Measles Edmonston vaccine strain derivatives have potent oncolytic activity against osteosarcoma.
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.
1] Medical Oncology, Mayo Clinic, Rochester, MN, USA [2] Department of Molecular Medicine, Mayo Clinic, Rochester, MN, USA.
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Domingo-Musibay
Department of Molecular Medicine, Mayo Clinic, Rochester, MN, USA.
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Allen
Department of Molecular Medicine, Mayo Clinic, Rochester, MN, USA.
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Kurokawa
Department of Molecular Medicine, Mayo Clinic, Rochester, MN, USA.
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Hardcastle
Department of Molecular Medicine, Mayo Clinic, Rochester, MN, USA.
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Aderca
Internal Medicine, Albert Einstein College of Medicine, New York, NY, USA.
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Msaouel
Department of Radiology, Mayo Clinic, Rochester, MN, USA.
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Bansal
Department of Radiology, Mayo Clinic, Rochester, MN, USA.
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Jiang
Department of Radiology, Mayo Clinic, Rochester, MN, USA.
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TR
DeGrado
1] Medical Oncology, Mayo Clinic, Rochester, MN, USA [2] Department of Molecular Medicine, Mayo Clinic, Rochester, MN, USA.
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Galanis
D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D015153:Blotting, Western; D045744:Cell Line, Tumor; D005434:Flow Cytometry; D005818:Genetic Engineering / Q000379:methods*; D015726:Giant Cells / Q000821:virology; D049452:Green Fluorescent Proteins / Q000378:metabolism; D064593:Heterografts / Q000187:drug effects; D006801:Humans; D008175:Lung Neoplasms / Q000188:drug therapy* / Q000556:secondary; D008458:Measles Vaccine / Q000494:pharmacology*; D051379:Mice; D050130:Oncolytic Virotherapy / Q000379:methods*; D012516:Osteosarcoma / Q000188:drug therapy* / Q000473:pathology; D027981:Symporters / Q000235:genetics / Q000378:metabolism / Q000494:pharmacology; D015899:Tomography, Emission-Computed, Single-Photon; D000099209:Sodium-Iodide Symporters
D049452:Green Fluorescent Proteins; D008458:Measles Vaccine; D027981:Symporters; D000099209:Sodium-Iodide Symporters