| Project/Area Number |
13671437
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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 |
Cerebral neurosurgery
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| Research Institution | Yamaguchi University |
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Principal Investigator |
KAJIWARA Koji Yamaguchi University, Hospital, Research Associate, 医学部附属病院, 助手 (90253161)
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| Project Period (FY) |
2001 – 2003
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| Project Status |
Completed (Fiscal Year 2003)
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| Budget Amount *help |
¥3,400,000 (Direct Cost: ¥3,400,000)
Fiscal Year 2003: ¥1,300,000 (Direct Cost: ¥1,300,000)
Fiscal Year 2002: ¥1,000,000 (Direct Cost: ¥1,000,000)
Fiscal Year 2001: ¥1,100,000 (Direct Cost: ¥1,100,000)
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| Keywords | brain tumor / adenoviral vectors / vaccine / B7.1 / IL-4 / 遺伝子治療 |
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| Research Abstract |
In a synoeneic mouse brain tumor model, we tested the hypothesis that vaccination with tumor cells genetically modified to express B7.1 molecules induces tumor-specific T cells and immunological anti-tumor effects
Malignant glioma cells (RSV-MG) derived from a C3H/He mouse induced by Schmidt-Ruppin Rous sarcoma virus wereinfected with an adenovirus encoding the B7.1 gene (AdB7). To investigate the effects of B7.1 expression on the tumorigenicity of RSV-MG cells, infected cells were implanted subcutaneously into C3H/He mice. Furthermore, C3H/He mice were vaccinated with AdB7-transfectants injected subcutaneously and were then challenged intracerebrally two weeks afterward with wild-type RSV-MG cells in order to determine whether or not the expression of B7.1 would enhance the immunogenicity of RSV-MG cells
Immunocytochemistry confirmed die expression of B7.1 and MHC class I antigen on the infected cells. The growth of subcutaneous tumors was markedly retarded in the AdB7 group, whereas tumors had formed and progressively increased in size in the other control groups. In the vaccine experiments, the mice immunized with AdB7-transfectants survived longer than did the mice of the other groups, and a significant difference in survival times vas noted. Immunocytochemistry revealed that brain tumors in mice previously vaccinated with AdB7-infectants had been infiltrated by a larger number of CD3^+ lymphocytes, and that these CD3^+ lymphocytes contained not only CD4^+ and CD8^+ T cells, but also CD25^+-activated T cells. In addition, a cytotoxicity assay confirmed that vaccination with the AdB7-transfectants induced tumor-specific cytotoxicity
These results demonstrate the therapeutic potential of vaccination with tumor cells expressing B7.1 for the treatment of malignant glioma
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