Antitumor Effect and Immunomodulatory Mechanism of "Oncolytic Extracellular Vesicles".

IF 9.6 1区材料科学 Q1 CHEMISTRY, MULTIDISCIPLINARY

Nano Letters Pub Date : 2024-06-26 DOI:10.1021/acs.nanolett.4c02279

Xinyao Feng, Wenmo Liu, Xinyuan Jia, Fangshen Li, Xupu Wang, Xinyao Liu, Jiahao Yu, Xiaolei Lin, Haihong Zhang, Chu Wang, Hui Wu, Jiaxin Wu, Bin Yu, Xianghui Yu

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Abstract

Enhancing the antitumor immune response and targeting ability of oncolytic viruses will improve the effect of tumor immunotherapy. Through infecting neural stem cells (NSCs) with a capsid dual-modified oncolytic adenovirus (CRAd), we obtained and characterized the "oncolytic extracellular vesicles" (CRAdEV) with improved targeted infection and tumor killing activity compared with CRAd. Both ex vivo and in vivo studies revealed that CRAdEV activated innate immune cells and importantly enhanced the immunomodulatory effect compared to CRAd. We found that CRAdEV effectively increased the number of DCs and activated CD4⁺ and CD8⁺ T cells, significantly increased the number and activation of B cells, and produced higher levels of tumor-specific antibodies, thus eliciting enhanced antitumor activity compared with CRAd in a B16 xenograft immunocompetent mice model. This study provides a novel approach to oncolytic adenovirus modification and demonstrates the potential of "oncolytic extracellular vesicles" in antitumor immunotherapy.

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溶瘤细胞外小泡 "的抗肿瘤作用和免疫调节机制

增强溶瘤病毒的抗肿瘤免疫反应和靶向能力将提高肿瘤免疫治疗的效果。我们通过让神经干细胞（NSCs）感染经过双重修饰的溶瘤腺病毒（CRAd），获得并鉴定了 "溶瘤细胞外囊泡"（CRAdEV），与CRAd相比，CRAdEV具有更强的靶向感染和杀瘤活性。体内外研究均显示，CRAdEV 能激活先天性免疫细胞，与 CRAd 相比，CRAdEV 的免疫调节效果明显增强。我们发现，与 CRAd 相比，CRAdEV 能有效增加 DCs 和活化 CD4+ 和 CD8+ T 细胞的数量，显著增加 B 细胞的数量和活化，并产生更高水平的肿瘤特异性抗体，从而在 B16 异种移植免疫功能正常小鼠模型中激发更强的抗肿瘤活性。这项研究提供了一种新的溶瘤腺病毒修饰方法，证明了 "溶瘤细胞外囊泡 "在抗肿瘤免疫疗法中的潜力。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Nano Letters 工程技术-材料科学：综合

CiteScore

16.80

自引率

2.80%

发文量

1182

审稿时长

1.4 months

期刊介绍： Nano Letters serves as a dynamic platform for promptly disseminating original results in fundamental, applied, and emerging research across all facets of nanoscience and nanotechnology. A pivotal criterion for inclusion within Nano Letters is the convergence of at least two different areas or disciplines, ensuring a rich interdisciplinary scope. The journal is dedicated to fostering exploration in diverse areas, including: - Experimental and theoretical findings on physical, chemical, and biological phenomena at the nanoscale - Synthesis, characterization, and processing of organic, inorganic, polymer, and hybrid nanomaterials through physical, chemical, and biological methodologies - Modeling and simulation of synthetic, assembly, and interaction processes - Realization of integrated nanostructures and nano-engineered devices exhibiting advanced performance - Applications of nanoscale materials in living and environmental systems Nano Letters is committed to advancing and showcasing groundbreaking research that intersects various domains, fostering innovation and collaboration in the ever-evolving field of nanoscience and nanotechnology.