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免疫病毒治疗中 NK 细胞效应功能与旁观者肿瘤细胞杀伤

英文原题:NK Cell Effector Functions and Bystander Tumor Cell Killing in Immunovirotherapy.

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NK Cell Effector Functions and Bystander Tumor Cell Killing in Immunovirotherapy.

PubMed 2022/01/01(内容时间) Methods Mol Biol

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中文摘要

溶瘤病毒疗法是将癌症基因治疗与免疫疗法结合的一种有吸引力的策略。恶性细胞中的裂解性病毒复制不仅可通过工程化载体实现局部转基因表达,还会诱导免疫原性肿瘤细胞死亡,并在肿瘤微环境中引发炎症。研究者已开发编码免疫调节因子的改造溶瘤病毒,以增强抗肿瘤免疫效应和治疗疗效。例如,可在病毒载体中编码双特异性分子,募集免疫细胞发挥抗肿瘤细胞毒作用。本章节介绍一种体外共培养实验,用于研究编码NK 细胞连接器的工程化麻疹疫苗株病毒的功能和抗肿瘤疗效。基于流式细胞术的分析将检测未感染旁观者癌细胞的死亡以及原代人NK 细胞的效应功能。该方法有助于评估用于癌症免疫治疗的先进溶瘤病毒载体。

展开英文摘要原文

Oncolytic virotherapy is a compelling strategy to combine cancer gene therapy with immunotherapy. Lytic virus replication in malignant cells not only enables localized transgene expression based on engineered vectors but also triggers immunogenic tumor cell death and elicits inflammation in the tumor microenvironment. Modified oncolytic viruses encoding immunomodulators have been developed to enhance antitumor immune effects and therapeutic efficacy. As one example, bispecific molecules that engage immune cells to exert antitumor cytotoxicity can be encoded within the viral vector.

This chapter describes an in vitro coculture experiment to study functionality and antitumor efficacy of engineered measles vaccine strain virus encoding natural killer cell engagers. In a flow cytometry-based analysis, target cell death of noninfected bystander cancer cells and effector functions of primary human natural killer cells are investigated. This methodology can facilitate assessment of advanced oncolytic viral vectors for cancer immunotherapy.

论文信息

作者
Floerchinger A、Engeland CE
第一作者单位
Center for Biomedical Research and Education (ZBAF), School of Medicine, Institute of Virology and Microbiology, Faculty of Health, Witten/Herdecke University, Witten, Germany.Germany
通讯作者单位
Center for Biomedical Research and Education (ZBAF), School of Medicine, Institute of Virology and Microbiology, Faculty of Health, Witten/Herdecke University, Witten, Germany. christine.engeland@uni-wh.de.Germany
期刊
Methods in molecular biology (Clifton, N.J.)2022
原文标识
PubMed 35733001 · DOI 10.1007/978-1-0716-2441-8_12