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引用次数: 0
摘要
尽管在淋巴恶性肿瘤中取得了成功,但针对急性髓细胞白血病的采用性细胞疗法的努力基本上没有成果。鉴别白血病细胞上的可靶向抗原(正常祖细胞上没有)仍然是一个主要障碍,而急性髓细胞性白血病血块所造成的恶劣肿瘤微环境也是一个主要障碍。在这篇综述中,我们总结了在急性髓细胞性白血病中开发 CAR-T、CAR-NK 和 TCR-T 细胞等采纳性细胞疗法所面临的挑战,并讨论了自体和异体疗法。我们还讨论了解决与这些疗法相关的骨髓毒性的方法,包括可快速切换的 CAR 平台和 CRISPR-Cas9 造血干细胞基因工程。最后,我们介绍了这些领域目前的临床情况以及该领域未来的发展方向。
Adoptive cell therapy in acute myeloid leukemia: the current landscape and emerging strategies.
Efforts to produce adoptive cell therapies in AML have been largely unfruitful, despite the success seen in lymphoid malignancies. Identifying targetable antigens on leukemic cells that are absent on normal progenitor cells remains a major obstacle, as is the hostile tumor microenvironment created by AML blasts. In this review, we summarize the challenges in the development of adoptive cell therapies such as CAR-T, CAR-NK, and TCR-T cells in AML, discussing both autologous and allogeneic therapies. We also discuss methods to address myelotoxicity associated with these therapies, including rapidly switchable CAR platforms and CRISPR-Cas9 genetic engineering of hematopoietic stem cells. Finally, we present the current clinical landscape in these areas, along with future directions in the field.
期刊介绍:
Leukemia & Lymphoma in its fourth decade continues to provide an international forum for publication of high quality clinical, translational, and basic science research, and original observations relating to all aspects of hematological malignancies. The scope ranges from clinical and clinico-pathological investigations to fundamental research in disease biology, mechanisms of action of novel agents, development of combination chemotherapy, pharmacology and pharmacogenomics as well as ethics and epidemiology. Submissions of unique clinical observations or confirmatory studies are considered and published as Letters to the Editor