Development of an Oncolytic Recombinant Vesicular Stomatitis Virus Encoding a Tumor-suppressor MicroRNA

Background: Attempts have been made to enhance systemic therapy for osteosarcoma. In our previous
study, the systemic administration of a vesicular stomatitis virus (VSV) improved the survival rates of mice with osteosarcoma but did not improve the long-term survival of the animals. Materials and Methods: In the present study, we developed a novel oncolytic VSV by incorporating tumor-
suppressor microRNA143 (rVSV-miR143) to compare the antitumor effects of various doses (10×10–4, 5×10–4, and 1×10–4 multiplicity of infection) of rVSV-miR143 with those of VSV in vitro. Results: The cytotoxicity and migration- inhibitory effects of rVSV-miR143 on the osteosarcoma cells were significantly higher than those of VSV alone at a dose of 5×10–4 multiplicity of infection, indicating that rVSV-miRNA143 enhances the antitumor effect at certain doses. Conclusion: VSV incorporating tumor-suppressor miRNA143 demonstrated a synergistic antitumor effect on osteosarcoma
cells in vitro. The standard treatment for osteosarcoma consists of surgery with adjuvant chemotherapy (1, 2). Especially when it is systemic, this treatment can suppress distant metastasis, improve the survival rate, and reduce the primary tumor, thus enabling the use of surgical procedures that help in conserving the function of the limb (1, 2).