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CAR-T 疗法在急性髓系白血病中是否有未来?

英文原题:Is There a Future for CAR-T Therapy in Acute Myeloid Leukemia?

查看英文原题

Is There a Future for CAR-T Therapy in Acute Myeloid Leukemia?

PubMed 2025/12/29(内容时间) Cancers (Basel) Q2 · IF 4.8(JCR 2025)

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中文摘要

急性髓系白血病(AML)是一种进展迅速、复发率高的侵袭性癌症,凸显了开发有效治疗的迫切需求。尽管近期药物治疗和联合方案进展改善了结局,复发/难治性(R/R)AML仍缓解率低、预后差、生存有限。缺乏有效免疫疗法进一步增加了R/R AML管理难度。骨髓肿瘤微环境(TME)构成显著障碍,临床成功需要多层次联合治疗策略。该TME形成免疫抑制且代谢不利的环境,限制嵌合抗原受体(CAR)T细胞扩增、持久性、细胞毒作用和存活。与B细胞急性淋巴细胞白血病(B-ALL)中的CD19不同,AML缺乏真正白血病特异性抗原。尽管临床试验仍在进行,目前尚无CAR-T 疗法获FDA批准用于AML。本文探讨这些持续挑战背后的原因。

展开英文摘要原文

Acute myeloid leukemia (AML) is an aggressive cancer with rapid progression and a high relapse rate, highlighting the urgent need for effective treatments. While recent advances in drug therapies and combination regimens have improved outcomes, relapsed and refractory (R/R) AML still shows low response rates, poor prognosis, and limited survival. The lack of effective immunotherapies further complicates the management of R/R AML. The bone marrow tumor microenvironment (TME) poses a significant barrier, requiring multifaceted, combined therapeutic strategies for clinical success.

This TME creates an immunosuppressive and metabolically challenging environment that limits the expansion, persistence, cytotoxicity, and survival of chimeric antigen receptor (CAR) T cells. Unlike CD19 in B-cell acute lymphoblastic leukemia (B-ALL), AML lacks a truly leukemia-specific antigen. Although clinical trials are ongoing, no CAR-T therapies have received FDA approval for AML. This paper explores the reasons behind these ongoing challenges.

论文信息

作者
Alati C、Pitea M、Molica M、Rossi M、Alvaro ME、Porto G、Bilardi E、Utano G
单位
Hematology and Stem Cell Transplantation and Cellular Therapies Unit (CTMO), Department of Hemato-Oncology and Radiotherapy, Grande Ospedale Metropolitano "Bianchi-Melacrino-Morelli", 89133 Reggio Calabria, Italy.Italy
文献类型
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期刊
Cancers2025 Dec 29
原文标识
PubMed 41514619 · DOI 10.3390/cancers18010107