2003 Fiscal Year Final Research Report Summary
Prevention of gastrointestinal tumors by vaccination with clendritic cells transfected with beta-catenine gene.
| Project/Area Number |
13670565
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
Gastroenterology
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| Research Institution | Jikei University School of Medicine |
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Principal Investigator |
HOMMA Sadamu Jikei University School of Medicine, Lecturer, 医学部, 講師 (50192323)
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| Co-Investigator(Kenkyū-buntansha) |
TODA Gotaro Jikei University School of Medicine, Professor, 医学部, 教授 (40090500)
ITO Masaki Jikei University School of Medicine, Research Assistant, 医学部, 助手 (80297366)
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| Project Period (FY) |
2001 – 2003
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| Keywords | Dendritic cell / APC gene mutation / Colorectal cancer / Immunotherapy / Beta-catenine / Gene transfection |
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| Research Abstract |
Development of colorectal cancer is closely associated with mutation of Adenomatous Polyposis Coli (APC) gene mutation, not only in patients with Familiar Adenomatous Polyposis but also in ones with sporadic colorectal cancers. Mutation of APC gene causes Intracellular accumulation of beta-catenine, decomposed promptly by APC gene products in normal cells, which acts as a transcriptional factor in the nucleus, generating malignant transformation of the cell. Abnormal accumulation of beta-catenine in APC gene mutated carcinomatous cells provides a possibility that accumulated beta-catenine might be a target for specifically primed cytotoxic T cells and that beta-catenine-specific antitumor immunity might reject the tumor cells developed on basis of APC gene mutation. We have tried beta-catenine gene transfection into dendritic cells (DCs) and induction of beta-catenine specific antitumor immunity by vaccination with DCs transfected with beta-catenine gene.
First, we tried transfection of genes encoding beta-catenine to DCs by electroporation method using AMAXA system. Transfection of expression vectors caused substantial cell death of DCs. Transfection of mRNA enabled DCs to express the gene products, but the expression was temporal, disappeared within 24 hours, not long enough for vaccination of mice.
We have been trying another method for induction of beta-catenine-specific antitumor immunity. Fibroblasts stably express wild or mutated type beta-catenine were established. DCs and the fibroblasts expressing beta-catenine were fused by treatment with 50% polyethylene glycol. Specific cytotoxic activity to cells that exhibit beta-cate nine accumulation by splenocytes from the mice vaccinated with the DC-fibroblast fusion cells are now being studied. Specific preventive activity for challenge of cancer cells with beta-catenine accumulation (C 26 colon cancer cells) induced by vaccination of mice with the fusion cells will also be examined.
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