Acute myeloid leukemia (AML) is a serious, life-threatening, and hardly curable hematological malignancy that affects the myeloid cell progenies and challenges patients of all ages but mostly occurs in adults. Although several therapies are available including chemotherapy, allogeneic hematopoietic stem cell transplantation (alloHSCT), and receptor-antagonist drugs, the 5-year survival of patients is quietly disappointing, less than 30%. alloHSCT is the major curative approach for AML with promising results but the treatment has severe adverse effects such as graft-versus-host disease (GVHD). Therefore, as an alternative, more efficient and less harmful immunotherapy-based approaches such as the adoptive transferring T cell therapy are in development for the treatment of AML. As such, chimeric antigen receptor (CAR) T cells are engineered T cells which have been developed in recent years as a breakthrough in cancer therapy. Interestingly, CAR T cells are effective against both solid tumors and hematological cancers such as AML. Gradually, CAR T cell therapy found its way into cancer therapy and was widely used for the treatment of hematologic malignancies with successful results particularly with somewhat better results in hematological cancer in comparison to solid tumors. The AML is generally fatal, therapy-resistant, and sometimes refractory disease with a disappointing low survival rate and weak prognosis. The 5-year survival rate for AML is only about 30%. However, the survival rate seems to be age-dependent. Novel CAR T cell therapy is a light at the end of the tunnel. The CD19 is an important target antigen in AML and lymphoma and the CAR T cells are engineered to target the CD19. In addition, a lot of research goes on the discovery of novel target antigens with therapeutic efficacy and utilizable for generating CAR T cells against various types of cancers. In recent years, many pieces of research on screening and identification of novel AML antigen targets with the goal of generation of effective anti-cancer CAR T cells have led to new therapies with strong cytotoxicity against cancerous cells and impressive clinical outcomes. Also, more recently, an improved version of CAR T cells which were called modified or smartly reprogrammed CAR T cells has been designed with less unwelcome effects, less toxicity against normal cells, more safety, more specificity, longer persistence, and proliferation capability. The purpose of this review is to discuss and explain the most recent advances in CAR T cell-based therapies targeting AML antigens and review the results of preclinical and clinical trials. Moreover, we will criticize the clinical challenges, side effects, and the different strategies for CAR T cell therapy.

中文翻译：

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新型 CAR T 疗法为重症 AML 患者带来一线希望

急性髓性白血病 (AML) 是一种严重、危及生命且难以治愈的血液恶性肿瘤，它会影响骨髓细胞后代，并对所有年龄段的患者提出挑战，但主要发生在成人中。尽管有多种疗法可用，包括化学疗法、同种异体造血干细胞移植 (alloHSCT) 和受体拮抗剂药物，但患者的 5 年生存率令人失望，不到 30%。alloHSCT 是 AML 的主要治疗方法，具有可喜的结果，但该治疗具有严重的副作用，例如移植物抗宿主病 (GVHD)。因此，作为替代方案，正在开发用于治疗 AML 的更有效且危害更小的基于免疫疗法的方法，例如过继转移 T 细胞疗法。像这样，嵌合抗原受体 (CAR) T 细胞是近年来开发的工程化 T 细胞，作为癌症治疗的突破。有趣的是，CAR T 细胞对实体瘤和血液癌症（如 AML）均有效。渐渐地，CAR T 细胞疗法进入了癌症治疗领域，并被广泛用于治疗血液系统恶性肿瘤，并取得了成功的结果，尤其是与实体瘤相比，血液系统癌症的治疗效果更好。AML 通常是致命的、治疗耐药的，有时是难治性的疾病，具有令人失望的低存活率和较差的预后。AML 的 5 年生存率仅为 30% 左右。然而，存活率似乎与年龄有关。新型 CAR T 细胞疗法是隧道尽头的一盏灯。CD19 是 AML 和淋巴瘤中的重要靶抗原，CAR T 细胞被设计为靶向 CD19。此外，大量研究致力于发现具有治疗功效并可用于生成针对各种类型癌症的 CAR T 细胞的新型靶抗原。近年来，许多以产生有效抗癌CAR T细胞为目标的筛选和鉴定新型AML抗原靶点的研究已经产生了对癌细胞具有强细胞毒性和令人印象深刻的临床结果的新疗法。此外，最近，CAR T 细胞的改进版本被称为改良或智能重新编程的 CAR T 细胞，其设计具有更少的不良影响、对正常细胞的毒性更小、更安全、更特异性、更长的持久性和增殖能力。本综述的目的是讨论和解释针对 AML 抗原的 CAR T 细胞疗法的最新进展，并回顾临床前和临床试验的结果。此外，我们将批评 CAR T 细胞疗法的临床挑战、副作用和不同策略。