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.
Highlights
Despite advances in conventional therapies, we lack knowledge and effective treatments for many cancers [1]
We performed a plaque assay to determine the titer of the purified vaccinia virus Guang9 strain (VG9)-Luc, and characterized the luciferase expression in a 6-well plate by luminescence imaging
The luminescence imaging showed increasing luciferase activity in the cells infected with increasing titers of vaccinia VG9 strain carrying Luc (VG9-Luc) (Figure 1b and 1d)
Summary
Despite advances in conventional therapies, we lack knowledge and effective treatments for many cancers [1]. The major treatment options for cancers, including surgery, radiation therapy, and chemotherapy, have been combined to improve outcomes for solid tumors [2, 3]. New cancer therapies with complementary mechanisms of action are needed. Cancer therapy using oncolytic viruses represents a promising new approach for controlling tumors. The therapy is based on the capacity of oncolytic viruses to target and lyse tumor cells to induce antitumor effects [5]. Vaccinia virus possesses a large linear double-stranded DNA genome consisting of approximately 250 genes, with the capacity for the insertion of therapeutic transgenes, such as the human granulocyte-macrophage colony-stimulating factor (hGMCSF) gene [12,13,14]
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