肿瘤细胞治疗研究
英文原题：Natural Killer Cell-Derived Extracellular Vesicle Preparations Demonstrate Potent Antitumor Activity Against Human Glioblastoma In Vitro and In Vivo.
这些发现确立了NK-EVs作为一种有效的GBM无细胞免疫治疗策略，其有潜力规避过继性NK细胞治疗的关键局限性，包括免疫抑制性肿瘤微环境。
源自活化自然杀伤（NK）细胞的细胞外囊泡（EVs）是一种有前景的无细胞癌症免疫疗法。然而，利用原代扩增的人NK细胞来源的EVs（NK-EVs）治疗难治性脑肿瘤的研究仍不充分。在此，我们评估了常见的EV分离方法，包括用于获取大量EVs的沉淀法以及用于同时获取NK-EVs和蛋白质的尺寸排阻色谱法（SEC）。沉淀法获得的NK-EVs对多种胶质母细胞瘤（GBM）细胞系表现出强效的剂量依赖性细胞毒性，包括那些对常规NK细胞疗法耐药的细胞系。它们在皮下GBM异种移植模型中抑制了肿瘤生长，并且在静脉给药后，显著抑制了原位脑肿瘤的进展并延长了生存期。
Extracellular vesicles (EVs) derived from activated natural killer (NK) cells represent a promising cell-free immunotherapy for cancer. However, the use of primary expanded human NK cell-derived EVs (NK-EVs) for intractable brain tumours is underexplored. Here, we evaluated common EV isolation methods including precipitation for bulk EVs and size exclusion chromatography (SEC) to obtain both NK-EVs and proteins. Precipitated NK-EVs demonstrated potent dose-dependent cytotoxicity against multiple glioblastoma (GBM) cell lines, including those resistant to conventional NK cell therapy. They suppressed tumour growth in subcutaneous GBM xenograft models and, following intravenous administration, significantly inhibited orthotopic brain tumour progression and prolonged survival. SEC-NK-EVs expressed high levels of activating receptors (NKG2D, DNAM-1, NKp30) and effector proteins (perforin, granzyme B) with lower inhibitory receptors (TIGIT, TIM-3, CD96 and LAG3) compared to parental cells. Importantly, both SEC-NK-EVs and proteins exhibited antitumor activity, revealing complementary therapeutic mechanisms within the NK cell secretome. Collectively, these findings establish NK-EVs as an effective cell-free immunotherapy strategy for GBM that has the potential to evade key limitations of adoptive NK cell therapy, including the immunosuppressive tumour microenvironment.
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