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Chimeric antigen receptor T-cell (CAR-T) therapy has emerged as a personalized cancer treatment, modifying patients\u2019 T cells to target and destroy resistant cancer cells. This study reviews the current therapeutic options of CAR-T therapy for leukemia, addressing the primary obstacles such as antigen escape and T-cell exhaustion. We explore dual-targeting strategies and their potential to improve treatment outcomes by preventing the loss of target antigens. Additionally, we examine the mechanisms of T-cell exhaustion and strategies to enhance CAR-T persistence and effectiveness. Despite remarkable clinical successes, CAR-T therapy poses risks such as cytokine release syndrome (CRS) and immune effector cell-associated neurotoxicity syndrome (ICANS). Our findings highlight the need for ongoing research to optimize CAR-T applications, reduce toxicities, and extend this innovative therapy to a broader range of hematologic malignancies. This comprehensive review aims to provide valuable insights for improving leukemia treatment and advancing the field of cancer immunotherapy.<\/jats:p>","DOI":"10.3390\/cells13181596","type":"journal-article","created":{"date-parts":[[2024,9,23]],"date-time":"2024-09-23T09:15:07Z","timestamp":1727082907000},"page":"1596","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":39,"title":["Overcoming Antigen Escape and T-Cell Exhaustion in CAR-T Therapy for Leukemia"],"prefix":"10.3390","volume":"13","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-7447-8248","authenticated-orcid":false,"given":"El\u017cbieta","family":"Bartoszewska","sequence":"first","affiliation":[{"name":"Faculty of Medicine, Wroclaw Medical University, Mikulicza-Radeckiego 5, 50-345 Wroclaw, Poland"},{"name":"Student Research Group No K148, Faculty of Pharmacy, Wroclaw Medical University, Borowska 211A, 50-556 Wroclaw, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5298-6479","authenticated-orcid":false,"given":"Maciej","family":"Tota","sequence":"additional","affiliation":[{"name":"Faculty of Medicine, Wroclaw Medical University, Mikulicza-Radeckiego 5, 50-345 Wroclaw, Poland"},{"name":"Student Research Group No K148, Faculty of Pharmacy, Wroclaw Medical University, Borowska 211A, 50-556 Wroclaw, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0002-8166-4353","authenticated-orcid":false,"given":"Monika","family":"Kisielewska","sequence":"additional","affiliation":[{"name":"Faculty of Medicine, Wroclaw Medical University, Mikulicza-Radeckiego 5, 50-345 Wroclaw, Poland"},{"name":"Student Research Group No K148, Faculty of Pharmacy, Wroclaw Medical University, Borowska 211A, 50-556 Wroclaw, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0000-2503-7473","authenticated-orcid":false,"given":"Izabela","family":"Skowron","sequence":"additional","affiliation":[{"name":"Faculty of Medicine, Wroclaw Medical University, Mikulicza-Radeckiego 5, 50-345 Wroclaw, Poland"},{"name":"Student Research Group No K148, Faculty of Pharmacy, Wroclaw Medical University, Borowska 211A, 50-556 Wroclaw, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0005-9248-5512","authenticated-orcid":false,"given":"Kamil","family":"Sebastianka","sequence":"additional","affiliation":[{"name":"Faculty of Medicine, Wroclaw Medical University, Mikulicza-Radeckiego 5, 50-345 Wroclaw, Poland"},{"name":"Student Research Group No K148, Faculty of Pharmacy, Wroclaw Medical University, Borowska 211A, 50-556 Wroclaw, 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Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0004-7902-5514","authenticated-orcid":false,"given":"Jakub","family":"Rubin","sequence":"additional","affiliation":[{"name":"Faculty of Medicine, Wroclaw Medical University, Mikulicza-Radeckiego 5, 50-345 Wroclaw, Poland"},{"name":"Student Research Group No K148, Faculty of Pharmacy, Wroclaw Medical University, Borowska 211A, 50-556 Wroclaw, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0008-0741-9679","authenticated-orcid":false,"given":"Karolina","family":"Kraska","sequence":"additional","affiliation":[{"name":"Faculty of Medicine, Wroclaw Medical University, Mikulicza-Radeckiego 5, 50-345 Wroclaw, Poland"},{"name":"Student Research Group No K148, Faculty of Pharmacy, Wroclaw Medical University, Borowska 211A, 50-556 Wroclaw, 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