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利用柯萨奇病毒 B3 开发针对乳腺癌的新型溶瘤病毒治疗。

Development of New Oncolytic Virotherapy Targeting Breast Cancer Using Coxsackievirus B3.

机构信息

Laboratory of ALA Advanced Medical Research, Institute for Quantitative Biosciences, The University of Tokyo, Tokyo, Japan.

Laboratory of ALA Advanced Medical Research, Institute for Quantitative Biosciences, The University of Tokyo, Tokyo, Japan

出版信息

Anticancer Res. 2021 Jan;41(1):81-89. doi: 10.21873/anticanres.14753.

Abstract

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.

摘要

背景/目的:乳腺癌是全球女性最常见的癌症,三阴性乳腺癌(TNBC)对当前的标准治疗方法高度耐药。溶瘤病毒治疗最近作为一种难治性癌症的新治疗候选物引起了关注。

材料和方法

我们之前开发了一种针对肺癌的新型柯萨奇病毒 B3(CVB3)溶瘤病毒治疗方法,并证实 miRNA 靶序列插入 CVB3 降低了其致病性,同时保留了其原始的溶瘤活性。在这项研究中,我们研究了 CVB3 对包括 TNBC 细胞在内的乳腺癌细胞的溶瘤作用。

结果

CVB3 感染以时间和滴度依赖的方式杀死乳腺癌细胞,并诱导细胞凋亡。用人类 TNBC 细胞移植的裸鼠成功地接受了 CVB3-WT 和 CVB3-HP 的治疗。重要的是,用 CVB3-HP 治疗的小鼠几乎没有出现不良反应。

结论

由于其显著的溶瘤效果和改善的安全性,CVB3-HP 是一种用于乳腺癌(包括 TNBC)的强力溶瘤病毒候选物。

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