| Project/Area Number |
17016067
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| Research Category |
Grant-in-Aid for Scientific Research on Priority Areas
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| Allocation Type | Single-year Grants |
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| Review Section |
Biological Sciences
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| Research Institution | Jichi Medical University |
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Principal Investigator |
OZAWA Keiya Jichi Medical University, 医学部, 教授 (30137707)
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| Co-Investigator(Kenkyū-buntansha) |
MIZUKAMI Horoaki 自治医科大学, 医学部, 講師 (20311938)
URABE Masashi 自治医科大学, 医学部, 講師 (40213516)
MATSUSHITA Takashi 自治医科大学, 医学部, 助教 (20343444)
OKADA Takashi 自治医科大学, 医学部, 講師 (00326828)
TSUKAHARA Tomonri 自治医科大学, 医学部, 助教 (10362120)
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| Project Period (FY) |
2005 – 2009
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| Project Status |
Completed (Fiscal Year 2009)
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| Budget Amount *help |
¥67,000,000 (Direct Cost: ¥67,000,000)
Fiscal Year 2009: ¥13,400,000 (Direct Cost: ¥13,400,000)
Fiscal Year 2008: ¥13,400,000 (Direct Cost: ¥13,400,000)
Fiscal Year 2007: ¥13,400,000 (Direct Cost: ¥13,400,000)
Fiscal Year 2006: ¥13,400,000 (Direct Cost: ¥13,400,000)
Fiscal Year 2005: ¥13,400,000 (Direct Cost: ¥13,400,000)
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| Keywords | 遺伝子 / ウイルス / 癌 / バイオテクノロジー / 遺伝子治療 / がん遺伝子治療 / AAVベクター / バキュロウイルス / 血管新生 / リンパ管新生 / sFlt-1 / sFlt-4 / VEGF-C / 抗腫瘍血管遺伝子療法 / リンパ行性転移抑制 / 組織特異性 / ヒストン脱アセチル化酵素阻害剤 / 担癌ヌードマウス |
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| Research Abstract |
A) Development of AAV (adeno-associated virus)-mediated cancer gene therapy :
1) Establishment of AAV vector production system using baculovirus expression vectors : AAV vectors were efficiently produced in insect cells. We developed a column chromatographic method to isolate AAV vector particles from empty capsids, which can be adaptable to large-scale production of AAV vectors. Incorporation of the AAV p5 promoter into a transgene sequence increased the efficiency of AAV vector production.
2) Basic studies of the modification of AAV vectors : Chimeric type 5 AAV vectors with type 2 VP1 had a larger amount of VP 1 in their capsids and transduced target cells in a similar manner with parent type 5 AAV vectors.
3) Basic studies of AAV vector-mediated gene transfer and the regulation of transgene expression : We established standard methods of gene transfer into muscle, liver, adipose tissue and peritoneum. A histone deacetylase inhibitor enhanced AAV vector-mediated transgene expression in tumor cells.
4) Examination of strategies for cancer gene therapy using AAV vectors : We conducted gene therapy experiments for refractory cancers (e.g. hematogenous and/or lymphogenous metastasis, and peritoneal dissemination) and showed therapeutic efficacy in tumor-bearing animals.
B) Research on novel strategies for cancer gene therapy : For the treatment of refractory malignant lymphoma (B-cell non-Hodgkin lymphoma), we conducted experiments to develop a novel reinforced adoptive immuno-gene therapy using T-cells expressing a CAR (chimeric antigen receptor) targeting CD 19. We demonstrated that genetically engineered T-cells efficiently lyzed CD 19positive B-cell lymphoma cells in vitro.
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