Garg Swati, Ni Wei, Griffin James D, Sattler Martin
Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, MA 02215, USA.
Department of Medicine, Harvard Medical School, Boston, MA 02115, USA.
Hematol Rep. 2023 Nov 12;15(4):608-626. doi: 10.3390/hematolrep15040063.
Acute myeloid leukemia (AML) is a heterogeneous hematological malignancy that is often associated with relapse and drug resistance after standard chemotherapy or targeted therapy, particularly in older patients. Hematopoietic stem cell transplants are looked upon as the ultimate salvage option with curative intent. Adoptive cell therapy using chimeric antigen receptors (CAR) has shown promise in B cell malignancies and is now being investigated in AML. Initial clinical trials have been disappointing in AML, and we review current strategies to improve efficacy for CAR approaches. The extensive number of clinical trials targeting different antigens likely reflects the genetic heterogeneity of AML. The limited number of patients reported in multiple early clinical studies makes it difficult to draw conclusions about CAR safety, but it does suggest that the efficacy of this approach in AML lags behind the success observed in B cell malignancies. There is a clear need not only to improve CAR design but also to identify targets in AML that show limited expression in normal myeloid lineage cells.
急性髓系白血病（AML）是一种异质性血液系统恶性肿瘤，在接受标准化疗或靶向治疗后常出现复发和耐药，在老年患者中尤为如此。造血干细胞移植被视为具有治愈意图的最终挽救选择。使用嵌合抗原受体（CAR）的过继性细胞疗法在B细胞恶性肿瘤中已显示出前景，目前正在AML中进行研究。AML的初步临床试验结果令人失望，我们回顾了当前提高CAR疗法疗效的策略。针对不同抗原的大量临床试验可能反映了AML的基因异质性。多项早期临床研究报告的患者数量有限，难以就CAR的安全性得出结论，但这确实表明该方法在AML中的疗效落后于在B细胞恶性肿瘤中观察到的成功。显然不仅需要改进CAR设计，还需要在AML中识别在正常髓系细胞谱系中表达有限的靶点。
