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

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
|October 28, 2020
PubMed
Abstract

Insights

A novel vesicular stomatitis virus (VSV) modified with tumor-suppressor microRNA143 (rVSV-miR143) shows enhanced antitumor effects against osteosarcoma cells in vitro. This modified VSV demonstrates improved cytotoxicity and migration inhibition compared to unmodified VSV.

Area of Science:

  • Oncolytic virotherapy
  • Cancer gene therapy
  • MicroRNA therapeutics

Background:

  • Systemic therapy for osteosarcoma has limitations.
  • Previous studies showed limited long-term survival benefits with vesicular stomatitis virus (VSV) alone.
  • Novel strategies are needed to enhance osteosarcoma treatment.

Purpose of the Study:

  • To develop and evaluate a novel oncolytic VSV engineered to carry tumor-suppressor microRNA143 (rVSV-miR143).
  • To compare the in vitro antitumor efficacy of rVSV-miR143 against osteosarcoma cells with that of unmodified VSV.
  • To determine the optimal dose of rVSV-miR143 for enhanced therapeutic effects.

Main Methods:

  • Engineered a recombinant VSV (rVSV-miR143) incorporating tumor-suppressor microRNA143.
  • Assessed in vitro cytotoxicity and migration inhibition of rVSV-miR143 and VSV on osteosarcoma cells.
  • Compared therapeutic effects across various doses of rVSV-miR143 (10×10-4, 5×10-4, and 1×10-4 multiplicity of infection).

Main Results:

  • rVSV-miR143 exhibited significantly higher cytotoxicity against osteosarcoma cells compared to VSV alone.
  • The migration-inhibitory effects of rVSV-miR143 were also significantly enhanced.
  • Optimal antitumor effects were observed at a dose of 5×10-4 multiplicity of infection.

Conclusions:

  • VSV engineered with tumor-suppressor microRNA143 (rVSV-miR143) demonstrates synergistic antitumor activity against osteosarcoma cells in vitro.
  • rVSV-miR143 represents a promising strategy for enhancing oncolytic virotherapy for osteosarcoma.
  • MicroRNA-mediated enhancement of oncolytic viruses warrants further investigation for cancer treatment.
Keywords:
Vesicular stomatitis virusosteosarcomasystemic therapytumor-suppressor microRNA

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