| Project/Area Number |
12671337
|
|---|
| Research Category |
Grant-in-Aid for Scientific Research (C)
|
| Allocation Type | Single-year Grants |
|---|
| Section | 一般 |
|---|
| Research Field |
Thoracic surgery
|
|---|
| Research Institution | Chiba Cancer Center Research Institute |
|---|
Principal Investigator |
KOSHIKAWA Nobuko Chiba Cancer Center Research Institute, Division of Pathology, Research Fellow, 病理研究部, 上席研究員 (90260249)
|
|---|
| Co-Investigator(Kenkyū-buntansha) |
FUJISAWA Takehiko Graduate School of Medicine, Chiba University, Thoracic Surgery, Professor, 大学院・医学研究院・胸部外科学, 教授 (80110328)
IIZASA Toshihiko Graduate School of Medicine, Chiba University, Thoracic Surgery, Assistant Professor, 大学院・医学研究院・胸部外科学, 助手 (10272303)
田川 雅敏 千葉県がんセンター, 病理研究部, 部長 (20171572)
|
|---|
| Project Period (FY) |
2000 – 2001
|
| Project Status |
Completed (Fiscal Year 2001)
|
| Budget Amount *help |
¥3,400,000 (Direct Cost: ¥3,400,000)
Fiscal Year 2001: ¥1,400,000 (Direct Cost: ¥1,400,000)
Fiscal Year 2000: ¥2,000,000 (Direct Cost: ¥2,000,000)
|
|---|
| Keywords | gene therapy / CD40 ligand / Fas ligand / TNF-α / lung cancer / lung metastasis / antigen presentaion / dendritic cells / 樹状細胞 |
|---|
| Research Abstract |
Induction of cytotoxic T cells, responsible for cell-mediated immunity, requires the activation of dendritic cells (DC) which play a crucial role in antigen-presentation. We examined in this study whether activation of DC could be performed by gene transfer of the TNF-family gene and consequently antitumor effects were produced against lung cancer cells. Murine lung carcinoma Lewis cells were transfected with the TNF-family gene and established clones were subcutaneously inoculated into syngeneic mice. The growth of CD40 ligand-expressed tumors was significantly retarded compared with that of parent tumors and the number of spontaneous lung metastatic foci was significantly reduced. The immunocompetent mice that were inoculated with the Fas ligand-expressed tumors did not developed tumors and the mice generated tumor-specific protective immunity. The mice did not produce any lung metastatic foci. The growth of the TNF-α-expressed tumors was not different from that of parent tumors but the number of metastatic foci was significantly decreased. In order to analyze the involvement of DC in this antitumor effects, we cocultured DC that were obtained from bone-marrow cells with the transfected cells. DC formed cluster with Fas ligand-expressed but not parent tumors. The expression of CD86, an activation marker an costimulatory molecule of DC, was upregulated during the coculture with CD40 ligand-expressed tumors. Fas ligand and CD40 ligand seem to be involved in antigen processing and maturation of DC, respectively.
|
