| Project/Area Number |
16591429
|
|---|
| Research Category |
Grant-in-Aid for Scientific Research (C)
|
| Allocation Type | Single-year Grants |
|---|
| Section | 一般 |
|---|
| Research Field |
Cerebral neurosurgery
|
|---|
| Research Institution | Chiba University |
|---|
Principal Investigator |
IWADATE Yasuo Chiba University, Graduate School of Medicine, Assistant, 大学院・医学研究院, 助手 (70272309)
|
|---|
| Co-Investigator(Kenkyū-buntansha) |
TAGAWA Masatoshi Chiba Cancer Center, Research Institute, Director, 研究局, 部長 (20171572)
HIWASA Takaki Chiba University, Graduate School of Medicine, Associate professor, 大学院・医学研究院, 助教授 (30260251)
山浦 晶 千葉大学, 大学院・医学研究院, 教授 (40009717)
|
|---|
| Project Period (FY) |
2004 – 2005
|
| Project Status |
Completed (Fiscal Year 2005)
|
| Budget Amount *help |
¥3,000,000 (Direct Cost: ¥3,000,000)
Fiscal Year 2005: ¥1,200,000 (Direct Cost: ¥1,200,000)
Fiscal Year 2004: ¥1,800,000 (Direct Cost: ¥1,800,000)
|
|---|
| Keywords | small G-proteins / vaccine / immune therapy / gene therapy / glioma |
|---|
| Research Abstract |
Glioblastoma is the most common malignant brain tumor, and it is considered incurable despite multimodal approaches of therapy including surgery, radiotherapy, and chemotherapy. Previously, we have reported that transplantation of the IL-2-producing cells into glioma tissues could recruit sufficient cytotoxic T cells to eliminate established brain tumors in animals immunized with an irradiated whole tumor cell vaccine. By using a proteomic technology, we identified 37 proteins which abundantly expressed in the human glioma tissues. To enhance the vaccination efficiency, we used the small G-proteins (RalA, RhoA, Rac1) among the 37 candidate proteins. We confirmed by quantitative real time RT-PCR that these small G-proteins highly expressed at mRNA level. When these three proteins separated by two dimensional gel electrophoresis were used as subcutaneous vaccine, the treatment efficacies against a rat glioma model did not reach those obtained by inactivated whole tumor cell vaccine. More glioma-specific proteins would be desirable for vaccination against gliomas. To recruit the peripherally-induced cytotoxic T cell into the brain tumors, we constructed a non-transmissible recombinant SeV vector by deleting the matrix (M)- and fusion (F)-genes from its genome, and estimated the therapeutic efficiency of the vector against a rat brain tumor model. The MRI study showed that the intracerebral injection of the vector brought about significant reduction of the tumor growth, including complete elimination of the established brain tumors. The ^<51>Cr release assay confirmed that significant amounts of 9L-specific cytotoxic T cells were induced by the peripheral vaccination. Immunohistochemical analysis revealed that IL-2 was expressed, and CD4^+ T cells and CD8^+ T cells were abundantly infiltrated in the target tumors. During the 3-month follow-up period, no adverse effect was observed.
|
