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利用工程化细胞外囊泡提高治疗效果:癌症免疫治疗的进展

Harnessing engineered extracellular vesicles for enhanced therapeutic efficacy: advancements in cancer immunotherapy.

作者信息

Gong Zheng, Cheng Cheng, Sun Chaonan, Cheng Xiaoli

机构信息

Department of Radiology, Shengjing Hospital of China Medical University, Liaoning Province, Shenyang, 110004, China.

Department of Cardiology, Shengjing Hospital of China Medical University, Liaoning Province, Shenyang, 110004, China.

出版信息

J Exp Clin Cancer Res. 2025 May 2;44(1):138. doi: 10.1186/s13046-025-03403-w.

Abstract

Extracellular vesicles (EVs), particularly engineered variants, have emerged as promising tools in cancer immunotherapy due to their inherent ability to modulate immune responses and deliver therapeutic agents with high specificity and minimal toxicity. These nanometer-sized vesicles, which include exosomes (Exos) and other subtypes, naturally participate in intercellular communication and are capable of carrying a diverse range of bioactive molecules, including proteins, lipids, RNAs, and metabolites. Recent advancements in the biogenesis of engineered EVs, such as strategies to modify their surface characteristics and cargo, have significantly expanded their potential as effective vehicles for targeted cancer therapies. Tailoring the contents of EVs, such as incorporating immunomodulatory molecules or gene-editing tools (GETs), has shown promising outcomes in enhancing anti-tumor immunity and overcoming the immunosuppressive tumor microenvironment (TME). Moreover, optimizing delivery mechanisms, through both passive and active targeting strategies, is crucial for improving the clinical efficacy of EV-based therapies. This review provides an overview of recent developments in the engineering of EVs for cancer immunotherapy, focusing on their biogenesis, methods of content customization, and innovations in cargo delivery. Additionally, the review addresses the challenges associated with the clinical translation of EV-based therapies, such as issues related to scalability, safety, and targeted delivery. By offering insights into the current state of the field and identifying key areas for future research, this review aims to advance the application of engineered EVs in cancer treatment.

摘要

细胞外囊泡(EVs),尤其是经过工程改造的变体,由于其具有调节免疫反应以及以高特异性和最小毒性递送治疗剂的内在能力,已成为癌症免疫治疗中有前景的工具。这些纳米级囊泡,包括外泌体(Exos)和其他亚型,自然地参与细胞间通讯,并且能够携带多种生物活性分子,包括蛋白质、脂质、RNA和代谢物。工程化EVs生物发生方面的最新进展,如修饰其表面特征和货物的策略,已显著扩展了它们作为靶向癌症治疗有效载体的潜力。调整EVs的内容物,如纳入免疫调节分子或基因编辑工具(GETs),在增强抗肿瘤免疫力和克服免疫抑制性肿瘤微环境(TME)方面已显示出有前景的结果。此外,通过被动和主动靶向策略优化递送机制,对于提高基于EVs的治疗的临床疗效至关重要。本综述概述了用于癌症免疫治疗的EVs工程的最新进展,重点关注其生物发生、内容物定制方法和货物递送方面的创新。此外,该综述还讨论了与基于EVs的治疗的临床转化相关的挑战,如与可扩展性、安全性和靶向递送相关的问题。通过深入了解该领域的现状并确定未来研究的关键领域,本综述旨在推进工程化EVs在癌症治疗中的应用。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/29ae/12048990/35699fe150cd/13046_2025_3403_Fig1_HTML.jpg

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