{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,21]],"date-time":"2026-09-21T02:47:49Z","timestamp":1789958869501,"version":"4.0.1"},"reference-count":143,"publisher":"MDPI AG","issue":"1","license":[{"start":{"date-parts":[[2025,12,29]],"date-time":"2025-12-29T00:00:00Z","timestamp":1766966400000},"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>Acute myeloid leukemia (AML) is an aggressive cancer with rapid progression and a high relapse rate, highlighting the urgent need for effective treatments. While recent advances in drug therapies and combination regimens have improved outcomes, relapsed and refractory (R\/R) AML still shows low response rates, poor prognosis, and limited survival. The lack of effective immunotherapies further complicates the management of R\/R AML. The bone marrow tumor microenvironment (TME) poses a significant barrier, requiring multifaceted, combined therapeutic strategies for clinical success. This TME creates an immunosuppressive and metabolically challenging environment that limits the expansion, persistence, cytotoxicity, and survival of chimeric antigen receptor (CAR) T cells. Unlike CD19 in B-cell acute lymphoblastic leukemia (B-ALL), AML lacks a truly leukemia-specific antigen. Although clinical trials are ongoing, no CAR-T therapies have received FDA approval for AML. This paper explores the reasons behind these ongoing challenges.<\/jats:p>","DOI":"10.3390\/cancers18010107","type":"journal-article","created":{"date-parts":[[2025,12,31]],"date-time":"2025-12-31T13:30:52Z","timestamp":1767187852000},"page":"107","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":5,"title":["Is There a Future for CAR-T Therapy in Acute Myeloid Leukemia?"],"prefix":"10.3390","volume":"18","author":[{"given":"Caterina","family":"Alati","sequence":"first","affiliation":[{"name":"Hematology and Stem Cell Transplantation and Cellular Therapies Unit (CTMO), Department of Hemato-Oncology and Radiotherapy, Grande Ospedale Metropolitano \u201cBianchi-Melacrino-Morelli\u201d, 89133 Reggio Calabria, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3982-4141","authenticated-orcid":false,"given":"Martina","family":"Pitea","sequence":"additional","affiliation":[{"name":"Hematology and Stem Cell Transplantation and Cellular Therapies Unit (CTMO), Department of Hemato-Oncology and Radiotherapy, Grande Ospedale Metropolitano \u201cBianchi-Melacrino-Morelli\u201d, 89133 Reggio Calabria, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6391-4406","authenticated-orcid":false,"given":"Matteo","family":"Molica","sequence":"additional","affiliation":[{"name":"Department of Hematology-Oncology, Azienda Universitaria Ospedaliera Renato Dulbecco, 88100 Catanzaro, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7258-475X","authenticated-orcid":false,"given":"Marco","family":"Rossi","sequence":"additional","affiliation":[{"name":"Department of Hematology-Oncology, Azienda Universitaria Ospedaliera Renato Dulbecco, 88100 Catanzaro, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maria Eugenia","family":"Alvaro","sequence":"additional","affiliation":[{"name":"Division of Hematology, Department of Human Pathology in Adulthood and Childhood \u201cGaetano Barresi\u201d, University of Messina, via Consolare Valeria, 98125 Messina, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4739-349X","authenticated-orcid":false,"given":"Gaetana","family":"Porto","sequence":"additional","affiliation":[{"name":"Hematology and Stem Cell Transplantation and Cellular Therapies Unit (CTMO), Department of Hemato-Oncology and Radiotherapy, Grande Ospedale Metropolitano \u201cBianchi-Melacrino-Morelli\u201d, 89133 Reggio Calabria, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0005-2684-9269","authenticated-orcid":false,"given":"Erica","family":"Bilardi","sequence":"additional","affiliation":[{"name":"Hematology and Stem Cell Transplantation and Cellular Therapies Unit (CTMO), Department of Hemato-Oncology and Radiotherapy, Grande Ospedale Metropolitano \u201cBianchi-Melacrino-Morelli\u201d, 89133 Reggio Calabria, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Giovanna","family":"Utano","sequence":"additional","affiliation":[{"name":"Hematology and Stem Cell Transplantation and Cellular Therapies Unit (CTMO), Department of Hemato-Oncology and Radiotherapy, Grande Ospedale Metropolitano \u201cBianchi-Melacrino-Morelli\u201d, 89133 Reggio Calabria, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0008-5857-7247","authenticated-orcid":false,"given":"Giorgia","family":"Policastro","sequence":"additional","affiliation":[{"name":"Hematology and Stem Cell Transplantation and Cellular Therapies Unit (CTMO), Department of Hemato-Oncology and Radiotherapy, Grande Ospedale Metropolitano \u201cBianchi-Melacrino-Morelli\u201d, 89133 Reggio Calabria, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0006-6931-4632","authenticated-orcid":false,"given":"Maria Caterina","family":"Mic\u00f2","sequence":"additional","affiliation":[{"name":"Hematology and Stem Cell Transplantation and Cellular Therapies Unit (CTMO), Department of Hemato-Oncology and Radiotherapy, Grande Ospedale Metropolitano \u201cBianchi-Melacrino-Morelli\u201d, 89133 Reggio Calabria, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Violetta","family":"Marafioti","sequence":"additional","affiliation":[{"name":"Hematology and Stem Cell Transplantation and Cellular Therapies Unit (CTMO), Department of Hemato-Oncology and Radiotherapy, Grande Ospedale Metropolitano \u201cBianchi-Melacrino-Morelli\u201d, 89133 Reggio Calabria, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3987-419X","authenticated-orcid":false,"given":"Massimo","family":"Martino","sequence":"additional","affiliation":[{"name":"Hematology and Stem Cell Transplantation and Cellular Therapies Unit (CTMO), Department of Hemato-Oncology and Radiotherapy, Grande Ospedale Metropolitano \u201cBianchi-Melacrino-Morelli\u201d, 89133 Reggio Calabria, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2025,12,29]]},"reference":[{"key":"ref_1","first-page":"10","article-title":"Cancer statistics, 2025","volume":"75","author":"Siegel","year":"2025","journal-title":"CA Cancer J. Clin."},{"key":"ref_2","unstructured":"(2023, March 07). SEER 22, 2015\u20132019; Cancer Stat Facts: Leukemia\u2014Acute Myeloid Leukemia (AML), Available online: https:\/\/seer.cancer.gov\/statfacts\/html\/amyl.html."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"1345","DOI":"10.1182\/blood.2022016867","article-title":"Diagnosis and management of AML in adults: 2022 recommendations from an international expert panel on behalf of the ELN","volume":"140","author":"Wei","year":"2022","journal-title":"Blood"},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"S54","DOI":"10.1016\/j.clml.2011.02.003","article-title":"Older patients with acute myeloid leukemia benefit from intensive chemotherapy: An update from the Swedish Acute Leukemia Registry","volume":"11","author":"Juliusson","year":"2011","journal-title":"Clin. Lymphoma Myeloma Leuk."},{"key":"ref_5","unstructured":"European Medicines Agency (2025, March 01). Advanced Therapy Medicinal Products: Overview. Available online: https:\/\/www.ema.europa.eu\/en\/human-regulatory-overview\/advanced-therapy-medicinal-products-overview."},{"key":"ref_6","unstructured":"US Food and Drug Administration (2025, March 01). Considerations for the Development of Chimeric Antigen Receptor (CAR) T Cell Products: Guidance for Industry, Available online: https:\/\/www.fda.gov\/regulatory-information\/search-fda-guidance-documents\/considerations-development-chimeric-antigen-receptor-car-t-cell-products."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"1069","DOI":"10.1038\/s41409-023-02072-7","article-title":"Implementation and operational management of marketed chimeric antigen receptor T cell (CAR-T Cell) therapy-a guidance by the GoCART Coalition Pharmacist Working Group","volume":"58","author":"Langebrake","year":"2023","journal-title":"Bone Marrow Transpl."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"261","DOI":"10.1016\/j.jcyt.2020.11.008","article-title":"Comparison of regulatory pathways for the approval of advanced therapies in the European Union and the United States","volume":"23","author":"Obach","year":"2021","journal-title":"Cytotherapy"},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"4417","DOI":"10.1200\/JCO.2011.35.7525","article-title":"Prediction of early death after induction therapy for newly diagnosed acute myeloid leukemia with pretreatment risk scores: A novel paradigm for treatment assignment","volume":"29","author":"Walter","year":"2011","journal-title":"J. Clin. Oncol."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"2000","DOI":"10.1016\/S0140-6736(10)62105-8","article-title":"Complete remission and early death after intensive chemotherapy in patients aged 60 years or older with acute myeloid leukaemia: A web-based application for prediction of outcomes","volume":"376","author":"Krug","year":"2010","journal-title":"Lancet"},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"997","DOI":"10.1038\/leu.2012.303","article-title":"Consensus-based definition of unfitness to intensive and non-intensive chemotherapy in acute myeloidleukemia: A project of SIE, SIES and GITMO group on a new tool for therapy decision making","volume":"27","author":"Ferrara","year":"2013","journal-title":"Leukemia"},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"1571","DOI":"10.1016\/S0140-6736(23)00464-6","article-title":"Quizartinib plus chemotherapy in newly diagnosed patients with FLT3-internal-tandem-duplication-positive acute myeloid leukaemia (QuANTUM-First): A randomised, double-blind, placebo-controlled, phase 3 trial","volume":"401","author":"Erba","year":"2023","journal-title":"Lancet"},{"key":"ref_13","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_14","doi-asserted-by":"crossref","unstructured":"Liu, Y., Zhang, Y., Gao, J., Wang, L., Xie, F., Zhang, C., Mao, P., and Yan, J. (2025). Venetoclax and hypomethylating agents versus induction chemotherapy for newly diagnosed acute myeloid leukemia patients: A systematic review and meta-analysis. BMC Cancer, 25.","DOI":"10.1186\/s12885-025-14311-9"},{"key":"ref_15","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_16","doi-asserted-by":"crossref","first-page":"291","DOI":"10.1182\/blood-2015-01-621664","article-title":"International phase 3 study of azacitidine vs conventional care regimens in older patients with newly diagnosed AML with >30% blasts","volume":"126","author":"Dombret","year":"2015","journal-title":"Blood"},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"323","DOI":"10.1080\/17474086.2025.2487605","article-title":"Oral decitabine in acute myeloid leukemia: Assessing efficacy, safety, and future implications for older patients","volume":"18","author":"Niscola","year":"2025","journal-title":"Expert Rev. Hematol."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"2684","DOI":"10.1200\/JCO.2017.77.6112","article-title":"CPX-351 (cytarabine and daunorubicin) Liposome for Injection Versus Conventional Cytarabine Plus Daunorubicin in Older Patients with Newly Diagnosed Secondary Acute Myeloid Leukemia","volume":"36","author":"Lancet","year":"2018","journal-title":"J. Clin. Oncol."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"234","DOI":"10.1002\/cncr.28974","article-title":"Phase II, multicenter, randomized trial of CPX-351 (cytarabine:daunorubicin) liposome injection versus intensive salvage therapy in adults with first relapse AML","volume":"121","author":"Cortes","year":"2015","journal-title":"Cancer"},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"972","DOI":"10.1200\/JCO.2015.64.0060","article-title":"Gemtuzumab Ozogamicin Versus Best Supportive Care in Older Patients withNewly Diagnosed Acute Myeloid Leukemia Unsuitable for Intensive Chemotherapy: Results of the Randomized Phase III EORTC-GIMEMA AML-19 Trial","volume":"34","author":"Amadori","year":"2016","journal-title":"J. Clin. Oncol."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"257","DOI":"10.1182\/blood-2016-10-745133","article-title":"Preclinical studies of gilteritinib, a next-generation FLT3 inhibitor","volume":"129","author":"Lee","year":"2017","journal-title":"Blood"},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"454","DOI":"10.1056\/NEJMoa1614359","article-title":"Midostaurin plus Chemotherapy for Acute Myeloid Leukemia with a FLT3 Mutation","volume":"377","author":"Stone","year":"2017","journal-title":"N. Engl. J. Med."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"1571","DOI":"10.2217\/fon.14.105","article-title":"Quizartinib for the treatment of FLT3\/ITD acute myeloid leukemia","volume":"10","author":"Levis","year":"2014","journal-title":"Future Oncol."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"1121","DOI":"10.1111\/bjh.19944","article-title":"Olutasidenib demonstrates significant clinical activity in mutated IDH1 acute myeloid leukaemia arising from a prior myeloproliferative neoplasm","volume":"206","author":"Cortes","year":"2025","journal-title":"Br. J. Haematol."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"429","DOI":"10.1182\/bloodadvances.2023010563","article-title":"A study to assess the efficacy of enasidenib and risk-adapted addition of azacitidine in newly diagnosed IDH2-mutant AML","volume":"8","author":"Cai","year":"2024","journal-title":"Blood Adv."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"108","DOI":"10.1097\/MOH.0000000000000561","article-title":"Relapsed or primary refractory AML: Moving past MEC and FLAG-ida","volume":"27","author":"Koenig","year":"2020","journal-title":"Curr. Opin. Hematol."},{"key":"ref_27","doi-asserted-by":"crossref","unstructured":"Tenold, M.E., Moskoff, B.N., Benjamin, D.J., Hoeg, R.T., Rosenberg, A.S., Abedi, M., Tuscano, J.M., and Jonas, B.A. (2021). Outcomes of Adults with Relapsed\/Refractory Acute Myeloid Leukemia Treated with Venetoclax Plus Hypomethylating Agents at a Comprehensive Cancer Center. Front. Oncol., 11.","DOI":"10.3389\/fonc.2021.649209"},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"e572","DOI":"10.1097\/HS9.0000000000000572","article-title":"Treatment for Relapsed\/Refractory Acute Myeloid Leukemia","volume":"5","author":"Thol","year":"2021","journal-title":"Hemasphere"},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"1728","DOI":"10.1056\/NEJMoa1902688","article-title":"Gilteritinib or Chemotherapy for Relapsed or Refractory FLT3-Mutated AML","volume":"381","author":"Perl","year":"2019","journal-title":"N. Engl. J. Med."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"984","DOI":"10.1016\/S1470-2045(19)30150-0","article-title":"Quizartinib versus salvage chemotherapy in relapsed or refractory FLT3-ITD acute myeloid leukaemia (QuANTUM-R): A multicentre, randomised, controlled, open-label, phase 3 trial","volume":"20","author":"Cortes","year":"2019","journal-title":"Lancet Oncol."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"519","DOI":"10.1038\/s41409-025-02524-2","article-title":"The 2023 EBMT report on hematopoietic cell transplantation and cellular therapies. Increased use of allogeneic HCT for myeloid malignancies and of CAR-T at the expense of autologous HCT","volume":"60","author":"Passweg","year":"2025","journal-title":"Bone Marrow Transpl."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"505","DOI":"10.1016\/j.jtct.2025.05.014","article-title":"Current Activity Trends and Outcomes in Hematopoietic Cell Transplantation and Cellular Therapy\u2014A Report from the CIBMTR","volume":"31","author":"Spellman","year":"2025","journal-title":"Transplant. Cell Ther."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"62","DOI":"10.1182\/blood-2015-07-604546","article-title":"Hematopoietic stem cell transplantation for patients with AML in first complete remission","volume":"127","author":"Cornelissen","year":"2016","journal-title":"Blood"},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"1903","DOI":"10.1182\/blood.2023023568","article-title":"Management of ALL in adults: 2024 ELN recommendations from a European expert panel","volume":"143","author":"Boissel","year":"2024","journal-title":"Blood"},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"2526","DOI":"10.1056\/NEJMoa2004444","article-title":"QUAZAR AML-001 Trial Investigators. Oral Azacitidine Maintenance Therapy for Acute Myeloid Leukemia in First Remission","volume":"383","author":"Wei","year":"2020","journal-title":"N. Engl. J. Med."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"2386","DOI":"10.1056\/NEJMoa1716984","article-title":"Durable Remissions with Ivosidenib in IDH1-Mutated Relapsed or Refractory AML","volume":"378","author":"DiNardo","year":"2018","journal-title":"N. Engl. J. Med."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"211","DOI":"10.1080\/17474086.2024.2354486","article-title":"Olutasidenib: A novel mutant IDH1 inhibitor for the treatment of relapsed or refractory acute myeloid leukemia","volume":"17","author":"Cortes","year":"2024","journal-title":"Expert Rev. Hematol."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"722","DOI":"10.1182\/blood-2017-04-779405","article-title":"Enasidenib in mutant IDH2 relapsed or refractory acute myeloid leukemia","volume":"130","author":"Stein","year":"2017","journal-title":"Blood"},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"113","DOI":"10.1186\/s13045-024-01632-8","article-title":"Menin inhibitors for the treatment of acute myeloid leukemia: Challenges and opportunities ahead","volume":"17","author":"Nadiminti","year":"2024","journal-title":"J. Hematol. Oncol."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"1023","DOI":"10.1182\/blood.2019001982","article-title":"How I treat relapsed or refractory AML","volume":"136","author":"DeWolf","year":"2020","journal-title":"Blood"},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"614","DOI":"10.1038\/s41375-024-02501-6","article-title":"A novel prognostic risk model for patients with refractory\/relapsed acute myeloid leukemia receiving venetoclax plus hypomethylating agents","volume":"39","author":"Shahswar","year":"2025","journal-title":"Leukemia"},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"13","DOI":"10.1038\/s41375-021-01350-x","article-title":"Catch me if you can: How AML and its niche escape immunotherapy","volume":"36","author":"Tettamanti","year":"2022","journal-title":"Leukemia"},{"key":"ref_43","doi-asserted-by":"crossref","unstructured":"Isidori, A., Cerchione, C., Daver, N., DiNardo, C., Garcia-Manero, G., Konopleva, M., Jabbour, E., Ravandi, F., Kadia, T., and Burguera, A.d.l.F. (2021). Immunotherapy in Acute Myeloid Leukemia: Where We Stand. Front. Oncol., 11.","DOI":"10.3389\/fonc.2021.656218"},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"234","DOI":"10.1158\/2643-3230.BCD-23-0202","article-title":"Recent Advances in Immune-Based Therapies for Acute Myeloid Leukemia","volume":"5","author":"Restelli","year":"2024","journal-title":"Blood Cancer Discov."},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"57","DOI":"10.1186\/s40164-025-00651-6","article-title":"Breakthroughs of CAR T-cell therapy in acute myeloid leukemia: Updates from ASH 2024","volume":"14","author":"Zhang","year":"2025","journal-title":"Exp. Hematol. Oncol."},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1177\/20406207241263489","article-title":"Recent advances in CAR-T therapy for the treatment of acute myeloid leukemia","volume":"15","author":"Zha","year":"2024","journal-title":"Ther. Adv. Hematol."},{"key":"ref_47","doi-asserted-by":"crossref","unstructured":"Wei, W., Yang, D., Chen, X., Liang, D., Zou, L., and Zhao, X. (2022). Chimeric antigen receptor T-cell therapy for T-ALL and AML. Front. Oncol., 12.","DOI":"10.3389\/fonc.2022.967754"},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"211","DOI":"10.1080\/13543784.2022.2032642","article-title":"Prospect of CAR T-cell therapy in acute myeloid leukemia","volume":"31","author":"Badar","year":"2022","journal-title":"Expert Opin. Investig. Drugs"},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"e937","DOI":"10.1097\/HS9.0000000000000937","article-title":"CAR-T in the Treatment of Acute Myeloid Leukemia: Barriers and How to Overcome Them","volume":"7","author":"Vanhooren","year":"2023","journal-title":"Hemasphere"},{"key":"ref_50","doi-asserted-by":"crossref","unstructured":"Michelozzi, I.M., Kirtsios, E., and Giustacchini, A. (2021). Driving CAR T Stem Cell Targeting in Acute Myeloid Leukemia: The Roads to Success. Cancers, 13.","DOI":"10.3390\/cancers13112816"},{"key":"ref_51","doi-asserted-by":"crossref","unstructured":"Epperly, R., Gottschalk, S., and Velasquez, M.P. (2020). A Bump in the Road: How the Hostile AML Microenvironment Affects CAR T Cell Therapy. Front. Oncol., 10.","DOI":"10.3389\/fonc.2020.00262"},{"key":"ref_52","doi-asserted-by":"crossref","unstructured":"Damiani, D., and Tiribelli, M. (2024). CAR-T Cells in Acute Myeloid Leukemia: Where Do We Stand?. Biomedicines, 12.","DOI":"10.3390\/biomedicines12061194"},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"155","DOI":"10.1053\/j.seminhematol.2018.08.008","article-title":"Will CAR T cell therapy have a role in AML? Promises and pitfalls","volume":"56","author":"Cummins","year":"2019","journal-title":"Semin. Hematol."},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"135","DOI":"10.1186\/s40164-025-00726-4","article-title":"Emerging strategies in CAR-T cell therapy for acute myeloid leukemia: Overcoming heterogeneity and improving safety through dual-antigen targeting","volume":"14","author":"Mutis","year":"2025","journal-title":"Exp. Hematol. Oncol."},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"e70536","DOI":"10.1002\/ctm2.70536","article-title":"CAR-DC combined with CAR-T therapy for relapsed\/refractory acute myeloid leukaemia: Research progress and future perspectives","volume":"15","author":"Zhang","year":"2025","journal-title":"Clin. Transl. Med."},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"210","DOI":"10.1038\/s41392-025-02269-w","article-title":"CAR-T cell therapy for cancer: Current challenges and future directions","volume":"10","author":"Zugasti","year":"2025","journal-title":"Sig. Transduct. Target. Ther."},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"3467","DOI":"10.1182\/blood-2024-207659","article-title":"The Safety and Efficacy of CD33 CAR-T Therapy for RR AML after HSCT","volume":"144","author":"Lin","year":"2024","journal-title":"Blood"},{"key":"ref_58","doi-asserted-by":"crossref","first-page":"2076","DOI":"10.1182\/blood-2024-208795","article-title":"CD123-CAR T Cells Manufactured in the Presence of Dasatinib Induce High Grade CRS and\/or IEC-HS without Improving Efficacy in Pediatric Patients with Recurrent\/Refractory Leukemia","volume":"144","author":"Naik","year":"2024","journal-title":"Blood"},{"key":"ref_59","doi-asserted-by":"crossref","first-page":"888","DOI":"10.1186\/s12967-024-05705-7","article-title":"Efficacy and safety of CAR-T therapy targeting CLL1 in patients with extramedullary diseases of acute myeloid leukemia","volume":"22","author":"Zhao","year":"2024","journal-title":"J. Transl. Med."},{"key":"ref_60","doi-asserted-by":"crossref","first-page":"7210","DOI":"10.1182\/blood-2024-204381","article-title":"Development of This CART371 targeting CLL1 for the treatment of relapsed\/refractory acute myeloid leukemia","volume":"144","author":"Zhang","year":"2024","journal-title":"Blood"},{"key":"ref_61","doi-asserted-by":"crossref","first-page":"6018","DOI":"10.1182\/blood-2024-202265","article-title":"Distribution of infectious complications following CLL1 CAR-T cell therapy for R\/R AML: A Single-Center experience","volume":"144","author":"Xu","year":"2024","journal-title":"Blood"},{"key":"ref_62","doi-asserted-by":"crossref","first-page":"2070.39541103","DOI":"10.1182\/blood-2024-194162","article-title":"CD371-Targeted CAR T-Cells secreting Interleukin-18 exhibit robust expansion and disease clearance in patients with refractory acute myeloid leukemia","volume":"144","author":"Geyer","year":"2024","journal-title":"Blood"},{"key":"ref_63","doi-asserted-by":"crossref","first-page":"4836","DOI":"10.1182\/blood-2024-207197","article-title":"Unleashing the power of CD19 CAR-T in relapsed AML: Findings from a prospective Single-Center clinical trial","volume":"144","author":"Yin","year":"2024","journal-title":"Blood"},{"key":"ref_64","doi-asserted-by":"crossref","first-page":"2441","DOI":"10.1016\/j.ymthe.2025.03.052","article-title":"CAR-T cell therapy for treatment of acute myeloid leukemia, advances and outcomes","volume":"33","author":"Khalifeh","year":"2025","journal-title":"Mol. Ther."},{"key":"ref_65","doi-asserted-by":"crossref","first-page":"64","DOI":"10.1097\/MOH.0000000000000626","article-title":"Genetic heterogeneity and clonal evolution in acute myeloid leukemia","volume":"28","author":"Meyer","year":"2021","journal-title":"Curr. Opin. Hematol."},{"key":"ref_66","doi-asserted-by":"crossref","unstructured":"Zanetti, L.C., Tomaz, V., de Souza, I.F., Campregher, P.V., Hamerschlak, N., and Kerbauy, L.N. (2025). Precision medicine with car cells in acute myeloid leukemia: Where are we?. Front. Immunol., 16.","DOI":"10.3389\/fimmu.2025.1653350"},{"key":"ref_67","doi-asserted-by":"crossref","first-page":"114260","DOI":"10.1016\/j.celrep.2024.114260","article-title":"Immunotherapeutic targeting of surfaceome heterogeneity in AML","volume":"43","author":"Bordeleau","year":"2024","journal-title":"Cell Rep."},{"key":"ref_68","doi-asserted-by":"crossref","first-page":"14331","DOI":"10.1073\/pnas.1916206117","article-title":"Reversible suppression of T cell function in the bone marrow microenvironment of acute myeloid leukemia","volume":"117","author":"Lamble","year":"2020","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_69","doi-asserted-by":"crossref","first-page":"3057","DOI":"10.1158\/1078-0432.CCR-15-2626","article-title":"T-Cell Immunoglobulin and ITIM Domain (TIGIT) Associates with CD8+ T-Cell Exhaustion and Poor Clinical Outcome in AML Patients","volume":"22","author":"Kong","year":"2016","journal-title":"Clin. Cancer Res."},{"key":"ref_70","doi-asserted-by":"crossref","unstructured":"Barakos, G.P., and Hatzimichael, E. (2022). Microenvironmental Features Driving Immune Evasion in Myelodysplastic Syndromes and Acute Myeloid Leukemia. Diseases, 10.","DOI":"10.3390\/diseases10020033"},{"key":"ref_71","doi-asserted-by":"crossref","unstructured":"Liu, M., Yang, M., Qi, Y., Ma, Y., Guo, Q., Guo, L., Liu, C., Liu, W., Xiao, L., and Yang, Y. (2025). Immunosuppressive cells in acute myeloid leukemia: Mechanisms and therapeutic target. Front. Immunol., 16.","DOI":"10.3389\/fimmu.2025.1627161"},{"key":"ref_72","doi-asserted-by":"crossref","unstructured":"Zhao, Y., Du, J., and Shen, X. (2023). Targeting myeloid-derived suppressor cells in tumor immunotherapy: Current, future and beyond. Front. Immunol., 14.","DOI":"10.3389\/fimmu.2023.1157537"},{"key":"ref_73","doi-asserted-by":"crossref","first-page":"789","DOI":"10.3390\/ijms11030789","article-title":"Interleukin 12 a key immunoregulatory cytokine in infection applications","volume":"11","author":"Hamza","year":"2010","journal-title":"Int. J. Mol. Sci."},{"key":"ref_74","doi-asserted-by":"crossref","first-page":"923","DOI":"10.1016\/j.trecan.2025.06.008","article-title":"IL-18 revives dysfunctional CAR-T cells","volume":"11","author":"Li","year":"2025","journal-title":"Trends Cancer"},{"key":"ref_75","doi-asserted-by":"crossref","first-page":"20210106","DOI":"10.1002\/EXP.20210106","article-title":"Recent advances in overcoming barriers to cell-based delivery systems for cancer immunotherapy","volume":"2","author":"Ding","year":"2022","journal-title":"Exploration"},{"key":"ref_76","doi-asserted-by":"crossref","unstructured":"Lv, Y., Luo, X., Xie, Z., Qiu, J., Yang, J., Deng, Y., Long, R., Tang, G., Zhang, C., and Zuo, J. (2024). Prospects and challenges of CAR-T cell therapy combined with ICIs. Front. Oncol., 14.","DOI":"10.3389\/fonc.2024.1368732"},{"key":"ref_77","doi-asserted-by":"crossref","first-page":"6436","DOI":"10.1038\/s41467-021-26683-0","article-title":"Demethylating therapy increases anti-CD123 CAR T cell cytotoxicity against acute myeloid leukemia","volume":"12","author":"Hughes","year":"2021","journal-title":"Nat. Commun."},{"key":"ref_78","doi-asserted-by":"crossref","first-page":"154","DOI":"10.1186\/s12943-021-01463-y","article-title":"Cancer associated-fibroblast-derived exosomes in cancer progression","volume":"20","author":"Li","year":"2021","journal-title":"Mol. Cancer"},{"key":"ref_79","doi-asserted-by":"crossref","unstructured":"Kodumudi, K.N., Siegel, J., Weber, A.M., Scott, E., Sarnaik, A.A., and Pilon-Thomas, S. (2016). Immune Checkpoint Blockade to Improve Tumor Infiltrating Lymphocytes for Adoptive Cell Therapy. PLoS ONE, 11.","DOI":"10.1371\/journal.pone.0153053"},{"key":"ref_80","doi-asserted-by":"crossref","unstructured":"Wong, K.K., Hassan, R., and Yaacob, N.S. (2021). Hypomethylating Agents and Immunotherapy: Therapeutic Synergism in Acute Myeloid Leukemia and Myelodysplastic Syndromes. Front. Oncol., 11.","DOI":"10.3389\/fonc.2021.624742"},{"key":"ref_81","doi-asserted-by":"crossref","unstructured":"Tang, L., Kong, Y., Wang, H., Zou, P., Sun, T., Liu, Y., Zhang, J., Jin, N., Mao, H., and Zhu, X. (2023). Demethylating therapy increases cytotoxicity of CD44v6 CAR-T cells against acute myeloid leukemia. Front. Immunol., 14.","DOI":"10.3389\/fimmu.2023.1145441"},{"key":"ref_82","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_83","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_84","doi-asserted-by":"crossref","first-page":"4584","DOI":"10.1182\/blood-2022-170201","article-title":"Safety and anti-leukemic activity of CD123-CAR T cells in pediatric patients with AML: Preliminary results from a phase 1 trial","volume":"140","author":"Naik","year":"2022","journal-title":"Blood"},{"key":"ref_85","doi-asserted-by":"crossref","unstructured":"Mosna, F. (2024). The immunotherapy of acute myeloid leukemia: A clinical point of view. Cancers, 16.","DOI":"10.3390\/cancers16132359"},{"key":"ref_86","doi-asserted-by":"crossref","first-page":"1428","DOI":"10.1182\/blood-2007-07-101311","article-title":"NKG2D ligand expression in AML increases in response to HDAC inhibitor valproic acid and contributes to allorecognition by NK-cell lines","volume":"111","author":"Diermayr","year":"2008","journal-title":"Blood"},{"key":"ref_87","doi-asserted-by":"crossref","first-page":"1646","DOI":"10.1182\/blood.V128.22.1646.1646","article-title":"Tumor specific glycosylated CD43 is a novel and highly specific target for acute myeloid leukemia and myelodysplastic syndrome","volume":"28","author":"Gillissen","year":"2016","journal-title":"Blood"},{"key":"ref_88","doi-asserted-by":"crossref","first-page":"11008","DOI":"10.1073\/pnas.0704271104","article-title":"CD96 is a leukemic stem cell-specific marker in human acute myeloid leukemia","volume":"104","author":"Hosen","year":"2007","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_89","doi-asserted-by":"crossref","first-page":"1777","DOI":"10.1038\/sj.leu.2401903","article-title":"The interleukin-3 receptor alpha chain is a unique marker for human acute myelogenous leukemia stem cells","volume":"14","author":"Jordan","year":"2000","journal-title":"Leukemia"},{"key":"ref_90","doi-asserted-by":"crossref","first-page":"708","DOI":"10.1016\/j.stem.2010.11.014","article-title":"TIM-3 is a promising target to selectively kill acute myeloid leukemia stem cells","volume":"7","author":"Kikushige","year":"2010","journal-title":"Cell Stem Cell."},{"key":"ref_91","first-page":"189","article-title":"CD38 in hematopoietic Malignancies","volume":"75","author":"Konopleva","year":"2000","journal-title":"Chem. Immunol."},{"key":"ref_92","doi-asserted-by":"crossref","first-page":"35707","DOI":"10.18632\/oncotarget.16060","article-title":"Targeting CD157 in AML using a novel, Fc-engineered antibody construct","volume":"8","author":"Krupka","year":"2017","journal-title":"Oncotarget"},{"key":"ref_93","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_94","doi-asserted-by":"crossref","first-page":"286","DOI":"10.1016\/j.cell.2009.05.045","article-title":"CD47 is an adverse prognostic factor and therapeutic antibody target on human acute myeloid leukemia stem cells","volume":"138","author":"Majeti","year":"2009","journal-title":"Cell"},{"key":"ref_95","doi-asserted-by":"crossref","first-page":"17ra9","DOI":"10.1126\/scitranslmed.3000349","article-title":"Identification of therapeutic targets for quiescent, chemotherapy-resistant human leukemia stem cells","volume":"2","author":"Saito","year":"2010","journal-title":"Sci. Transl. Med."},{"key":"ref_96","doi-asserted-by":"crossref","first-page":"3416","DOI":"10.1182\/blood-2024-205683","article-title":"CD64 CAR-T Therapy Targets Venetoclax-Resistant Monocytic Acute Myeloid Leukemia","volume":"144","author":"Simpson","year":"2024","journal-title":"Blood"},{"key":"ref_97","first-page":"1617","article-title":"Detailed analysis of FLT3 expression levels in acute myeloid leukemia","volume":"90","author":"Kuchenbauer","year":"2005","journal-title":"Haematologica"},{"key":"ref_98","doi-asserted-by":"crossref","first-page":"1675","DOI":"10.1038\/s43018-023-00656-2","article-title":"Systematic evaluation of AML-associated antigens identifies anti-U5 SNRNP200 therapeutic antibodies for the treatment of acute myeloid leukemia","volume":"4","author":"Knorr","year":"2023","journal-title":"Nat. Cancer"},{"key":"ref_99","doi-asserted-by":"crossref","unstructured":"Maiorova, V., Mollaev, M.D., Vikhreva, P., Kibardin, A., Maschan, M.A., and Larin, S.S. (2025). The Problem of Molecular Target Choice for CAR-T Cells in Acute Myeloid Leukemia Therapy. Int. J. Mol. Sci., 26.","DOI":"10.3390\/ijms26125428"},{"key":"ref_100","doi-asserted-by":"crossref","first-page":"21","DOI":"10.1007\/s44272-025-00050-2","article-title":"Advances in CAR-T cell therapy for refractory diseases: Challenges, innovations, clinical breakthroughs, and future prospects","volume":"4","author":"Liao","year":"2025","journal-title":"Clin. Cancer Bull."},{"key":"ref_101","doi-asserted-by":"crossref","first-page":"2676","DOI":"10.7150\/ijbs.108036","article-title":"From molecular design to clinical translation: Dual-targeted CAR-T strategies in cancer immunotherapy","volume":"21","author":"Wang","year":"2025","journal-title":"Int. J. Biol. Sci."},{"key":"ref_102","doi-asserted-by":"crossref","unstructured":"Tomai, R., Rivas, J.D.L., Fetica, B., Bergantim, R., Filipic, B., Gagic, Z., Nikolic, K., Gulei, D., Kegyes, D., and Nistor, M. (2025). Challenges in the preclinical design and assessment of CAR-T cells. Front. Immunol., 16.","DOI":"10.3389\/fimmu.2025.1564998"},{"key":"ref_103","doi-asserted-by":"crossref","unstructured":"Li, G., Li, D., and Zhu, X. (2025). Next-generation T cell immunotherapy: Overcoming exhaustion, senescence, and suppression. Front. Immunol., 16.","DOI":"10.3389\/fimmu.2025.1662145"},{"key":"ref_104","doi-asserted-by":"crossref","first-page":"3155","DOI":"10.1016\/j.ymthe.2022.06.006","article-title":"Universal allogeneic CAR T cells engineered with Sleeping Beauty transposons and CRISPR-CAS9 for cancer immunotherapy","volume":"30","author":"Tipanee","year":"2022","journal-title":"Mol. Ther."},{"key":"ref_105","doi-asserted-by":"crossref","first-page":"2764","DOI":"10.1158\/1078-0432.CCR-20-3863","article-title":"CRISPR\/Cas9-Engineered Universal CD19\/CD22 Dual-Targeted CAR-T Cell Therapy for Relapsed\/Refractory B-cell Acute Lymphoblastic Leukemia","volume":"27","author":"Hu","year":"2021","journal-title":"Clin. Cancer Res."},{"key":"ref_106","doi-asserted-by":"crossref","first-page":"8491","DOI":"10.1038\/s41467-023-44176-0","article-title":"Cyclosporine A-resistant CAR-T cells mediate antitumour immunity in the presence of allogeneic cells","volume":"14","author":"Zhang","year":"2023","journal-title":"Nat. Commun."},{"key":"ref_107","doi-asserted-by":"crossref","unstructured":"Shin, E., Bak, S.H., Park, T., Kim, J.W., Yoon, S.-R., Jung, H., and Noh, J.-Y. (2023). Understanding NK cell biology for harnessing NK cell therapies: Targeting cancer and beyond. Front. Immunol., 14.","DOI":"10.3389\/fimmu.2023.1192907"},{"key":"ref_108","doi-asserted-by":"crossref","unstructured":"Heipertz, E.L., Zynda, E.R., Stav-Noraas, T.E., Hungler, A.D., Boucher, S.E., Kaur, N., and Vemuri, M.C. (2021). Current perspectives on \u201cOff-the-shelf\u201d Allogeneic NK and CAR-NK cell therapies. Front. Immunol., 12.","DOI":"10.3389\/fimmu.2021.732135"},{"key":"ref_109","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_110","doi-asserted-by":"crossref","unstructured":"Zhang, C., Oberoi, P., Oelsner, S., Waldmann, A., Lindner, A., Tonn, T., and Wels, W.S. (2017). Chimeric antigen receptor-engineered NK-92 cells: An off-the-shelf cellular therapeutic for targeted elimination of cancer cells and induction of protective antitumor immunity. Front. Immunol., 8.","DOI":"10.3389\/fimmu.2017.00533"},{"key":"ref_111","doi-asserted-by":"crossref","first-page":"1089","DOI":"10.1038\/s41423-024-01207-0","article-title":"CAR-T and CAR-NK as cellular cancer immunotherapy for solid tumors","volume":"21","author":"Peng","year":"2024","journal-title":"Cell. Mol. Immunol."},{"key":"ref_112","doi-asserted-by":"crossref","first-page":"e18369","DOI":"10.1111\/jcmm.18369","article-title":"Recent advances in CAR-T cell therapy for acute myeloid leukaemia","volume":"28","author":"Gao","year":"2024","journal-title":"J. Cell. Mol. Med."},{"key":"ref_113","doi-asserted-by":"crossref","unstructured":"Cao, L.Y., Zhao, Y., Chen, Y., Ma, P., Xie, J.C., Pan, X.M., Zhang, X., Chen, Y.C., Wang, Q., and Xie, L.L. (2025). CAR-T cell therapy clinical trials: Global progress, challenges, and future directions from ClinicalTrials.gov insights. Front. Immunol., 16.","DOI":"10.3389\/fimmu.2025.1583116"},{"key":"ref_114","doi-asserted-by":"crossref","first-page":"8323592","DOI":"10.1155\/2019\/8323592","article-title":"Targeting Leukemia Stem Cell-Niche Dynamics: A New Challenge in AML Treatment","volume":"2019","author":"Bernasconi","year":"2019","journal-title":"J. Oncol."},{"key":"ref_115","doi-asserted-by":"crossref","first-page":"3478","DOI":"10.1182\/blood-2024-201457","article-title":"Innovative Bone Marrow CAR-T Cell Manufacturing for AML: Enhancing Viability and Tumor Migration","volume":"144","author":"Garcia","year":"2024","journal-title":"Blood"},{"key":"ref_116","doi-asserted-by":"crossref","first-page":"114421","DOI":"10.1016\/j.addr.2022.114421","article-title":"Cellular kinetics: A clinical and computational review of CAR-T cell pharmacology","volume":"188","author":"Qi","year":"2022","journal-title":"Adv. Drug Deliv. Rev."},{"key":"ref_117","doi-asserted-by":"crossref","unstructured":"Alnefaie, A., Albogami, S., Asiri, Y., Ahmad, T., Alotaibi, S.S., Al-Sanea, M.M., and Althobaiti, H. (2022). Chimeric Antigen Receptor T-Cells: An Overview of Concepts, Applications, Limitations, and Proposed Solutions. Front. Bioeng. Biotechnol., 10.","DOI":"10.3389\/fbioe.2022.797440"},{"key":"ref_118","doi-asserted-by":"crossref","first-page":"304","DOI":"10.1186\/s12935-024-03479-y","article-title":"Recent updates on allogeneic CAR-T cells in hematological malignancies","volume":"24","author":"Mansoori","year":"2024","journal-title":"Cancer Cell Int."},{"key":"ref_119","doi-asserted-by":"crossref","unstructured":"Medina-Olivares, F.J., G\u00f3mez-De Le\u00f3n, A., and Ghosh, N. (2024). Obstacles to global implementation of CAR T cell therapy in myeloma and lymphoma. Front. Oncol., 14.","DOI":"10.3389\/fonc.2024.1397613"},{"key":"ref_120","doi-asserted-by":"crossref","unstructured":"P\u00e9rez-Amill, L., Bataller, \u00c0., Delgado, J., Esteve, J., Juan, M., and Klein-Gonz\u00e1lez, N. (2023). Advancing CART therapy for acute myeloid leukemia: Recent breakthroughs and strategies for future development. Front. Immunol., 14.","DOI":"10.3389\/fimmu.2023.1260470"},{"key":"ref_121","doi-asserted-by":"crossref","unstructured":"Guijarro-Albaladejo, B., Marrero-Cepeda, C., Rodr\u00edguez-Arbol\u00ed, E., Sierro-Mart\u00ednez, B., P\u00e9rez-Sim\u00f3n, J.A., and Garc\u00eda-Guerrero, E. (2024). Chimeric antigen receptor (CAR) modified T Cells in acute myeloid leukemia: Limitations and expectations. Front. Cell Dev. Biol., 12.","DOI":"10.3389\/fcell.2024.1376554"},{"key":"ref_122","doi-asserted-by":"crossref","first-page":"1656","DOI":"10.3324\/haematol.2023.283817","article-title":"Chimeric antigen receptor T-cell therapy in childhood acute myeloid leukemia: How far are we from a clinical application?","volume":"109","author":"Naik","year":"2024","journal-title":"Haematologica"},{"key":"ref_123","doi-asserted-by":"crossref","first-page":"101566","DOI":"10.1016\/j.beha.2024.101566","article-title":"Allogeneic \u201cOff-the-Shelf\u201d CAR T cells: Challenges and advances","volume":"37","author":"Chen","year":"2024","journal-title":"Best Pract. Res. Clin. Haematol."},{"key":"ref_124","doi-asserted-by":"crossref","first-page":"17","DOI":"10.1016\/j.omtm.2022.08.008","article-title":"Applying a clinical lens to animal models of CAR-T cell therapies","volume":"27","author":"Duncan","year":"2022","journal-title":"Mol. Ther. Methods Clin. Dev."},{"key":"ref_125","doi-asserted-by":"crossref","first-page":"189455","DOI":"10.1016\/j.bbcan.2025.189455","article-title":"Animal models in preclinical evaluation of CAR-T cell therapy: Advantages and limitations","volume":"1880","author":"Pedersen","year":"2025","journal-title":"Biochim. Biophys. Acta Rev. Cancer"},{"key":"ref_126","doi-asserted-by":"crossref","first-page":"3","DOI":"10.1002\/ame2.12353","article-title":"Progress, implications, and challenges in using humanized immune system mice in CAR-T therapy-Application evaluation and improvement","volume":"7","author":"Yue","year":"2024","journal-title":"Anim. Model. Exp. Med."},{"key":"ref_127","doi-asserted-by":"crossref","unstructured":"Damiani, D., and Tiribelli, M. (2024). Advancing Chimeric Antigen Receptor T-Cell Therapy for Acute Myeloid Leukemia: Current Limitations and Emerging Strategies. Pharmaceuticals, 17.","DOI":"10.3390\/ph17121629"},{"key":"ref_128","doi-asserted-by":"crossref","unstructured":"Rozenbaum, M., Meir, A., Aharony, Y., Itzhaki, O., Schachter, J., Bank, I., Jacoby, E., and Besser, M.J. (2020). Gamma-Delta CAR-T Cells Show CAR-Directed and Independent Activity Against Leukemia. Front. Immunol., 11.","DOI":"10.3389\/fimmu.2020.01347"},{"key":"ref_129","doi-asserted-by":"crossref","unstructured":"Ma, L., Feng, Y., and Zhou, Z. (2023). A close look at current \u03b3\u03b4 T-cell immunotherapy. Front. Immunol., 14.","DOI":"10.3389\/fimmu.2023.1140623"},{"key":"ref_130","doi-asserted-by":"crossref","unstructured":"Fang, Y., Zhu, Y., Kramer, A., Chen, Y., Li, Y.R., and Yang, L. (2023). Graft-versus-Host Disease Modulation by Innate T Cells. Int. J. Mol. Sci., 24.","DOI":"10.3390\/ijms24044084"},{"key":"ref_131","doi-asserted-by":"crossref","unstructured":"Dos Reis, F.D., Saidani, Y., Mart\u00edn-Rubio, P., Sanz-Pamplona, R., Stojanovic, A., and Correia, M.P. (2025). CAR-NK cells: Harnessing the power of natural killers for advanced cancer therapy. Front. Immunol., 16.","DOI":"10.3389\/fimmu.2025.1603757"},{"key":"ref_132","doi-asserted-by":"crossref","unstructured":"Goldenson, B.H., Zhu, H., Wang, Y.M., Heragu, N., Bernareggi, D., Ruiz-Cisneros, A., Bahena, A., Ask, E.H., Hoel, H.J., and Malmberg, K.J. (2020). Umbilical Cord Blood and iPSC-Derived Natural Killer Cells Demonstrate Key Differences in Cytotoxic Activity and KIR Profiles. Front. Immunol., 11.","DOI":"10.3389\/fimmu.2020.561553"},{"key":"ref_133","doi-asserted-by":"crossref","first-page":"811","DOI":"10.3727\/096504020X15965357399750","article-title":"Outcomes of Patients with Acute Myeloid Leukemia Who Relapse After 5 Years of Complete Remission","volume":"28","author":"Patel","year":"2021","journal-title":"Oncol. Res."},{"key":"ref_134","doi-asserted-by":"crossref","first-page":"729","DOI":"10.1016\/j.clml.2019.08.007","article-title":"Impact of Time Between Induction Chemotherapy and Complete Remission on Survival Outcomes in Patients withAcute Myeloid Leukemia","volume":"19","author":"Ciftciler","year":"2019","journal-title":"Clin. Lymphoma Myeloma Leuk."},{"key":"ref_135","doi-asserted-by":"crossref","first-page":"337","DOI":"10.1182\/bloodadvances.2023011992","article-title":"Early predictive factors of failure in autologous CAR T-cell manufacturing and\/or efficacy in hematologic malignancies","volume":"8","author":"Baguet","year":"2024","journal-title":"Blood Adv."},{"key":"ref_136","doi-asserted-by":"crossref","unstructured":"Brezinger-Dayan, K., Itzhaki, O., Melnichenko, J., Kubi, A., Zeltzer, L.A., Jacoby, E., Avigdor, A., Shapira Frommer, R., and Besser, M.J. (2022). Impact of cryopreservation on CAR T production and clinical response. Front. Oncol., 12.","DOI":"10.3389\/fonc.2022.1024362"},{"key":"ref_137","doi-asserted-by":"crossref","first-page":"995","DOI":"10.1182\/blood.2024027442","article-title":"CD7 CAR-T: A bridge to transplant in AML","volume":"145","author":"Mamonkin","year":"2025","journal-title":"Blood"},{"key":"ref_138","first-page":"e1980","article-title":"Healthcare cost and utilization for chimeric antigen receptor (CAR) T-cell therapy in the treatment of pediatric acute lymphoblastic leukemia: A commercial insurance claims database analysis","volume":"7","author":"Hoover","year":"2024","journal-title":"Cancer Rep."},{"key":"ref_139","doi-asserted-by":"crossref","first-page":"e397912","DOI":"10.1200\/EDBK_397912","article-title":"High Cost of Chimeric Antigen Receptor T-Cells: Challenges and Solutions","volume":"43","author":"Cliff","year":"2023","journal-title":"Am. Soc. Clin. Oncol. Educ. Book"},{"key":"ref_140","doi-asserted-by":"crossref","first-page":"2483613","DOI":"10.1080\/20565623.2025.2483613","article-title":"CAR-T cell therapies: Patient access and affordability solutions","volume":"11","year":"2025","journal-title":"Future Sci. OA"},{"key":"ref_141","doi-asserted-by":"crossref","first-page":"1149","DOI":"10.1016\/j.jval.2024.04.004","article-title":"Economic Evaluations of Chimeric Antigen Receptor T-Cell Therapies for Hematologic and Solid Malignancies: A Systematic Review","volume":"27","author":"Thavorn","year":"2024","journal-title":"Value Health"},{"key":"ref_142","doi-asserted-by":"crossref","first-page":"200980","DOI":"10.1016\/j.omton.2025.200980","article-title":"Cost-effective strategies for CAR-T cell therapy manufacturing","volume":"33","author":"Abdo","year":"2025","journal-title":"Mol. Ther. Oncol."},{"key":"ref_143","doi-asserted-by":"crossref","first-page":"S253","DOI":"10.37765\/ajmc.2021.88737","article-title":"Improving outcomes and mitigating costs associated with CAR T-cell therapy","volume":"27","author":"Borgert","year":"2021","journal-title":"Am. J. Manag. 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