Development of New Oncolytic Virotherapy Targeting Breast Cancer Using Coxsackievirus B3
Development of New Oncolytic Virotherapy Targeting Breast Cancer Using Coxsackievirus B3
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DOI：
10.21873/anticanres.14753
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发表时间：
2021-01-01
影响因子：
2
通讯作者：
Tani, Kenzaburo
中科院分区：
文献类型：
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作者：
Sagara, Miyako;Miyamoto, Shohei;Tani, Kenzaburo
背景/目的：乳腺癌是世界范围内女性最常见的癌症，三阴性乳腺癌（TNBC）对目前的标准疗法非常难治。溶瘤病毒疗法作为治疗难治性癌症的一种新的候选疗法最近引起了人们的关注。材料与方法：我们以前开发了一种新的柯萨奇病毒B3（CVB 3）病毒治疗靶向肺癌，并证明了miRNA靶序列插入CVB 3降低其致病性，保留其原有的溶瘤活性。在这项研究中，我们研究了CVB 3对乳腺癌细胞（包括TNBC细胞）的溶瘤作用。结果：CVB 3感染能以时间和滴度依赖的方式杀伤乳腺癌细胞，并诱导细胞凋亡。用CVB 3-WT和CVB 3-HP成功地处理了移植有人TNBC细胞的裸鼠。重要的是，用CVB 3-HP治疗的小鼠显示出非常少的不良事件。结论：CVB 3-HP是用于乳腺癌（包括TNBC）的强溶瘤病毒候选物，这是由于其显著的溶瘤功效和改善的安全性特征。
Background/Aim: Breast cancer is the most common cancer in women worldwide, and triple-negative breast cancer (TNBC) is highly refractory to current standard therapies. Oncolytic virotherapy has recently gathered attention as a new treatment candidate for refractory cancers. Materials and Methods: We previously developed a new Coxsackievirus B3 (CVB3) virotherapy targeting lung cancers, and demonstrated that miRNA target sequence insertion into CVB3 reduced its pathogenicity, retaining its original oncolytic activity. In this study, we examined the oncolytic effects of CVB3 against breast cancer cells including TNBC cells. Results: CVB3 infection killed breast cancer cells in a time- and titer-dependent manner, and induced apoptosis. Nude mice transplanted with human TNBC cells were successfully treated with both CVB3-WT and CVB3-HP. Importantly, mice treated with CVB3-HP showed very few adverse events. Conclusion: CVB3-HP is a strong oncolytic virus candidate for breast cancer, including TNBC, due to its remarkable oncolytic efficacy and improved safety profile.