Development of innovative gene therapy of conditionally regulating adenovirus for treating pediatric solid cancer
| Project/Area Number |
19390286
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| Research Category |
Grant-in-Aid for Scientific Research (B)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
Pediatrics
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| Research Institution | Kagoshima University |
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Principal Investigator |
KOSAI Kenichirou Kagoshima University, 大学院・医歯学総合研究所, 教授 (90258418)
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| Co-Investigator(Kenkyū-buntansha) |
小宮 節郎 鹿児島大学, 大学院・医歯学総合研究科, 教授 (30178371)
河野 嘉文 鹿児島大学, 大学院・医歯学総合研究科, 教授 (20260680)
高橋 知之 久留米大学, 医学部, 准教授 (20332687)
前薗 理恵 鹿児島大学, 大学院・医歯学総合研究科, 助教 (90381178)
室伏 善照 鹿児島大学, 大学院・医歯学総合研究科, 助教 (50448578)
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| Project Period (FY) |
2007 – 2009
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| Project Status |
Completed (Fiscal Year 2009)
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| Budget Amount *help |
¥18,330,000 (Direct Cost: ¥14,100,000、Indirect Cost: ¥4,230,000)
Fiscal Year 2009: ¥3,510,000 (Direct Cost: ¥2,700,000、Indirect Cost: ¥810,000)
Fiscal Year 2008: ¥7,020,000 (Direct Cost: ¥5,400,000、Indirect Cost: ¥1,620,000)
Fiscal Year 2007: ¥7,800,000 (Direct Cost: ¥6,000,000、Indirect Cost: ¥1,800,000)
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| Keywords | 遺伝子 / ウイルス / 癌 / トランスレーショナルリサーチ / バイオテクノロジー |
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| Research Abstract |
We previously developed a method to efficiently generate conditionally replicating adenovims that target cancer with multiple-tumor specific factors (m-CRA). Based on this m-CRA technology, we in fact developed survivin-responsive m-CRA (Surv.m-CRA), which selectively replicate in and kill cancer cells (the most of which highly express survivin), as an attractive anticancer agent. Here we modified Surv.m-CRA and developed the improved Surv.m-CRA, which may may increase anticancer effects and tumor-specificity, in order to develop an innovative therapy for treating pediatric solid cancer. The obtained results are the followings.
1. The development of Surv.m-CRA for treating pediatric solid cancer
We replaced the promoter driving mutated E1B with another tumor-specific promoter (osteocalcin) in the original Surv.m-CRA, resulting in a novel type of Surv.m-CRA(OC). Surv.m-CRA(OC) increased tumorp-specificity in ostcosarcoma and prostate cancer without reducing anticancer effect. In this study, we also identified a novel mechanism in viral replication and tumor therapy. The paper was submitted to a scientific journal (under review).
2. Novel m-CRAs that target chromosomal abnormality
We newly developed four m-CRAs that target chromosomal abnormality under the transcriptional regulation using either of four different promoters. We analyzed antitumor effects and clinical utility of the new m-CRAs in animal studies. We obtained the important results that the new m-CRAs had sufficient antitumor effects and tumor-specificity (i.e., safely), suggesting that these m-CRAs may be a innovative anticancer agents. The patent was applied and the paper is being written.
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Report
(4 results)
Research Products
(53 results)
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[Journal Article] Anti-Fas Gene Therapy Prevents Doxorubicin-induced Acute Cardiotoxicity through Mechanisms Independent of Apoptosis2010
Author(s)
Miyata S, Takemura G, Kosai KI, Takahashi T, Esaki M, Li L, Kanamori H, Maruyama R, Goto K, Tsujimoto A, Takeyama T, Kawaguchi T, Ohno T, Nishigaki K, Fujiwara T, Fujiwara H, Minatoguchi S.
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Journal Title
The American Journal of PATHOLOGY 176(2)
Pages: 687-698
Related Report
Peer Reviewed
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[Journal Article] Postinfarction gene therapy with adenoviral vector expressing decorin mitigates cardiac remodeling and dysfunction2009
Author(s)
Li L, Okada H, Takemura G, Kosai KI, Kanamori H, Esaki M, Takahashi T, Goto K, Tsujimoto A, Maruyama R, Kawamura I, Kawaguchi T, Takeyama T, Fujiwara T, Fujiwara H, Minatoguchi S.
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Journal Title
American journal of physiology : Heart and circulatory physiology 294(4)
Related Report
Peer Reviewed
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[Journal Article] Treatment with an adenoviral vector encoding hepatosyte growth factor mitigates established cardiac dysfunction in doxorubicin -induced cardiotnyopathy.2008
Author(s)
Esaki M, Takemura G, Kosai KI, Takahashi T, Miyata S, Li L, Goto K, Maruyama R, Okada H, Kanamori, H, Ogino A, Ushikoshi H, Minatoguchi S, Fujiwara T, Fujiwara H.
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Journal Title
Am J Physiol Heart Circ Physiol. 294(2)
Related Report
Peer Reviewed
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[Journal Article] Treatment with an adenoviral vector encoding hepatosyte growth factor mitigates established cardiac dysfunction in doxorubicin-induced cardiomyopathy.2008
Author(s)
Esaki M, Takemura G, KosaiKI, Takahashi T, Miyata S, Li L, Goto K, Maruyama R, Okada H, Kanamori H, Ogino A, Ushikoshi H, Minatoguchi S, Fujiwara T, Fujiwara H.
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Journal Title
Am J Physiol Heart Circ Physiol. 294(2)
Related Report
Peer Reviewed
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[Journal Article] In vivo hepatocyte growth factor gene transfer reduces myocardial ischemiareperfusion injury through its multiple actions.2007
Author(s)
Chen XH, Minatoguchi S, Kosai K, Yuge K, Takahashi T, Arai M, Wang N, Misao Y, Lu C, Onogi H, Kobayashi H, Yasuda S, Ezaki M, Ushikoshi H, Takemura G, Fujiwara T, Fujiwara H.
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Journal Title
J Card Fail. 13(10)
Pages: 874-883
Related Report
Peer Reviewed
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