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释放 CAR-NK 细胞治疗潜力:克服髓系恶性肿瘤治疗中的障碍与挑战

英文原题:Unlocking the Potential of CAR-NK Cell Therapy: Overcoming Barriers and Challenges in the Treatment of Myeloid Malignancies.

查看英文原题

Unlocking the Potential of CAR-NK Cell Therapy: Overcoming Barriers and Challenges in the Treatment of Myeloid Malignancies.

PubMed 2025/04/02(内容时间) Mol Cancer Ther Q1 · IF 6.9(JCR 2025)

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中文摘要

髓系恶性肿瘤包括多种源于骨髓内髓系细胞异常发育或增殖的癌症。嵌合抗原受体(CAR)T细胞治疗在B细胞和浆细胞癌症中展现出巨大潜力,但用于髓系恶性肿瘤时面临重大挑战。基于CAR自然杀伤(NK)细胞的免疫治疗在治疗髓系癌症时遇到若干挑战,包括(i)体外基因转移效率和扩增平台不佳,(ii)体内增殖和持久性有限,(iii)抗原异质性,以及(iv)免疫抑制性肿瘤微环境。尽管存在这些障碍,“现货型”CAR-NK治疗仍显示出令人鼓舞的结果,表现为增殖增强、持久性延长、肿瘤浸润增强和适应性改善。本综述总结了NK细胞的生物学特征和细胞来源,并讨论了当代CAR设计。此外,还探讨了与CAR-NK细胞治疗髓系癌症相关的临床前研究和临床试验中观察到的挑战,并提出了增强策略。

展开英文摘要原文

Myeloid malignancies include various types of cancers that arise from the abnormal development or proliferation of myeloid cells within the bone marrow. Chimeric antigen receptor (CAR) T cell treatments, which show great potential for B cell and plasma cell cancers, face major challenges when used for myeloid malignancies. CAR natural killer (NK) cell-based immunotherapy encounters several challenges in treating myeloid cancers, including (i) poor gene transfer efficiency and expansion platforms in vitro, (ii) limited proliferation and persistence in vivo, (iii) antigenic heterogeneity, and (iv) an immunosuppressive tumor microenvironment.

Despite these hurdles, "off-the-shelf" CAR-NK treatments showed encouraging results, marked by enhanced proliferation, prolonged persistence, enhanced tumor infiltration, and improved adaptability. This review offers a summary of the biological traits and cellular sources of NK cells along with a discussion of contemporary CAR designs.

Furthermore, it addresses the challenges observed in preclinical research and clinical trials related to CAR-NK cell therapy for myeloid cancers, suggesting enhancement strategies.

论文信息

作者
Zhang A、Yang X、Zhang Y、Yu X、Mu W、Wei J
单位
Department of Hematology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.China
文献类型
综述
期刊
Molecular cancer therapeutics2025 Apr 2
原文标识
PubMed 39834301 · DOI 10.1158/1535-7163.MCT-24-0721