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塑造骨髓增殖性肿瘤治疗的未来:免疫策略与靶向创新

英文原题:Shaping the Future of Myeloproliferative Neoplasm Therapy: Immune-Based Strategies and Targeted Innovations.

查看英文原题

Shaping the Future of Myeloproliferative Neoplasm Therapy: Immune-Based Strategies and Targeted Innovations.

PubMed 2024/12/08(内容时间) Cancers (Basel) Q2 · IF 4.8(JCR 2025)

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中文摘要

血液系统恶性肿瘤已开发多种前沿免疫治疗,例如淋巴瘤免疫检查点抑制剂、治疗B细胞癌的嵌合抗原受体(CAR)T细胞疗法,以及治疗急性髓系白血病(AML)的单克隆抗体。然而,骨髓增殖性肿瘤(MPN)领域难以取得类似突破。主要障碍包括缺乏普遍表达且MPN特异的细胞表面标志物、不同患者及不同MPN亚型之间存在显著细胞和分子差异,以及髓系肿瘤造成免疫系统功能紊乱,使治疗无法激发抗肿瘤免疫应答。目前多种创新疗法正在MPN临床试验中评估,包括对JAK2特异性更强的新型JAK抑制剂,以及用于初治或对芦可替尼应答不理想患者、旨在增强芦可替尼疗效的“附加”药物。此外,研究者也在探索新型治疗靶点。本综述探讨MPN目前临床使用的免疫治疗方法及新兴策略,这些策略可能在未来几年改变MPN治疗。

展开英文摘要原文

Numerous cutting-edge immunotherapy approaches have been developed for hematological malignancies, such as immune-checkpoint inhibitors for lymphomas, chimeric antigen receptor (CAR)-T-cell treatments for B-cell cancers, and monoclonal antibody therapies for acute myeloid leukemia (AML).

However, achieving similar breakthroughs in MPNs has proven challenging. The key obstacles include the absence of universally expressed and MPN-specific surface markers, significant cellular and molecular variability among both individual patients and across different MPN subtypes, and the failure of treatments to stimulate an anti-tumor immune response due to the immune system disruptions caused by the myeloid neoplasm.

Currently, there are several innovative therapies in clinical trials for MPNs. These include new JAK inhibitors with greater specificity for JAK2, as well as "add-on" medications designed to enhance the effectiveness of ruxolitinib, in both patients who are new to the drug and in those who have shown suboptimal responses.

Additionally, there is ongoing exploration of novel therapeutic targets. In this review, we will explore the immunotherapy approaches that are currently used in clinical practice for MPNs, as well as emerging strategies that are likely to change the treatment of these diseases in the coming years.

论文信息

作者
Carturan A、Morè S、Poloni A、Rupoli S、Morsia E
第一作者单位
Center for Cellular Immunotherapies, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, PA 19104, USA.United States
通讯作者单位
Department of Clinical and Molecular Sciences (DISCLIMO), Università Politecnica delle Marche, 60126 Ancona, Italy.Italy
文献类型
综述
期刊
Cancers2024 Dec 8
原文标识
PubMed 39682299 · DOI 10.3390/cancers16234113