文章：

用斑马鱼模拟肿瘤微环境中的溶瘤病毒动力学

Modeling oncolytic virus dynamics in the tumor microenvironment using zebrafish 

原文发布日期：2020-07-10 

英文摘要：

We have adapted a zebrafish (Danio rerio) tumor xenograft model for use in the study of oncolytic virotherapy. Following implantation of mammalian cancer cells into the perivitelline space of developing zebrafish embryos, both local and intravenous oncolytic virus treatments produce a tumor-specific infection with measurable antitumor effects. Tumor cells are injected at 48 h post fertilization, with oncolytic virus treatment then being administered 24 h later to allow for an initial period of tumor development and angiogenesis. Confocal fluorescent imaging is used to quantify dynamics within the tumor environment. The natural translucency of zebrafish at the embryo stage, coupled with the availability of strains with fluorescent immune and endothelial cell reporter lines, gives the model broad potential to allow for real time, in vivo investigation of important events within tumors throughout the course of virotherapy. Zebrafish xenografts offer a system with biologic fidelity to processes in human cancer development that influence oncolytic virus efficacy, and to our knowledge this is the first demonstration of the model’s use in the context of virotherapy. Compared with other models, our protocol offers a powerful, inexpensive approach to evaluating novel oncolytic viruses and oncolytic virus-based combination therapies, with potential application to investigating the impacts of virotherapy on immune response, tumor vasculature, and metastatic disease. 

摘要翻译： 

我们采用斑马鱼（丹尼奥雷里奥）肿瘤异种移植模型用于溶瘤病毒疗法的研究。将哺乳动物癌细胞植入发育期斑马鱼胚胎的卵周间隙后，局部与静脉注射的溶瘤病毒治疗均能产生肿瘤特异性感染，并产生可测量的抗肿瘤效应。肿瘤细胞注射于受精后48小时进行，溶瘤病毒治疗则延迟24小时实施，以便为肿瘤初始发育和血管生成留出时间。通过共聚焦荧光成像技术量化肿瘤微环境内的动态变化。斑马鱼胚胎阶段天然的通透性，结合现有具备荧光标记的免疫细胞和内皮细胞报告品系，使该模型具有实时、活体观察病毒治疗过程中肿瘤内部关键事件的巨大潜力。斑马鱼异种移植系统在生物学上高度模拟人类癌症发展过程中影响溶瘤病毒疗效的进程，据我们所知，这是该模型在病毒治疗领域的首次应用验证。相较于其他模型，我们的方案为评估新型溶瘤病毒及基于溶瘤病毒的联合疗法提供了高效且经济的研究途径，并具备应用于研究病毒治疗对免疫应答、肿瘤血管系统及转移性病变影响的潜力。

原文链接：

Modeling oncolytic virus dynamics in the tumor microenvironment using zebrafish