Oncolytic Effect of a Recombinant Vesicular Stomatitis Virus Encoding a Tumor-suppressor MicroRNA in an Osteosarcoma

Tomohiko Sakuda1, Tadahiko Kubo2, Muhammad Phetrus Johan3

  • 1Department of Orthopaedic Surgery, Graduate School of Biomedical and Health Sciences, Hiroshima University, Hiroshima, Japan; saakuuda@yahoo.co.jp.

Anticancer Research
|February 28, 2023
PubMed
Abstract

Insights

Vesicular stomatitis virus (VSV) engineered with microRNA143 showed a modest synergistic antitumor effect against osteosarcoma in vivo. Intratumoral delivery significantly reduced primary tumor volume, but did not impact metastasis or survival rates.

Area of Science:

  • Oncolytic virotherapy
  • Gene therapy
  • Cancer research

Background:

  • Vesicular stomatitis virus (VSV) has been explored for osteosarcoma treatment.
  • Previous studies indicated VSV with microRNA143 (VSV-miRNA143) enhanced antitumor effects in vitro, but within a narrow dose range.
  • The in vivo efficacy and synergistic effects of VSV-miRNA143 in osteosarcoma models remained unevaluated.

Purpose of the Study:

  • To evaluate the in vivo oncolytic effect of VSV-miRNA143 on osteosarcoma.
  • To compare the antitumor efficacy of different administration routes (intravenous vs. intratumoral) of VSV-miRNA143 against standard VSV.

Main Methods:

  • A recombinant VSV incorporating tumor-suppressor microRNA143 (rVSV-miR143) was developed.
  • Comparative analysis of primary tumor volume, metastatic lesions, and survival rates in osteosarcoma mouse models.
  • Evaluation of both intratumoral and intravenous administration of rVSV-miR143.

Main Results:

  • Intratumoral administration of rVSV-miR143 led to a significant reduction in primary tumor volume compared to VSV.
  • No significant differences in metastatic lesions or survival rates were observed between rVSV-miR143 and VSV following intratumoral injection.
  • Intravenous administration of rVSV-miR143 showed no significant difference in primary tumor volume, metastatic lesions, or survival rates compared to VSV.

Conclusions:

  • VSV incorporating tumor-suppressor microRNA143 exhibits a mild synergistic antitumor effect in vivo.
  • Intratumoral delivery of rVSV-miR143 shows potential for primary tumor volume reduction in osteosarcoma.
  • Further optimization is needed to enhance the impact on metastasis and survival rates.