Damiani Daniela, Tiribelli Mario
Division of Hematology and Stem Cell Transplantation, University Hospital, 33100 Udine, Italy.
Department of Medicine (DMED), University of Udine, 33100 Udine, Italy.
Pharmaceuticals (Basel). 2024 Dec 4;17(12):1629. doi: 10.3390/ph17121629.
Chimeric antigen receptor (CAR) T-cell therapy represents one of the most impressive advances in anticancer therapy of the last decade. While CAR T-cells are gaining ground in various B cell malignancies, their use in acute myeloid leukemia (AML) remains limited, and no CAR-T product has yet received approval for AML. The main limitation of CAR-T therapy in AML is the lack of specific antigens that are expressed in leukemic cells but not in their healthy counterparts, such as hematopoietic stem cells (HSCs), as their targeting would result in an on-target/off-tumor toxicity. Moreover, the heterogeneity of AML and the tendency of blasts to modify surface antigens' expression in the course of the disease make identification of suitable targets even more challenging. Lastly, AML's immunosuppressive microenvironment dampens CAR-T therapeutic activities. In this review, we focus on the actual pitfalls of CAR T-cell therapy in AML, and we discuss promising approaches to overcome them.
嵌合抗原受体（CAR）T细胞疗法是过去十年抗癌治疗中最引人注目的进展之一。虽然CAR T细胞在各种B细胞恶性肿瘤中逐渐获得认可，但它们在急性髓系白血病（AML）中的应用仍然有限，且尚无CAR-T产品获批用于AML治疗。CAR-T疗法在AML中的主要局限性在于缺乏在白血病细胞而非其健康对应细胞（如造血干细胞（HSCs））中表达的特异性抗原，因为靶向这些抗原会导致靶向肿瘤外毒性。此外，AML的异质性以及原始细胞在疾病过程中改变表面抗原表达的趋势使得确定合适的靶点更具挑战性。最后，AML的免疫抑制微环境会抑制CAR-T的治疗活性。在这篇综述中，我们重点关注CAR T细胞疗法在AML中实际存在的缺陷，并讨论克服这些缺陷的有前景的方法。
