crossref","first-page":"593","DOI":"10.1038\/sj.bmt.1700940","article-title":"Expression of CD44 isoforms by highly enriched CD34-positive cells in cord blood, bone marrow and leukaphereses","volume":"20","author":"Neu","year":"1997","journal-title":"Bone Marrow Transplant."},{"key":"ref_99","doi-asserted-by":"crossref","first-page":"3461","DOI":"10.1182\/blood-2013-04-493361","article-title":"CD44v6-targeted T cells mediate potent antitumor effects against acute myeloid leukemia and multiple myeloma","volume":"122","author":"Casucci","year":"2013","journal-title":"Blood"},{"key":"ref_100","doi-asserted-by":"crossref","first-page":"1532","DOI":"10.1182\/blood-2002-02-0492","article-title":"The roles of FLT3 in hematopoiesis and leukemia","volume":"100","author":"Gilliland","year":"2002","journal-title":"Blood"},{"key":"ref_101","doi-asserted-by":"crossref","first-page":"1072","DOI":"10.1182\/blood.V128.22.1072.1072","article-title":"Preclinical development of FLT3-redirected chimeric antigen receptor T cell immunotherapy for acute myeloid leukemia","volume":"128","author":"Chien","year":"2016","journal-title":"Blood"},{"key":"ref_102","doi-asserted-by":"crossref","first-page":"60","DOI":"10.1186\/s13045-018-0603-7","article-title":"Targeting FLT3 in acute myeloid leukemia using ligand-based chimeric antigen receptor-engineered T cells","volume":"11","author":"Wang","year":"2018","journal-title":"J. Hematol. Oncol."},{"key":"ref_103","doi-asserted-by":"crossref","first-page":"4","DOI":"10.1182\/blood-2020-142745","article-title":"Preclinical development of anti-FLT3 CAR-T therapy for the treatment of acute myeloid leukemia","volume":"136","author":"Shrestha","year":"2020","journal-title":"Blood"},{"key":"ref_104","doi-asserted-by":"crossref","first-page":"2237","DOI":"10.1016\/j.ymthe.2020.06.022","article-title":"Allogeneic FLT3 CAR T cells with an off-switch exhibit potent activity against AML and can be depleted to expedite bone marrow recovery","volume":"28","author":"Sommer","year":"2020","journal-title":"Mol. Ther."},{"key":"ref_105","doi-asserted-by":"crossref","first-page":"1168","DOI":"10.1038\/s41375-018-0009-0","article-title":"CAR T-cells targeting FLT3 have potent activity against FLT3(-)ITD(+) AML and act synergistically with the FLT3-inhibitor crenolanib","volume":"32","author":"Jetani","year":"2018","journal-title":"Leukemia"},{"key":"ref_106","first-page":"993","article-title":"Flow cytometric characterization of acute myeloid leukemia: IV. Comparison to the differentiation pathway of normal hematopoietic progenitor cells","volume":"6","author":"Terstappen","year":"1992","journal-title":"Leukemia"},{"key":"ref_107","doi-asserted-by":"crossref","first-page":"e116","DOI":"10.1038\/cti.2016.73","article-title":"All-trans retinoic acid enhances cytotoxic effect of T cells with an anti-CD38 chimeric antigen receptor in acute myeloid leukemia","volume":"5","author":"Yoshida","year":"2016","journal-title":"Clin. Transl. Immunol."},{"key":"ref_108","doi-asserted-by":"crossref","first-page":"34","DOI":"10.1182\/blood-2020-141602","article-title":"CD38-directed CAR-T cell therapy: A novel immunotherapy strategy for relapsed acute myeloid leukemia after allogeneic hematopoietic stem cell transplantation","volume":"136","author":"Tang","year":"2020","journal-title":"Blood"},{"key":"ref_109","doi-asserted-by":"crossref","first-page":"4408","DOI":"10.7150\/jca.28952","article-title":"Preclinical targeting of human acute myeloid leukemia using CD4-specific chimeric antigen receptor (CAR) T cells and NK cells","volume":"10","author":"Salman","year":"2019","journal-title":"J. Cancer"},{"key":"ref_110","doi-asserted-by":"crossref","first-page":"272","DOI":"10.1016\/j.ymthe.2018.10.001","article-title":"CD7 CAR T cells for the therapy of acute myeloid leukemia","volume":"27","author":"Atilla","year":"2019","journal-title":"Mol. Ther."},{"key":"ref_111","first-page":"35","article-title":"CXCR4-expressing anti-CD25 CAR T-cells effectively eliminate human AML cells in vivo","volume":"136","author":"Saito","year":"2020","journal-title":"Blood"},{"key":"ref_112","doi-asserted-by":"crossref","first-page":"23","DOI":"10.1182\/blood-2020-142161","article-title":"Investigation of ALLO-316: A fratricide-resistant allogeneic CAR T targeting CD70 as a potential therapy for the treatment of AML","volume":"136","author":"Srinivasan","year":"2020","journal-title":"Blood"},{"key":"ref_113","doi-asserted-by":"crossref","first-page":"2688","DOI":"10.1038\/s41375-020-0818-9","article-title":"Anti-human CD117 CAR T-cells efficiently eliminate healthy and malignant CD117-expressing hematopoietic cells","volume":"34","author":"Myburgh","year":"2020","journal-title":"Leukemia"},{"key":"ref_114","doi-asserted-by":"crossref","first-page":"180","DOI":"10.1016\/j.omto.2020.03.019","article-title":"B7-H3-targeted CAR-T cells exhibit potent antitumor effects on hematologic and solid tumors","volume":"17","author":"Zhang","year":"2020","journal-title":"Mol. Ther. Oncol."},{"key":"ref_115","doi-asserted-by":"crossref","first-page":"3466","DOI":"10.1182\/blood-2014-11-612721","article-title":"Targeting of folate receptor beta on acute myeloid leukemia blasts with chimeric antigen receptor-expressing T cells","volume":"125","author":"Lynn","year":"2015","journal-title":"Blood"},{"key":"ref_116","doi-asserted-by":"crossref","first-page":"1355","DOI":"10.1038\/leu.2016.35","article-title":"High-affinity FRbeta-specific CAR T cells eradicate AML and normal myeloid lineage without HSC toxicity","volume":"30","author":"Lynn","year":"2016","journal-title":"Leukemia"},{"key":"ref_117","doi-asserted-by":"crossref","first-page":"12","DOI":"10.1182\/blood-2020-141671","article-title":"GRP78 Is expressed on the cell surface of pediatric AML blasts and can be targeted with GRP78-CAR T cells without toxicity to hematopoietic progenitor cells","volume":"136","author":"Hebbar","year":"2020","journal-title":"Blood"},{"key":"ref_118","doi-asserted-by":"crossref","first-page":"2487","DOI":"10.1016\/j.ymthe.2018.08.001","article-title":"A novel anti-LILRB4 CAR-T cell for the treatment of monocytic AML","volume":"26","author":"John","year":"2018","journal-title":"Mol. Ther."},{"key":"ref_119","doi-asserted-by":"crossref","first-page":"11","DOI":"10.1182\/blood-2020-143140","article-title":"Therapeutic targeting of mesothelin in acute myeloid leukemia with chimeric antigen receptor T cell therapy","volume":"136","author":"Le","year":"2020","journal-title":"Blood"},{"key":"ref_120","doi-asserted-by":"crossref","first-page":"e1147","DOI":"10.1002\/cti2.1147","article-title":"Development and characterisation of NKp44-based chimeric antigen receptors that confer T cells with NK cell-like specificity","volume":"9","author":"Kasahara","year":"2020","journal-title":"Clin. Transl. Immunol."},{"key":"ref_121","doi-asserted-by":"crossref","first-page":"51","DOI":"10.1182\/blood-2020-136860","article-title":"CRISPR-Cas9 knock out of CD5 enhances the anti-tumor activity of chimeric antigen receptor T cells","volume":"136","author":"Chun","year":"2020","journal-title":"Blood"},{"key":"ref_122","doi-asserted-by":"crossref","first-page":"847","DOI":"10.1038\/nbt.4195","article-title":"Targeted delivery of a PD-1-blocking scFv by CAR-T cells enhances anti-tumor efficacy in vivo","volume":"36","author":"Rafiq","year":"2018","journal-title":"Nat. Biotechnol."},{"key":"ref_123","doi-asserted-by":"crossref","first-page":"713","DOI":"10.1182\/blood.2019002779","article-title":"Bispecific and split CAR T cells targeting CD13 and TIM3 eradicate acute myeloid leukemia","volume":"135","author":"He","year":"2020","journal-title":"Blood"},{"key":"ref_124","doi-asserted-by":"crossref","first-page":"554","DOI":"10.1007\/s11684-017-0543-6","article-title":"CRISPR-Cas9 mediated LAG-3 disruption in CAR-T cells","volume":"11","author":"Zhang","year":"2017","journal-title":"Front. Med."},{"key":"ref_125","doi-asserted-by":"crossref","first-page":"1680","DOI":"10.1182\/blood-2018-99-116745","article-title":"Efficacy and toxicity of JCAR014 in combination with durvalumab for the treatment of patients with relapsed\/refractory aggressive B-cell non-Hodgkin lymphoma","volume":"132","author":"Hirayama","year":"2018","journal-title":"Blood"},{"key":"ref_126","doi-asserted-by":"crossref","first-page":"S173","DOI":"10.1016\/j.bbmt.2018.12.314","article-title":"End of phase 1 results from Zuma-6: Axicabtagene ciloleucel (Axi-Cel) in combination with atezolizumab for the treatment of patients with refractory diffuse large B cell lymphoma","volume":"25","author":"Jacobson","year":"2019","journal-title":"Biol. Blood Marrow Transplant."},{"key":"ref_127","doi-asserted-by":"crossref","first-page":"25","DOI":"10.1182\/blood-2020-142013","article-title":"Single and dual targeting chimeric antigen receptor T-cell therapy in acute myeloid leukemia","volume":"136","author":"Chitre","year":"2020","journal-title":"Blood"},{"key":"ref_128","doi-asserted-by":"crossref","first-page":"22","DOI":"10.1182\/blood-2020-141540","article-title":"Combinatorial antigen targeting strategy for acute myeloid leukemia","volume":"136","author":"Atilla","year":"2020","journal-title":"Blood"},{"key":"ref_129","doi-asserted-by":"crossref","first-page":"30","DOI":"10.1182\/blood-2020-140092","article-title":"Repurposing bi-specific chimeric antigen receptor (CAR) approach to enhance CAR T cell activity against low antigen density tumors","volume":"136","author":"Mardiana","year":"2020","journal-title":"Blood"},{"key":"ref_130","doi-asserted-by":"crossref","first-page":"64","DOI":"10.1038\/s41375-018-0180-3","article-title":"Coexpression profile of leukemic stem cell markers for combinatorial targeted therapy in AML","volume":"33","author":"Haubner","year":"2019","journal-title":"Leukemia"},{"key":"ref_131","doi-asserted-by":"crossref","first-page":"8443","DOI":"10.1158\/0008-5472.CAN-04-1659","article-title":"C-type lectin-like molecule-1: A novel myeloid cell surface marker associated with acute myeloid leukemia","volume":"64","author":"Bakker","year":"2004","journal-title":"Cancer Res."},{"key":"ref_132","doi-asserted-by":"crossref","unstructured":"Willier, S., Roth\u00e4mel, P., Hastreiter, M., Wilhelm, J., Stenger, D., Blaeschke, F., Rohlfs, M., Kaeuferle, T., Schmid, I., and Albert, M.H. (2020). CLEC12A and CD33 co-expression as preferential target on pediatric AML for combinatorial immunotherapy. Blood.","DOI":"10.1182\/blood.2020006921"},{"key":"ref_133","doi-asserted-by":"crossref","first-page":"901","DOI":"10.1182\/blood-2018-99-110579","article-title":"First-in-human CLL1-CD33 compound CAR T cell therapy induces complete remission in patients with refractory acute myeloid leukemia: Update on phase 1 clinical trial","volume":"132","author":"Liu","year":"2018","journal-title":"Blood"},{"key":"ref_134","first-page":"27","article-title":"First-in-human CLL1-CD33 compound CAR (cCAR) T cell therapy in relapsed and refractory acute myeloid leukemia","volume":"4","author":"Liu","year":"2020","journal-title":"Hemasphere"},{"key":"ref_135","doi-asserted-by":"crossref","first-page":"10","DOI":"10.1182\/blood-2020-141214","article-title":"Nanobody based tri-specific chimeric antigen receptor to treat acute myeloid leukaemia","volume":"136","author":"Hazelton","year":"2020","journal-title":"Blood"},{"key":"ref_136","doi-asserted-by":"crossref","first-page":"1135","DOI":"10.1158\/1078-0432.CCR-13-0956","article-title":"A genome-wide aberrant RNA splicing in patients with acute myeloid leukemia identifies novel potential disease markers and therapeutic targets","volume":"20","author":"Adamia","year":"2014","journal-title":"Clin. Cancer Res."},{"key":"ref_137","doi-asserted-by":"crossref","first-page":"985","DOI":"10.1016\/j.jcyt.2016.05.001","article-title":"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","volume":"18","author":"Ma","year":"2016","journal-title":"Cytotherapy"},{"key":"ref_138","doi-asserted-by":"crossref","first-page":"1788","DOI":"10.1038\/leu.2016.373","article-title":"Optimized T-cell receptor-mimic chimeric antigen receptor T cells directed toward the intracellular Wilms Tumor 1 antigen","volume":"31","author":"Rafiq","year":"2017","journal-title":"Leukemia"},{"key":"ref_139","doi-asserted-by":"crossref","unstructured":"Xie, G., Ivica, N.A., Jia, B., Li, Y., Dong, H., Liang, Y., Brown, D., Rizwan, R., and Chen, J. (2020). CAR-T cells targeting a nucleophosmin neoepitope exhibit potent specific activity in mouse models of acute myeloid leukaemia. Nat. Biomed. Eng.","DOI":"10.1038\/s41551-020-00625-5"},{"key":"ref_140","doi-asserted-by":"crossref","first-page":"5904","DOI":"10.1038\/onc.2008.271","article-title":"The tumor microenvironment and its role in promoting tumor growth","volume":"27","author":"Whiteside","year":"2008","journal-title":"Oncogene"},{"key":"ref_141","doi-asserted-by":"crossref","first-page":"128","DOI":"10.3389\/fimmu.2019.00128","article-title":"CAR T cells for solid tumors: New strategies for finding, infiltrating, and surviving in the tumor microenvironment","volume":"10","author":"Martinez","year":"2019","journal-title":"Front. Immunol."},{"key":"ref_142","doi-asserted-by":"crossref","first-page":"1216","DOI":"10.3324\/haematol.2016.143180","article-title":"Acute myeloid leukemia cells polarize macrophages towards a leukemia supporting state in a Growth factor independence 1 dependent manner","volume":"101","author":"Botezatu","year":"2016","journal-title":"Haematologica"},{"key":"ref_143","doi-asserted-by":"crossref","first-page":"579","DOI":"10.1007\/s12185-015-1865-2","article-title":"Increase in myeloid-derived suppressor cells (MDSCs) associated with minimal residual disease (MRD) detection in adult acute myeloid leukemia","volume":"102","author":"Sun","year":"2015","journal-title":"Int. J. Hematol."},{"key":"ref_144","doi-asserted-by":"crossref","first-page":"e1469594","DOI":"10.1080\/2162402X.2018.1469594","article-title":"VISTA is highly expressed on MDSCs and mediates an inhibition of T cell response in patients with AML","volume":"7","author":"Wang","year":"2018","journal-title":"Oncoimmunology"},{"key":"ref_145","doi-asserted-by":"crossref","first-page":"262","DOI":"10.3389\/fonc.2020.00262","article-title":"A bump in the road: How the hostile AML microenvironment affects CAR T cell therapy","volume":"10","author":"Epperly","year":"2020","journal-title":"Front. Oncol."},{"key":"ref_146","doi-asserted-by":"crossref","first-page":"2019","DOI":"10.1038\/leu.2012.87","article-title":"Natural killer cell immune escape in acute myeloid leukemia","volume":"26","author":"Lion","year":"2012","journal-title":"Leukemia"},{"key":"ref_147","doi-asserted-by":"crossref","first-page":"4233","DOI":"10.1182\/blood-2007-07-099226","article-title":"Identification of discrete tumor-induced myeloid-derived suppressor cell subpopulations with distinct T cell-suppressive activity","volume":"111","author":"Movahedi","year":"2008","journal-title":"Blood"},{"key":"ref_148","doi-asserted-by":"crossref","first-page":"817","DOI":"10.1007\/s00262-015-1692-6","article-title":"Liver myeloid-derived suppressor cells expand in response to liver metastases in mice and inhibit the anti-tumor efficacy of anti-CEA CAR-T","volume":"64","author":"Burga","year":"2015","journal-title":"Cancer Immunol. Immunother."},{"key":"ref_149","doi-asserted-by":"crossref","first-page":"869","DOI":"10.1158\/2326-6066.CIR-15-0230","article-title":"Reduction of MDSCs with all-trans retinoic acid improves CAR therapy efficacy for sarcomas","volume":"4","author":"Long","year":"2016","journal-title":"Cancer Immunol. Res."},{"key":"ref_150","doi-asserted-by":"crossref","first-page":"3793","DOI":"10.1182\/blood-2009-03-208181","article-title":"Depletion of endogenous tumor-associated regulatory T cells improves the efficacy of adoptive cytotoxic T-cell immunotherapy in murine acute myeloid leukemia","volume":"114","author":"Zhou","year":"2009","journal-title":"Blood"},{"key":"ref_151","doi-asserted-by":"crossref","first-page":"6995","DOI":"10.1158\/1078-0432.CCR-19-0101","article-title":"Clinical efficacy and tumor microenvironment influence in a dose-escalation study of anti-CD19 chimeric antigen receptor T cells in refractory B-cell non-Hodgkin\u2019s lymphoma","volume":"25","author":"Yan","year":"2019","journal-title":"Clin. Cancer Res."},{"key":"ref_152","doi-asserted-by":"crossref","first-page":"6796","DOI":"10.1158\/0008-5472.CAN-14-0079","article-title":"Efficacy of CAR T-cell therapy in large tumors relies upon stromal targeting by IFNgamma","volume":"74","author":"Textor","year":"2014","journal-title":"Cancer Res."},{"key":"ref_153","doi-asserted-by":"crossref","unstructured":"Han, Y., Dong, Y., Yang, Q., Xu, W., Jiang, S., Yu, Z., Yu, K., and Zhang, S. (2018). Acute myeloid leukemia cells express ICOS ligand to promote the expansion of regulatory T cells. Front. Immunol., 9.","DOI":"10.3389\/fimmu.2018.02227"},{"key":"ref_154","doi-asserted-by":"crossref","first-page":"1855","DOI":"10.1016\/j.ymthe.2018.05.003","article-title":"Dominant-negative TGF-beta receptor enhances PSMA-targeted human CAR T cell proliferation and augments prostate cancer eradication","volume":"26","author":"Kloss","year":"2018","journal-title":"Mol. Ther."},{"key":"ref_155","doi-asserted-by":"crossref","unstructured":"Morgan, M.A., and Schambach, A. (2018). Engineering CAR-T cells for improved function against solid tumors. Front. Immunol., 9.","DOI":"10.3389\/fimmu.2018.02493"},{"key":"ref_156","doi-asserted-by":"crossref","first-page":"208","DOI":"10.1016\/j.imlet.2012.02.014","article-title":"Identification of microRNA transcriptome involved in human natural killer cell activation","volume":"143","author":"Liu","year":"2012","journal-title":"Immunol. Lett."},{"key":"ref_157","doi-asserted-by":"crossref","first-page":"6392","DOI":"10.1182\/blood-2009-03-209650","article-title":"T lymphocytes coexpressing CCR4 and a chimeric antigen receptor targeting CD30 have improved homing and antitumor activity in a Hodgkin tumor model","volume":"113","author":"Rooney","year":"2009","journal-title":"Blood"},{"key":"ref_158","doi-asserted-by":"crossref","first-page":"346","DOI":"10.1038\/nbt.4086","article-title":"IL-7 and CCL19 expression in CAR-T cells improves immune cell infiltration and CAR-T cell survival in the tumor","volume":"36","author":"Adachi","year":"2018","journal-title":"Nat. Biotechnol."},{"key":"ref_159","doi-asserted-by":"crossref","first-page":"1876","DOI":"10.1182\/blood-2018-11-887067","article-title":"The response to lymphodepletion impacts PFS in patients with aggressive non-Hodgkin lymphoma treated with CD19 CAR T cells","volume":"133","author":"Hirayama","year":"2019","journal-title":"Blood"},{"key":"ref_160","doi-asserted-by":"crossref","unstructured":"Barsoumian, H.B., Yolcu, E.S., and Shirwan, H. (2016). 4-1BB signaling in conventional T cells drives IL-2 production that overcomes CD4+CD25+FoxP3+ T regulatory cell suppression. PLoS ONE, 11.","DOI":"10.1371\/journal.pone.0153088"},{"key":"ref_161","doi-asserted-by":"crossref","first-page":"571","DOI":"10.1158\/2326-6066.CIR-16-0376","article-title":"Transgenic expression of IL15 improves antiglioma activity of IL13Ralpha2-CAR T cells but results in antigen loss variants","volume":"5","author":"Krenciute","year":"2017","journal-title":"Cancer Immunol. Res."},{"key":"ref_162","doi-asserted-by":"crossref","unstructured":"Teague, R.M., and Kline, J. (2013). Immune evasion in acute myeloid leukemia: Current concepts and future directions. J. Immunother. Cancer, 1.","DOI":"10.1186\/2051-1426-1-13"},{"key":"ref_163","doi-asserted-by":"crossref","first-page":"2871","DOI":"10.1182\/blood-2006-07-036863","article-title":"Modulation of tryptophan catabolism by human leukemic cells results in the conversion of CD25\u2212 into CD25+ T regulatory cells","volume":"109","author":"Curti","year":"2007","journal-title":"Blood"},{"key":"ref_164","doi-asserted-by":"crossref","first-page":"326","DOI":"10.1016\/0003-9861(91)90142-6","article-title":"1-Methyl-DL-tryptophan, beta-(3-benzofuranyl)-DL-alanine (the oxygen analog of tryptophan), and beta-[3-benzo(b)thienyl]-DL-alanine (the sulfur analog of tryptophan) are competitive inhibitors for indoleamine 2,3-dioxygenase","volume":"291","author":"Cady","year":"1991","journal-title":"Arch. Biochem. Biophys."},{"key":"ref_165","doi-asserted-by":"crossref","first-page":"270","DOI":"10.1007\/s12032-010-9459-6","article-title":"Expression of indoleamine 2,3-dioxygenase in acute myeloid leukemia and the effect of its inhibition on cultured leukemia blast cells","volume":"28","author":"Sallam","year":"2011","journal-title":"Med. Oncol."},{"key":"ref_166","doi-asserted-by":"crossref","first-page":"3905","DOI":"10.1182\/blood-2015-01-621474","article-title":"Tumor indoleamine 2,3-dioxygenase (IDO) inhibits CD19-CAR T cells and is downregulated by lymphodepleting drugs","volume":"125","author":"Ninomiya","year":"2015","journal-title":"Blood"},{"key":"ref_167","doi-asserted-by":"crossref","first-page":"3737","DOI":"10.1111\/cas.13827","article-title":"Reinforce the antitumor activity of CD8(+) T cells via glutamine restriction","volume":"109","author":"Nabe","year":"2018","journal-title":"Cancer Sci."},{"key":"ref_168","doi-asserted-by":"crossref","first-page":"3521","DOI":"10.1182\/blood-2013-03-493163","article-title":"Inhibiting glutamine uptake represents an attractive new strategy for treating acute myeloid leukemia","volume":"122","author":"Willems","year":"2013","journal-title":"Blood"},{"key":"ref_169","doi-asserted-by":"crossref","first-page":"749","DOI":"10.1182\/blood-2013-01-480129","article-title":"Acute myeloid leukemia creates an arginase-dependent immunosuppressive microenvironment","volume":"122","author":"Mussai","year":"2013","journal-title":"Blood"},{"key":"ref_170","doi-asserted-by":"crossref","first-page":"2201","DOI":"10.1002\/ijc.32028","article-title":"Targeting the arginine metabolic brake enhances immunotherapy for leukaemia","volume":"145","author":"Mussai","year":"2019","journal-title":"Int. J. Cancer"},{"key":"ref_171","doi-asserted-by":"crossref","first-page":"929","DOI":"10.1172\/JCI89455","article-title":"Targeting the adenosine 2A receptor enhances chimeric antigen receptor T cell efficacy","volume":"127","author":"Beavis","year":"2017","journal-title":"J. Clin. Invest."},{"key":"ref_172","doi-asserted-by":"crossref","first-page":"115","DOI":"10.1158\/0008-5472.CAN-16-2684","article-title":"CD39 expression defines cell exhaustion in tumor-Infiltrating CD8(+) T cells","volume":"78","author":"Canale","year":"2018","journal-title":"Cancer Res."},{"key":"ref_173","first-page":"129","article-title":"Anti-CD39 and anti-CD73 antibodies A1 and 7G2 improve targeted therapy in ovarian cancer by blocking adenosine-dependent immune evasion","volume":"6","author":"Diessner","year":"2014","journal-title":"Am. J. Transl. Res."},{"key":"ref_174","doi-asserted-by":"crossref","first-page":"202","DOI":"10.1182\/blood-2002-06-1668","article-title":"CTLA-4 is not restricted to the lymphoid cell lineage and can function as a target molecule for apoptosis induction of leukemic cells","volume":"101","author":"Pistillo","year":"2003","journal-title":"Blood"},{"key":"ref_175","doi-asserted-by":"crossref","first-page":"538","DOI":"10.1002\/ijc.21155","article-title":"CTLA-4 is constitutively expressed on tumor cells and can trigger apoptosis upon ligand interaction","volume":"117","author":"Contardi","year":"2005","journal-title":"Int. J. Cancer"},{"key":"ref_176","doi-asserted-by":"crossref","first-page":"2330","DOI":"10.1056\/NEJMoa1808777","article-title":"Immune escape of relapsed AML cells after allogeneic transplantation","volume":"379","author":"Christopher","year":"2018","journal-title":"N. Engl. J. Med."},{"key":"ref_177","doi-asserted-by":"crossref","first-page":"59","DOI":"10.1186\/s13045-019-0746-1","article-title":"Immune checkpoint blockade and CAR-T cell therapy in hematologic malignancies","volume":"12","author":"Wang","year":"2019","journal-title":"J. Hematol. Oncol."},{"key":"ref_178","doi-asserted-by":"crossref","first-page":"4501","DOI":"10.1182\/blood-2010-10-310425","article-title":"Coexpression of Tim-3 and PD-1 identifies a CD8+ T-cell exhaustion phenotype in mice with disseminated acute myelogenous leukemia","volume":"117","author":"Zhou","year":"2011","journal-title":"Blood"},{"key":"ref_179","doi-asserted-by":"crossref","first-page":"3130","DOI":"10.1172\/JCI83092","article-title":"Human CAR T cells with cell-intrinsic PD-1 checkpoint blockade resist tumor-mediated inhibition","volume":"126","author":"Cherkassky","year":"2016","journal-title":"J. Clin. Invest."},{"key":"ref_180","doi-asserted-by":"crossref","first-page":"3025","DOI":"10.1200\/JCO.2017.35.15_suppl.3025","article-title":"Characterization of anti-CD19 chimeric antigen receptor (CAR) T cell-mediated tumor microenvironment immune gene profile in a multicenter trial (ZUMA-1) with axicabtagene ciloleucel (axi-cel, KTE-C19)","volume":"35","author":"Galon","year":"2017","journal-title":"J. Clin. Oncol."},{"key":"ref_181","first-page":"460","article-title":"The advantages of PD1 activating chimeric receptor (PD1-ACR) engineered lymphocytes for PDL1(+) cancer therapy","volume":"7","author":"Tang","year":"2015","journal-title":"Am. J. Transl. Res."},{"key":"ref_182","doi-asserted-by":"crossref","unstructured":"Li, T., and Wang, J. (2020). Therapeutic effect of dual CAR-T targeting PDL1 and MUC16 antigens on ovarian cancer cells in mice. BMC Cancer, 20.","DOI":"10.1186\/s12885-020-07180-x"},{"key":"ref_183","doi-asserted-by":"crossref","unstructured":"Stadtmauer, E.A., Fraietta, J.A., Davis, M.M., Cohen, A.D., Weber, K.L., Lancaster, E., Mangan, P.A., Kulikovskaya, I., Gupta, M., and Chen, F. (2020). CRISPR-engineered T cells in patients with refractory cancer. Science, 367.","DOI":"10.1126\/science.aba7365"},{"key":"ref_184","doi-asserted-by":"crossref","first-page":"486","DOI":"10.1038\/nri3862","article-title":"Molecular and cellular insights into T cell exhaustion","volume":"15","author":"Wherry","year":"2015","journal-title":"Nat. Rev. Immunol."},{"key":"ref_185","doi-asserted-by":"crossref","first-page":"97","DOI":"10.1111\/imr.12520","article-title":"Tim-3 and its role in regulating anti-tumor immunity","volume":"276","author":"Das","year":"2017","journal-title":"Immunol. Rev."},{"key":"ref_186","doi-asserted-by":"crossref","first-page":"143","DOI":"10.1056\/NEJMoa1601202","article-title":"Ipilimumab for patients with relapse after allogeneic transplantation","volume":"375","author":"Davids","year":"2016","journal-title":"N. Engl. J. Med."},{"key":"ref_187","doi-asserted-by":"crossref","first-page":"370","DOI":"10.1158\/2159-8290.CD-18-0774","article-title":"Efficacy, safety, and biomarkers of response to azacitidine and nivolumab in relapsed\/refractory acute myeloid leukemia: A nonrandomized, open-label, phase II study","volume":"9","author":"Daver","year":"2019","journal-title":"Cancer Discov."},{"key":"ref_188","doi-asserted-by":"crossref","first-page":"829","DOI":"10.1182\/blood-2019-122896","article-title":"Efficacy and safety of azacitidine (aza) in combination with the anti-PD-L1 durvalumab (durva) for the front-line treatment of older patients (pts) wiht acute myeloid leukemia (AML) who are unfit for intensive chemotherapy (IC) and pts with higher-risk myelodysplastic syndromes (HR-MDS): Results from a large, international, randomized phase 2 study [abstract]","volume":"134","author":"Zeidan","year":"2019","journal-title":"Blood"},{"key":"ref_189","doi-asserted-by":"crossref","first-page":"1507","DOI":"10.1056\/NEJMoa1407222","article-title":"Chimeric antigen receptor T cells for sustained remissions in leukemia","volume":"371","author":"Maude","year":"2014","journal-title":"N. Engl. J. Med."},{"key":"ref_190","doi-asserted-by":"crossref","unstructured":"O\u2019Rourke, D.M., Nasrallah, M.P., Desai, A., Melenhorst, J.J., Mansfield, K., Morrissette, J.J.D., Martinez-Lage, M., Brem, S., Maloney, E., and Shen, A. (2017). A single dose of peripherally infused EGFRvIII-directed CAR T cells mediates antigen loss and induces adaptive resistance in patients with recurrent glioblastoma. Sci. Transl. Med., 9.","DOI":"10.1126\/scitranslmed.aaa0984"},{"key":"ref_191","doi-asserted-by":"crossref","first-page":"517","DOI":"10.1016\/S0140-6736(14)61403-3","article-title":"T cells expressing CD19 chimeric antigen receptors for acute lymphoblastic leukaemia in children and young adults: A phase 1 dose-escalation trial","volume":"385","author":"Lee","year":"2015","journal-title":"Lancet"},{"key":"ref_192","doi-asserted-by":"crossref","first-page":"2406","DOI":"10.1182\/blood-2015-08-665547","article-title":"Acquisition of a CD19-negative myeloid phenotype allows immune escape of MLL-rearranged B-ALL from CD19 CAR-T-cell therapy","volume":"127","author":"Gardner","year":"2016","journal-title":"Blood"},{"key":"ref_193","doi-asserted-by":"crossref","first-page":"2123","DOI":"10.1172\/JCI85309","article-title":"CD19 CAR-T cells of defined CD4+:CD8+ composition in adult B cell ALL patients","volume":"126","author":"Turtle","year":"2016","journal-title":"J. Clin. Invest."},{"key":"ref_194","doi-asserted-by":"crossref","first-page":"218","DOI":"10.1182\/blood.V128.22.218.218","article-title":"Long-term outcomes following CD19 CAR T cell therapy for B-ALL are superior in patients receiving a fludarabine\/cyclophosphamide preparative regimen and post-CAR hematopoietic stem cell transplantation","volume":"128","author":"Yuan","year":"2016","journal-title":"Blood"},{"key":"ref_195","doi-asserted-by":"crossref","first-page":"1219","DOI":"10.1158\/2159-8290.CD-18-0442","article-title":"Tumor antigen escape from CAR T-cell therapy","volume":"8","author":"Majzner","year":"2018","journal-title":"Cancer Discov"},{"key":"ref_196","doi-asserted-by":"crossref","first-page":"e186","DOI":"10.1097\/HS9.0000000000000186","article-title":"CAR T cell toxicity: Current management and future directions","volume":"3","author":"Perales","year":"2019","journal-title":"Hemasphere"},{"key":"ref_197","doi-asserted-by":"crossref","first-page":"43","DOI":"10.2147\/ITT.S202015","article-title":"Cytokine release syndrome: Current perspectives","volume":"8","author":"Murthy","year":"2019","journal-title":"Immunotargets Ther."},{"key":"ref_198","doi-asserted-by":"crossref","first-page":"195","DOI":"10.1080\/17474086.2019.1585238","article-title":"Management of cytokine release syndrome and neurotoxicity in chimeric antigen receptor (CAR) T cell therapy","volume":"12","author":"Acharya","year":"2019","journal-title":"Expert Rev. Hematol."},{"key":"ref_199","doi-asserted-by":"crossref","first-page":"4235","DOI":"10.2217\/fon-2019-0467","article-title":"Clinical care of chimeric antigen receptor T-cell patients and managing immune-related adverse effects in the ambulatory and hospitalized setting: A review","volume":"15","author":"Hays","year":"2019","journal-title":"Future Oncol."},{"key":"ref_200","doi-asserted-by":"crossref","first-page":"130","DOI":"10.1007\/s11899-020-00567-4","article-title":"The cardiovascular complications of chimeric antigen receptor T cell therapy","volume":"15","author":"Jamal","year":"2020","journal-title":"Curr. Hematol. Malig. Rep."},{"key":"ref_201","doi-asserted-by":"crossref","unstructured":"Greenbaum, U., Kebriaei, P., Srour, S.A., Olson, A., Bashir, Q., Neelapu, S.S., Rezvani, K., and Shpall, E.J. (2020). Chimeric antigen receptor T-cell therapy toxicities. Br. J. Clin. Pharmacol.","DOI":"10.1111\/bcp.14403"},{"key":"ref_202","doi-asserted-by":"crossref","unstructured":"Siegler, E.L., and Kenderian, S.S. (2020). Neurotoxicity and cytokine release syndrome after chimeric antigen receptor T cell therapy: Insights Into mechanisms and novel therapies. Front. Immunol., 11.","DOI":"10.3389\/fimmu.2020.01973"},{"key":"ref_203","doi-asserted-by":"crossref","first-page":"953","DOI":"10.1016\/j.ncl.2020.08.001","article-title":"A concise review of neurologic complications associated with chimeric antigen receptor T-cell immunotherapy","volume":"38","author":"Ruff","year":"2020","journal-title":"Neurol. Clin."},{"key":"ref_204","doi-asserted-by":"crossref","first-page":"2295","DOI":"10.1182\/blood-2017-06-793141","article-title":"Kinetics and biomarkers of severe cytokine release syndrome after CD19 chimeric antigen receptor-modified T-cell therapy","volume":"130","author":"Hay","year":"2017","journal-title":"Blood"},{"key":"ref_205","doi-asserted-by":"crossref","first-page":"355ra116","DOI":"10.1126\/scitranslmed.aaf8621","article-title":"Immunotherapy of non-Hodgkin\u2019s lymphoma with a defined ratio of CD8+ and CD4+ CD19-specific chimeric antigen receptor-modified T cells","volume":"8","author":"Turtle","year":"2016","journal-title":"Sci. Transl. Med."},{"key":"ref_206","doi-asserted-by":"crossref","first-page":"45","DOI":"10.1056\/NEJMoa1804980","article-title":"Tisagenlecleucel in adult relapsed or refractory diffuse large B-cell lymphoma","volume":"380","author":"Schuster","year":"2019","journal-title":"N. Engl. J. Med."},{"key":"ref_207","doi-asserted-by":"crossref","first-page":"839","DOI":"10.1016\/S0140-6736(20)31366-0","article-title":"Lisocabtagene maraleucel for patients with relapsed or refractory large B-cell lymphomas (TRANSCEND NHL 001): A multicentre seamless design study","volume":"396","author":"Abramson","year":"2020","journal-title":"Lancet"},{"key":"ref_208","doi-asserted-by":"crossref","first-page":"1311","DOI":"10.2741\/4181","article-title":"Antibody-based therapy of acute myeloid leukemia with gemtuzumab ozogamicin","volume":"18","author":"Cowan","year":"2013","journal-title":"Front. Biosci."},{"key":"ref_209","doi-asserted-by":"crossref","first-page":"2330","DOI":"10.1182\/blood-2017-01-762419","article-title":"Sinusoidal obstruction syndrome following CD33-targeted therapy in acute myeloid leukemia","volume":"129","author":"Godwin","year":"2017","journal-title":"Blood"},{"key":"ref_210","doi-asserted-by":"crossref","first-page":"724","DOI":"10.3324\/haematol.2016.141937","article-title":"Defining the dose of gemtuzumab ozogamicin in combination with induction chemotherapy in acute myeloid leukemia: A comparison of 3 mg\/m2 with 6 mg\/m2 in the NCRI AML17 Trial","volume":"101","author":"Burnett","year":"2016","journal-title":"Haematologica"},{"key":"ref_211","doi-asserted-by":"crossref","first-page":"623","DOI":"10.1200\/JCO.19.01406","article-title":"Gemtuzumab ozogamicin in NPM1-mutated acute myeloid leukemia: Early results from the prospective randomized AMLSG 09-09 phase III study","volume":"38","author":"Schlenk","year":"2020","journal-title":"J. Clin. Oncol."},{"key":"ref_212","doi-asserted-by":"crossref","first-page":"1455","DOI":"10.1182\/blood-2013-03-491506","article-title":"SGN-CD33A: A novel CD33-targeting antibody-drug conjugate using a pyrrolobenzodiazepine dimer is active in models of drug-resistant AML","volume":"122","author":"Walter","year":"2013","journal-title":"Blood"},{"key":"ref_213","doi-asserted-by":"crossref","first-page":"380","DOI":"10.1016\/j.immuni.2016.01.021","article-title":"Distinct signaling of coreceptors regulates specific metabolism pathways and impacts memory development in CAR T cells","volume":"44","author":"Kawalekar","year":"2016","journal-title":"Immunity"},{"key":"ref_214","doi-asserted-by":"crossref","first-page":"1160","DOI":"10.1038\/leu.2010.75","article-title":"Engineering CD19-specific T lymphocytes with interleukin-15 and a suicide gene to enhance their anti-lymphoma\/leukemia effects and safety","volume":"24","author":"Hoyos","year":"2010","journal-title":"Leukemia"},{"key":"ref_215","doi-asserted-by":"crossref","first-page":"573","DOI":"10.1007\/s13238-017-0411-9","article-title":"Increasing the safety and efficacy of chimeric antigen receptor T cell therapy","volume":"8","author":"Li","year":"2017","journal-title":"Protein Cell"},{"key":"ref_216","doi-asserted-by":"crossref","unstructured":"Ali, R., Ramdial, J., Algaze, S., and Beitinjaneh, A. (2017). The role of anti-thymocyte globulin or alemtuzumab-based serotherapy in the prophylaxis and management of graft-versus-host disease. Biomedicines, 5.","DOI":"10.3390\/biomedicines5040067"},{"key":"ref_217","doi-asserted-by":"crossref","first-page":"1439","DOI":"10.1016\/j.cell.2018.05.013","article-title":"Genetic inactivation of CD33 in hematopoietic stem cells to enable CAR T cell immunotherapy for acute myeloid leukemia","volume":"173","author":"Kim","year":"2018","journal-title":"Cell"},{"key":"ref_218","doi-asserted-by":"crossref","first-page":"762","DOI":"10.1038\/s41375-018-0277-8","article-title":"Engineering resistance to CD33-targeted immunotherapy in normal hematopoiesis by CRISPR\/Cas9-deletion of CD33 exon 2","volume":"33","author":"Humbert","year":"2019","journal-title":"Leukemia"},{"key":"ref_219","doi-asserted-by":"crossref","first-page":"11978","DOI":"10.1073\/pnas.1819992116","article-title":"Gene-edited stem cells enable CD33-directed immune therapy for myeloid malignancies","volume":"116","author":"Borot","year":"2019","journal-title":"Proc. Natl. Acad. Sci. 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