Development of'BioKnife', a uPA-targeted oncolytic Sendai virus to treat intractable malignancies.
| Project/Area Number |
22659246
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| Research Category |
Grant-in-Aid for Challenging Exploratory Research
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| Allocation Type | Single-year Grants |
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| Research Field |
Digestive surgery
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| Research Institution | Kyushu University |
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Principal Investigator |
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| Co-Investigator(Kenkyū-buntansha) |
YONEMITSU Yoshikazu 九州大学, 薬学研究院, 教授 (40315065)
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| Project Period (FY) |
2010 – 2011
|
| Project Status |
Completed (Fiscal Year 2011)
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| Budget Amount *help |
¥3,230,000 (Direct Cost: ¥2,900,000、Indirect Cost: ¥330,000)
Fiscal Year 2011: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Fiscal Year 2010: ¥1,800,000 (Direct Cost: ¥1,800,000)
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| Keywords | 悪性胸膜中皮腫 / バイオナイフ / センダイウイルス / NF-κB / RIG-Iヘリカーゼ / ウロキナーゼ / 悪性中皮腫 / 消化器がん / 胸膜・腹膜播種 |
|---|
| Research Abstract |
Malignant pleural mesothelioma(MPM) is highly intractable and readily spreads throughout the surface of the pleural cavity, and these cells have been shown to express urokinase-type plasminogen activator receptor(uPAR). We here examined the potential of our new and powerful recombinant Sendai virus(rSeV), which shows uPAR-specific cell-to-cell fusion activity(rSeV/dMFct14(uPA2), named“BioKnife"), for tumor cell killing in two independent orthotopic xenograft models of human. Multicycle treatment using BioKnife resulted in the efficient rescue of these models, in association with tumor-specific fusion and apoptosis. Such an effect was also seen on both MSTO-211H and H226 cells in vitro ; however, we confirmed that the latter expressed uPAR but not uPA. Of interest, infection with BioKnife strongly facilitated the uPA release from H226 cells, and this effect was completely abolished by use of either pyrrolidine dithiocarbamate or BioKnife expressing the C-terminus-deleted dominant negative inhibitor for retinoic acid-inducible gene-I(RIG-IC), indicating that BioKnife-dependent expression of uPA was mediated by the RIG-I/NK-κB axis, detecting RNA viral genome replication. Therefore, these results suggest a proof of concept that the tumor cell-killing mechanism via BioKnife may have significant potential to treat patients with MPM that is characterized by frequent uPAR expression in a clinical setting.
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Report
(3 results)
Research Products
(319 results)
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[Journal Article] Dysregulation of PRMT1 and PRMT6, type I arginine methyltransferases, is involved in various types of human cancers2011
Author(s)
M.Yoshimatsu, G.Toyokawa, S.Hayami, M.Unoki, T.Tsunoda, H.I.Field, J.D.Kelly, D.E.Neal, Y.Maehara, B.A.Ponder, Y.Nakamura, R.Hamamoto
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Journal Title
International Journal of Cancer
Volume: 128
Issue: 3
Pages: 562-573
DOI
Related Report
Peer Reviewed
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[Presentation] 次代の外科学2010
Author(s)
前原喜彦
Organizer
千葉大学大学院先端応用外科学教室例会
Place of Presentation
千葉
Year and Date
2010-12-12
Related Report
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[Presentation] 次代の外科学2010
Author(s)
前原喜彦
Organizer
岡山大学第1外科教室開講記念会
Place of Presentation
岡山
Year and Date
2010-10-03
Related Report
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