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Measles Edmonston vaccine strain derivatives have potent oncolytic activity against osteosarcoma

Cancer Gene Therapy volume 21, pages 483–490 (2014)Cite this article

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Abstract

Osteosarcoma (OS) is the most common primary bone tumor affecting children and young adults, and development of metastatic disease is associated with poor prognosis. The purpose of this study was to evaluate the antitumor efficacy of virotherapy with engineered measles virus (MV) vaccine strains in the treatment of OS. Cell lines derived from pediatric patients with OS (HOS, MG63, 143B, KHOS-312H, U2-OS and SJSA1) were infected with MV expressing green fluorescent protein (MV-GFP) and MV-expressing sodium iodide symporter (MV-NIS) strains. Viral gene expression and cytotoxicity as defined by syncytial formation, cell death and eradication of cell monolayers were demonstrated. Findings were correlated with in vivo efficacy in subcutaneous, orthotopic (tibial bone) and lung metastatic OS xenografts treated with the MV derivative MV-NIS via the intratumoral or intravenous route. Following treatment, we observed decrease in tumor growth of subcutaneous xenografts (P=0.0374) and prolongation of survival in mice with orthotopic (P<0.0001) and pulmonary metastatic OS tumors (P=0.0207). Expression of the NIS transgene in MV-NIS infected tumors allowed for single photon emission computed tomography and positron emission tomography–computed tomography imaging of virus infected tumors in vivo. Our data support the translational potential of MV-based virotherapy approaches in the treatment of recurrent and metastatic OS.

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Acknowledgements

We thank Ianko Iankov, MD, PhD for his methodological assistance and kindly providing the anti MV nucleoprotein antibody used in this study. We also thank Mark Federspiel, PhD and the Viral Vector Production Laboratory (Mayo Clinic) for providing MV-NIS preparations used in our studies and Hirosha Geekiyanage, PhD for technical advice and helpful discussions. Support for this research provided by the Clinical Investigator Training Program and a small grant from the Department of Oncology, Mayo Clinic; and NCI/NIH grants R01CA 154348 and R01CA 136547.

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Authors and Affiliations

  1. Medical Oncology, Mayo Clinic, Rochester, MN, USA

    E Domingo-Musibay & E Galanis

  2. Department of Molecular Medicine, Mayo Clinic, Rochester, MN, USA

    E Domingo-Musibay, C Allen, C Kurokawa, J J Hardcastle, I Aderca & E Galanis

  3. Internal Medicine, Albert Einstein College of Medicine, New York, NY, USA

    P Msaouel

  4. Department of Radiology, Mayo Clinic, Rochester, MN, USA

    A Bansal, H Jiang & T R DeGrado

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  1. E Domingo-Musibay
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Domingo-Musibay, E., Allen, C., Kurokawa, C. et al. Measles Edmonston vaccine strain derivatives have potent oncolytic activity against osteosarcoma. Cancer Gene Ther 21, 483–490 (2014). https://doi.org/10.1038/cgt.2014.54

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