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CAR-T 细胞治疗急性髓系白血病:进展与结局

英文原题:CAR-T cell therapy for treatment of acute myeloid leukemia, advances and outcomes.

查看英文原题

CAR-T cell therapy for treatment of acute myeloid leukemia, advances and outcomes.

PubMed 2025/04/02(内容时间) Mol Ther Q1 · IF 11.4(JCR 2025)

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中文摘要

尽管美国食品药品监督管理局(FDA)近期批准多种急性髓系白血病(AML)疗法,患者临床结局仍然不佳。AML 有效免疫治疗方式很少,例如异基因干细胞移植;其部分原因是缺乏已知的 AML 特异性抗原,因为许多候选抗原也存在于重要正常造血前体细胞上。此外,AML 受到不利骨髓肿瘤微环境支持,该环境显著抑制 T 细胞效应功能。骨髓来源抑制细胞和调节性 T 细胞在 AML 微环境对内源性 T 细胞和过继转移 T 细胞产生免疫抑制方面发挥关键作用。目前有多项临床试验旨在检验过继转移 T 细胞(包括 CAR-T 细胞疗法)治疗 AML 的可行性和疗效,但尚无疗法获 FDA 批准用于这一致死性疾病。本综述剖析这些试验,阐述其对该治疗方向的贡献及取得的成功。

展开英文摘要原文

Despite recent U. S. Food and Drug Administration (FDA) approval of multiple therapies for patients with acute myeloid leukemia (AML), clinical outcomes for those patients continue to remain poor. There are very few effective immunotherapeutic modalities such as allogeneic stem cell transplant for AML, and this is, in part, due to a lack of known antigens that are unique to AML and not present on vital normal hematopoietic precursors.

Additionally, AML is supported by a hostile marrow tumor microenvironment that has a notable role in dampening T cell effector function. Myeloid-derived suppressor cells and regulatory T cells play a pivotal role in AML microenvironment immune hostility toward endogenous T cells as well as adoptively transferred T cells.

There are many clinical trials that are designed to test the feasibility and efficacy of adoptively transferred T cells, including chimeric antigen receptor T cell therapies in AML, yet none is FDA approved for this fatal disease. In this review, we dissect these trials, their contribution to this therapeutic direction, and their success.

论文信息

作者
Khalifeh M、Hopewell E、Salman H
第一作者单位
Brown Center for Immunotherapy, 975W. Walnut St., IB554A, Indianapolis, IN 46202, USA.Italy
通讯作者单位
Indiana University School of Medicine, Indianapolis, IN 46202, USA. Electronic address: hsalman@iu.edu.Italy
文献类型
综述
期刊
Molecular therapy : the journal of the American Society of Gene Therapy2025 Jun 4
原文标识
PubMed 40181544 · DOI 10.1016/j.ymthe.2025.03.052