Alati Caterina, Pitea Martina, Molica Matteo, Rossi Marco, Alvaro Maria Eugenia, Porto Gaetana, Bilardi Erica, Utano Giovanna, Policastro Giorgia, Micò Maria Caterina, Marafioti Violetta, Martino Massimo
Hematology and Stem Cell Transplantation and Cellular Therapies Unit (CTMO), Department of Hemato-Oncology and Radiotherapy, Grande Ospedale Metropolitano "Bianchi-Melacrino-Morelli", 89133 Reggio Calabria, Italy.
Department of Hematology-Oncology, Azienda Universitaria Ospedaliera Renato Dulbecco, 88100 Catanzaro, Italy.
Cancers (Basel). 2025 Dec 29;18(1):107. doi: 10.3390/cancers18010107.
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.
急性髓系白血病（AML）是一种侵袭性癌症，进展迅速且复发率高，凸显了对有效治疗方法的迫切需求。尽管近期药物治疗和联合方案取得了进展，改善了治疗效果，但复发/难治性（R/R）AML的缓解率仍然较低，预后较差，生存期有限。缺乏有效的免疫疗法进一步使R/R AML的治疗复杂化。骨髓肿瘤微环境（TME）构成了重大障碍，需要多方面的联合治疗策略才能取得临床成功。这种TME创造了一个免疫抑制和代谢具有挑战性的环境，限制了嵌合抗原受体（CAR）T细胞的扩增、持久性、细胞毒性和存活。与B细胞急性淋巴细胞白血病（B-ALL）中的CD19不同，AML缺乏真正的白血病特异性抗原。尽管临床试验正在进行，但尚无CAR-T疗法获得FDA批准用于AML。本文探讨了这些持续存在的挑战背后的原因。
