Tharakan Serena, Tremblay Douglas, Azzi Jacques
Department of Internal Medicine, Icahn School of Medicine at Mount Sinai, New York, NY, USA.
Tisch Cancer Institute, Icahn School of Medicine at Mount Sinai, New York, NY, USA.
Leuk Lymphoma. 2025 Feb;66(2):204-217. doi: 10.1080/10428194.2024.2414112. Epub 2024 Oct 25.
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.
尽管在淋巴系统恶性肿瘤治疗中取得了成功,但在急性髓系白血病(AML)中生产过继性细胞疗法的努力大多没有成效。识别正常祖细胞中不存在的白血病细胞上的可靶向抗原仍然是一个主要障碍,AML原始细胞所创造的恶劣肿瘤微环境也是如此。在这篇综述中,我们总结了AML中过继性细胞疗法(如CAR-T、CAR-NK和TCR-T细胞)发展面临的挑战,讨论了自体和异体疗法。我们还讨论了应对与这些疗法相关的骨髓毒性的方法,包括快速可切换的CAR平台和造血干细胞的CRISPR-Cas9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的未来发展方向。