Oncotarget

Research Papers:

Oncolytic efficacy of thymidine kinase-deleted vaccinia virus strain Guang9

Lili Deng, Jun Fan, Yuedi Ding, Jue Zhang, Bin Zhou, Yi Zhang and Biao Huang _

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Oncotarget. 2017; 8:40533-40543. https://doi.org/10.18632/oncotarget.17125

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Abstract

Lili Deng1, Jun Fan1, Yuedi Ding1, Jue Zhang1, Bin Zhou1, Yi Zhang1 and Biao Huang1

1Key Laboratory of Nuclear Medicine, Ministry of Health, Jiangsu Key Laboratory of Molecular Nuclear Medicine, Jiangsu Institute of Nuclear Medicine, Wuxi, Jiangsu, China

Correspondence to:

Biao Huang, email: huangbiao@jsinm.org

Keywords: vaccinia virus, oncolytic virotherapy, Tian Tan strain Guang9, cancer therapy, thymidine kinase

Received: November 30, 2016     Accepted: April 04, 2017     Published: April 15, 2017

ABSTRACT

Oncolytic virotherapy is being developed as a promising platform for cancer therapy due to its ability to lyse cancer cells in a tumor-specific manner. Vaccinia virus has been used as a live vaccine in the smallpox eradication program and now is being potential in cancer therapy with a great safety profile. Vaccinia strain Guang9 (VG9) is an attenuated Chinese vaccinia virus and its oncolytic efficacy has been evaluated in our previous study. To improve the tumor selectivity and oncolytic efficacy, we here developed a thymidine kinase (TK)-deleted vaccinia virus based on Guang9 strain. The viral replication, marker gene expression and cytotoxicity in various cell lines were evaluated; antitumor effects in vivo were assessed in multiple tumor models. In vitro, the TK-deleted vaccinia virus replicated rapidly, but the cytotoxicity varied in different cell lines. It was notably attenuated in normal cells and resting cells in vitro, while tumor-selectively replicated in vivo. Significant antitumor effects were observed both in murine melanoma tumor model and human hepatoma tumor model. It significantly inhibited the growth of subcutaneously implanted tumors and prolonged the survival of tumor-bearing mice. Collectively, TK-deleted vaccinia strain Guang9 is a promising constructive virus vector for tumor-directed gene therapy and will be a potential therapeutic strategy in cancer treatment.


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