| Project/Area Number |
11671160
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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 |
General surgery
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| Research Institution | KYOTO UNIVERSITY |
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Principal Investigator |
YAMASAKI Seiji Kyoto University, Instructor, 医学研究科, 助手 (50303839)
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| Co-Investigator(Kenkyū-buntansha) |
IMAMURA Masayuki Kyoto University, Professor, 医学研究科, 教授 (00108995)
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| Project Period (FY) |
1999 – 2000
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| Project Status |
Completed (Fiscal Year 2000)
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| Budget Amount *help |
¥3,600,000 (Direct Cost: ¥3,600,000)
Fiscal Year 2000: ¥400,000 (Direct Cost: ¥400,000)
Fiscal Year 1999: ¥3,200,000 (Direct Cost: ¥3,200,000)
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| Keywords | Dendritic cells / messenger RNA / Gene coding for tumor antigen / gene trasduction / Fas ligand / Induction of specific immunity / Th1 / Th2 / T cell receptor repertoire / ヘルパー免疫 / Th_1 / Th_2 / モデル抗原 |
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| Research Abstract |
Using specific cytotoxic T cell lines induced from cocultured with MAGE-3-derived ＆ HLA-A2-binding peptide (FLWGPRALV, amino acids 271-279) -pulsed dendritic cells, we examined the usage of T cell receptor repertoire for recognition of tumor-antigen-derived peptide. We demonstrated the oligoclonal repertoires of TCR Vβ3 and Vβ7 from these CTL lines. For induction of specific immunity with AxCALacZ (as a model tumor antigen) gene-transduced dendritic cells in vivo, we used the helper Th1 immunity (interferon-γ-production and IgG2a production) against β-galactosidase-derived ＆ H-2L^d-binding peptide (TPHPARIGL, amino acids 876-884). Using indicators of these specific immunity against model tumor antigen, we are analysing differences of immune induction with GM-CSF- or interleukin-3-cultured dendritic cells from murine bone marrow. Moreover, we examined tumor-specific immunity by denditic cells cocultured with cationic liposome and tumor-derived messenger RNA (mRNA). Analysing transfection efficiency of dendritic cells with pCAGLacZ and p53 mutation of tumor-derived mRNA, we showed 10% efficiency and increased expression of p53 protein. And in vivo administration of dendritic cells modified by tumor-derived mRNA demonstratted the induction of specific protection immunity and survival prolongation of tumor-bearing mice. For elucidation of in vivo induction of tumor immunity, we are investigating the antigen-uptake and in vivo traffic of dendritic cells after chemotherapy. On the other hand, we are studying the mechanisms of immunosuppression derived from tumor and/or tumor-bearing host including Fas ligand and TRAIL.For clinical applications of tumor-specific vaccine therapy with dendritic cells, we need to investigate tumor immunity in more details.
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