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利用 NK 细胞治疗多发性骨髓瘤

英文原题:Harnessing natural killer cells for the treatment of multiple myeloma.

查看英文原题

Harnessing natural killer cells for the treatment of multiple myeloma.

PubMed 2022/01/21(内容时间) Semin Oncol Q1 · IF 6.8(JCR 2025)

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中文摘要

多发性骨髓瘤(MM)是一种与显著免疫改变相关的血液系统恶性肿瘤。骨髓瘤细胞容易被自然杀伤(NK)细胞杀伤,但会通过逃避识别和抑制NK细胞功能来获得逃逸NK细胞监视的能力。通过重新定向NK细胞并增强其功能的新药,MM治疗取得了重大进展。尽管进步显著,骨髓瘤仍无法治愈,仍需新的治疗方法。利用NK细胞固有抗肿瘤特性治疗MM,是一种新型免疫治疗策略。其中一种方法是过继NK细胞疗法,即输注体外扩增的NK细胞。过继NK细胞疗法涵盖现代基因工程策略,例如嵌合抗原受体(CAR)工程化NK细胞。另一种方法是使用药理学药物增强NK细胞对骨髓瘤的活性。调节NK细胞的疗法可增强内源性NK细胞功能,或提高过继输入NK细胞的疗效。本文综述影响MM中NK细胞活性的复杂机制,并介绍正在开发的多种创新型NK细胞治疗策略。

展开英文摘要原文

Multiple myeloma (MM) is hematologic malignancy that is associated with profound immune alterations. Myeloma cells are susceptible to killing by natural killer (NK) cells but acquire the ability to elude NK cell surveillance by avoiding recognition and suppressing NK cell function. Major advances in the treatment of multiple myeloma have been achieved by effective new drugs that redirect NK cells and enhance their function. Despite significant progress, myeloma remains incurable and novel treatment approaches are required.

Strategies to take advantage of the intrinsic antitumor properties of NK cells to treat MM represent a novel immunotherapeutic approach. One such strategy is adoptive NK cell therapy that consist of infusions of NK cells that have been propagated ex vivo. Adoptive NK cell therapy encompasses contemporary genetic engineering strategies such as chimeric antigen receptor (CAR)-engineered NK cells.

An alternative approach involves the use of pharmacologic agents to enhance NK cell activity against myeloma. NK cell-modulating therapies can be used to bolster the function of endogenous NK cells or to enhance the efficacy of adoptively infused NK cells.

Here, we review the mechanistic complexities influencing NK cell activity in MM and highlight a variety of innovative NK cell-based strategies being developed for the treatment of MM.

论文信息

作者
Clara JA、Childs RW
单位
National Heart Lung and Blood Institute, National Institutes of Health, Bethesda, MD. Electronic address: joseph.clara@nih.gov.United States
文献类型
综述
期刊
Seminars in oncology2022 Feb
原文标识
PubMed 35125241 · DOI 10.1053/j.seminoncol.2022.01.004