Oncotarget

Research Papers:

Bioluminescence imaging of a tumor-selective, thymidine kinase-defective vaccinia virus Guang9 strain after intratumoral or intraperitoneal administration in mice

Yuedi Ding _, Jun Fan, Lili Deng, Ying Peng, Jue Zhang and Biao Huang

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Oncotarget. 2017; 8:88708-88718. https://doi.org/10.18632/oncotarget.20788

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Abstract

Yuedi Ding1, Jun Fan1, Lili Deng1, Ying Peng1, Jue 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:

Yuedi Ding, email: dingyuedi@jsinm.org

Biao Huang, email: huangbiao@jsinm.org

Keywords: bioluminescence imaging, vaccinia virus, Tian Tan strain Guang9, tumor selectivity

Received: June 22, 2017     Accepted: July 27, 2017     Published: September 08, 2017

ABSTRACT

Vaccinia virus has been used as an oncolytic virus because of its capacity to preferentially infect tumors rather than normal tissues. The vaccinia Tian Tan strain, used as a vaccine against smallpox for millions of people in China, is a promising candidate for cancer therapy. In this study, we constructed an attenuated Tian Tan strain of Guang9 with a disrupted thymidine kinase gene to enhance tumor selectivity and an inserted firefly luciferase to monitor the viral distribution by in vivo bioluminescence imaging. Living animal imaging confirmed the high specificity of vaccinia Guang9 for tumor targeting after intratumoral and intraperitoneal administration. In addition, the vaccinia Guang9 strain produced higher in vivo luciferase activity and endured longer in immunocompromised nude mice than in immunocompetent C57BL/6 mice, all of which had been tumor-challenged. The luciferase activity and viral titers in excised tissues confirmed these conclusions. These data provide evidence for the safety and efficacy of the clinical application of vaccinia virus, which would be a promising approach for cancer therapy.


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