2009 Fiscal Year Final Research Report
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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| Project Period (FY) |
2007 – 2009
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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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