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嵌合抗原受体 T 细胞疗法治疗急性髓系白血病。

CAR T-cell therapy in acute myeloid leukemia.

机构信息

From the Department of Clinical Laboratory Sciences, College of Applied Medical Sciences, Shaqra University, Shaqra, Kingdom of Saudi Arabia.

出版信息

Saudi Med J. 2024 Oct;45(10):1007-1019. doi: 10.15537/smj.2024.45.10.20240330.

Abstract

Acute myeloid leukemia (AML) is an aggressive leukemic malignancy that affects myeloid lineage progenitors. Relapsed or refractory AML patients continue to have poor prognoses, necessitating the development of novel therapy alternatives. Adoptive T-cell therapy with chimeric antigen receptors (CARs) is an intriguing possibility in the field of leukemia treatment. Chimeric antigen receptor T-cell therapy is now being tested in clinical trials (mostly in phase I and phase II) using AML targets including CD33, CD123, and CLL-1. Preliminary data showed promising results. However, due to the cellular and molecular heterogeneity of AML and the co-expression of some AML targets on hematopoietic stem cells, these clinical investigations have shown substantial "on-target off-tumor" toxicities, indicating that more research is required. In this review, the latest significant breakthroughs in AML CAR T cell therapy are presented. Furthermore, the limitations of CAR T-cell technology and future directions to overcome these challenges are discussed.

摘要

急性髓系白血病(AML)是一种侵袭性的白血病恶性肿瘤,影响髓系祖细胞。复发或难治性 AML 患者的预后仍然较差,需要开发新的治疗选择。嵌合抗原受体(CAR)的过继性 T 细胞疗法是白血病治疗领域一个有趣的可能性。嵌合抗原受体 T 细胞疗法目前正在临床试验中进行测试(主要在 I 期和 II 期),使用 AML 靶点,包括 CD33、CD123 和 CLL-1。初步数据显示出有希望的结果。然而,由于 AML 的细胞和分子异质性以及一些 AML 靶点在造血干细胞上的共表达,这些临床研究显示出大量的“靶内脱靶”毒性,表明需要进一步研究。在这篇综述中,介绍了 AML CAR T 细胞治疗的最新重大突破。此外,还讨论了 CAR T 细胞技术的局限性以及克服这些挑战的未来方向。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1918/11463564/fa695bf1d837/SMJ-45-10-1007_1.jpg

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