Reovirus FAST Protein Enhances Vesicular Stomatitis Virus Oncolytic Virotherapy in Primary and Metastatic Tumor Models
| Autor: | Roy Duncan, Han He, David W. Hoskin, John C. Bell, Brent Johnston, Nichole McMullen, Simon Gebremeskel, Anna L. Greenshields, Fabrice Le Boeuf, Chungen Pan |
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| Jazyk: | angličtina |
| Rok vydání: | 2017 |
| Předmět: |
0301 basic medicine
Cancer Research Cell type CT26 colon carcinoma viruses Biology lcsh:RC254-282 Green fluorescent protein 03 medical and health sciences 0302 clinical medicine Pharmacology (medical) syncytium formation oncolytic virotherapy Syncytium biology.organism_classification lcsh:Neoplasms. Tumors. Oncology. Including cancer and carcinogens Virology 3. Good health Oncolytic virus 030104 developmental biology Oncology Vesicular stomatitis virus Apoptosis 030220 oncology & carcinogenesis Cancer research Molecular Medicine Immunogenic cell death Original Article 4T1 mammary adenocarcinoma vesicular stomatitis virus FAST protein CD8 |
| Zdroj: | Molecular Therapy Oncolytics Molecular Therapy: Oncolytics, Vol 6, Iss C, Pp 80-89 (2017) |
| ISSN: | 2372-7705 |
| Popis: | The reovirus fusion-associated small transmembrane (FAST) proteins are the smallest known viral fusogens (∼100–150 amino acids) and efficiently induce cell-cell fusion and syncytium formation in multiple cell types. Syncytium formation enhances cell-cell virus transmission and may also induce immunogenic cell death, a form of apoptosis that stimulates immune recognition of tumor cells. These properties suggest that FAST proteins might serve to enhance oncolytic virotherapy. The oncolytic activity of recombinant VSVΔM51 (an interferon-sensitive vesicular stomatitis virus [VSV] mutant) encoding the p14 FAST protein (VSV-p14) was compared with a similar construct encoding GFP (VSV-GFP) in cell culture and syngeneic BALB/c tumor models. Compared with VSV-GFP, VSV-p14 exhibited increased oncolytic activity against MCF-7 and 4T1 breast cancer spheroids in culture and reduced primary 4T1 breast tumor growth in vivo. VSV-p14 prolonged survival in both primary and metastatic 4T1 breast cancer models, and in a CT26 metastatic colon cancer model. As with VSV-GFP, VSV-p14 preferentially replicated in vivo in tumors and was cleared rapidly from other sites. Furthermore, VSV-p14 increased the numbers of activated splenic CD4, CD8, natural killer (NK), and natural killer T (NKT) cells, and increased the number of activated CD4 and CD8 cells in tumors. FAST proteins may therefore provide a multi-pronged approach to improving oncolytic virotherapy via syncytium formation and enhanced immune stimulation. Graphical Abstract |
| Databáze: | OpenAIRE |
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