Oncolytic vesicular stomatitis virus administered by isolated limb perfusion suppresses osteosarcoma growth

Area of Science:

• Oncolytic virotherapy
• Viral oncology
• Cancer gene therapy

Background:

• Oncolytic virotherapy faces challenges in effective in vivo virus delivery.
• Vesicular stomatitis virus (VSV) demonstrates oncolytic potential against cancer cells.
• Osteosarcoma is a challenging bone cancer with limited treatment options.

Purpose of the Study:

• To evaluate the oncolytic activity of VSV against human osteosarcoma cells.
• To explore isolated limb perfusion (ILP) as a novel delivery system for VSV in extremity sarcoma.
• To assess the efficacy and safety of ILP-delivered VSV in an in vivo model.

Main Methods:

• In vitro assessment of VSV replication and cytolytic activity in human and rat osteosarcoma cell lines.
• Intra-arterial delivery of VSV via ILP to hind limb osteosarcoma xenografts in immune-competent rats.
• Comparison of ILP delivery with intravenous and intratumoral VSV administration.
• Histopathological analysis for VSV-G protein expression in tumors and various organs.

Main Results:

• VSV efficiently replicated in and killed osteosarcoma cells, sparing normal bone marrow stromal cells.
• ILP delivery of VSV resulted in potent inhibition of osteosarcoma xenograft growth compared to other methods.
• VSV-G protein was detected in tumor lesions but not in perfused or non-perfused muscles or major organs, indicating localized activity.
• No significant VSV-G expression was observed in healthy tissues, suggesting a favorable safety profile.

Conclusions:

• Osteosarcoma is a viable target for VSV-based oncolytic virotherapy.
• ILP represents a novel and effective delivery strategy for oncolytic viruses in treating extremity sarcomas.
• VSV delivered via ILP demonstrates significant antitumor activity with localized expression, warranting further clinical investigation.