2007 Fiscal Year Final Research Report Summary
Isolated limb perfusion for vesicular stomatitis virus delivery in sarcoma-bearing rats
| Project/Area Number |
18591633
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
Orthopaedic surgery
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| Research Institution | Hiroshima University |
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Principal Investigator |
KUBO Tadahiko Hiroshima University, Graduate School of Biomedical Sciences, Assistant Professor (70397959)
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| Co-Investigator(Kenkyū-buntansha) |
OCHI Mitsuo Hiroshima University, Hospital, Professor (70177244)
YASUNAGA Yuji Hiroshima University, Graduate School of Biomedical Sciences, Visiting Professor (40253075)
SAKAGUCHI Takemasa Hiroshima University, Graduate School of Biomedical Sciences, Associate Professor (70196070)
SHIMOSE Shouji Hiroshima University, Hospital, Associate Professor (30304439)
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| Project Period (FY) |
2006 – 2007
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| Keywords | Sarcoma / vesicular stomatitis virus / oncolytic virus / Isolated limb perfusion |
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| Research Abstract |
The purpose of this study is to investigate the antitumor effects of vesicular stomatitis virus (VSV) on viability of malignant bone tumor cells and the antitumor effects of VSV administered with isolated limb perfusion in sarcoma-bearing rats. We examined the virus generation (Infection assays), viral replication (Real-time RT-PCR), and antiproliferation effects (Cytotoxicity assays) of VSV in two human osteosarcoma cells (Saos-2, MG-63), a rat osteosarcoma cell (MSK and human normal bone marrow stromal cells (MSC605, 701) Furthermore, we established the isolated limb perfusion system for VSV delivery in sarcoma-bearing immune-competent rats. VSV infected and replicated in osteosarcoma cells selectively and inhibited the viability of all osteosarcoma cell lines in a dose & time-dependent manner. Importantly, VSV affected the viability of normal bone marrow stromal cells much less than sarcoma cells. VSV administered with isolated limb perfusion inhibited the growth of MSK xenograft sarcoma without loss of body weight. Tumor-targeted replicating viruses are being developed as a novel class of oncolytic agents. VSV is nonpathologic RNA virus with inherent specificity for replication in tumor cells due to their attenuated antiviral responses. VSV as an oncolytic virus is particularly appealing for its exceptionally rapid replication rate in tumor cells, such that the oncolytic effects could be maximally manifested before the onset of potentially neutralizing antiviral immune responses in the host. Our findings show that VSV is an effective and safe oncolytic agent against osteosarcoma in immune-competent hosts and warrants further development for future therapy in patients in malignat bone tumors.
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