1997 Fiscal Year Final Research Report Summary
Suicide gene therapy and tumor specific CTL activated by B7 gene transfected tumor cells against pancretic cancer.
| Project/Area Number |
08457315
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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 |
Digestive surgery
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| Research Institution | Tohoku University |
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Principal Investigator |
KOBARI Masao Tohoku University, School of Medicine, Lecturer, 医学部, 講師 (30170369)
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| Co-Investigator(Kenkyū-buntansha) |
EGAWA Shin-ichi Tohoku University, Hospital of School of Medicine, Research Associate, 医学部・附属病院, 助手 (00270679)
SUNAMURA Makoto Tohoku University, Hospital of School of Medicine, Research Associate, 医学部・附属病院, 助手 (10201584)
TAKEDA Kazunori Tohoku University, School of Medicine, Lecturer, 医学部, 講師 (20171639)
MATSUNO Seiki Tohoku University, School of Medicine, Professor, 医学部, 教授 (80004737)
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| Project Period (FY) |
1996 – 1997
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| Keywords | pancreatic cancer / gene therapy / suicede gene / immunogene therapy / transfection efficiency / tumor vaccine |
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| Research Abstract |
Pancreatic cancer is one of the most intractable cancer in Japan. In order to achieve a good survival benefit after surgical resection of pancreatic cancer, suicide gene therapy and genetically modified immunotherapy were examined using in vitro and animal experiments. Poorly immunogenic colon26 adenocarcinoma cells were co-transfected with interferon-gamma and B7 adhesion molecule (IFN-gamma/B7/colon26) and utilized as a stimurant to activate cytotoxic T lymphocytes (CTL). The upregulation effect of the endogenous class I molecules and induction of CTL by IFN-gamma/B7 co-transfection appreared to be much stronger than the transfection of B7 alone. The result that intraperitoneal injections with IFN-gamma/B7/colon26 significantly prevented the tumor growth of subcutaneously inoculated wild type colon26 implies the usefulness of co-transfection of B7 and IFN-gamma as a tumor vaccine. On the other hand, in vitro and in vivo transfection efficiency and anti-tumor effects of cytocine deaminase suicide gene driven by CEA promoter was compared using six cationic liposomes, a fusogenic liposome and an adenoviral vector. The latter two vectors were superior to any cationic liposomes in the viewpoint of efficiency and adverse toxicity. No antitumor effects of prodrug 5-FC against peritoneal pancreatic cancer was obtained by in vivo gene transduction mediated by cationic liposome although beta galactosidase was expressed specifically within the disseminated tumors. These data suggests that viral vector and fusogenic liposome might be utilized as an in vivo gene transducer and that more potent pro-drug and modification of by-stander effects are required.
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