Measles Edmonston vaccine strain derivatives have potent oncolytic activity against osteosarcoma

Area of Science:

• Oncology
• Virology
• Biotechnology

Background:

• Osteosarcoma (OS) is the most common primary bone cancer in children and young adults.
• Metastatic disease in OS significantly worsens patient prognosis.
• Novel therapeutic strategies are needed for recurrent and metastatic OS.

Purpose of the Study:

• To evaluate the antitumor efficacy of virotherapy using engineered measles virus (MV) vaccine strains against OS.
• To assess the potential of MV-NIS as a therapeutic agent for OS.
• To explore the use of MV-NIS for in vivo imaging of OS tumors.

Main Methods:

• Infection of pediatric OS cell lines (HOS, MG63, 143B, KHOS-312H, U2-OS, SJSA1) with MV-GFP and MV-NIS.
• Assessment of viral gene expression, syncytial formation, cell death, and monolayer eradication in vitro.
• Evaluation of MV-NIS efficacy in subcutaneous, orthotopic (tibial bone), and lung metastatic OS xenograft models.
• Intratumoral and intravenous administration of MV-NIS.
• In vivo imaging of MV-NIS infected tumors using SPECT and PET-CT.

Main Results:

• Demonstrated viral gene expression and cytotoxicity in OS cell lines.
• Observed significant decrease in subcutaneous OS xenograft tumor growth (P=0.0374).
• Showed prolonged survival in mice with orthotopic (P<0.0001) and pulmonary metastatic OS tumors (P=0.0207).
• Successfully imaged MV-NIS infected tumors in vivo using SPECT and PET-CT.

Conclusions:

• MV-based virotherapy with MV-NIS exhibits significant antitumor efficacy in preclinical OS models.
• MV-NIS demonstrates potential for treating both primary and metastatic osteosarcoma.
• The NIS transgene enables non-invasive imaging of virus-infected tumors, supporting translational applications.