Clinical application and development of DNA vaccine gene immunotherapy targeting MUC1 as tumor antigen
| Project/Area Number |
16591392
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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 |
Thoracic surgery
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| Research Institution | Shiga University of Medical Science |
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Principal Investigator |
TAZUKA Noriaki Shiga University of Medical Science, Department of Surgery, Assistant Professor, 医学部, 助手 (40303771)
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| Co-Investigator(Kenkyū-buntansha) |
SAWAI Satoru Shiga University of Medical Science, Department of Surgery, Assistant Professor, 医学部, 助手 (60335172)
FUJINO Shozo Shiga University of Medical Science, Department of Surgery, Associate Professor, 医学部, 助教授 (10209075)
OZAKI Yoshitomo Shiga University of Medical Science, Department of Surgery, Assistant Professor, 医学部, 助手 (00378449)
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| Project Period (FY) |
2004 – 2005
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| Project Status |
Completed (Fiscal Year 2005)
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| Budget Amount *help |
¥3,600,000 (Direct Cost: ¥3,600,000)
Fiscal Year 2005: ¥1,800,000 (Direct Cost: ¥1,800,000)
Fiscal Year 2004: ¥1,800,000 (Direct Cost: ¥1,800,000)
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| Keywords | DNA vaccine / tumor immunotherapy / cytotoxic T cell / helper T cell / MUC1 / 細胞傷害性T細胞 |
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| Research Abstract |
Objective. MUC1 DNA vaccine immunotherapy must induce helper and cytotoxic cell-mediated immunity to generate the powerful anti-tumor immune responses needed to suppress cancer progression. We pay attention to MHC class II peptide (Pan-I a peptide) efficiently stimulated T-helper 1 type lymphocytes which was prepared from the pigeon cytochrome c. We investigated whether co-administration of DNA vaccine and dendritic cells pulsed with Pan-I a peptide (DC-IA) can elicit various immunological mechanism and lead to enhancement of anti-tumor immunity in murine model.
Results. At first instead of MUC1 we used OVA as tumor antigen, C57BL/6 mice were given an injection of DNA encoding OVA (OVA DNA), and we assayed. 1. OVA DNA vaccines could not suppress tumor growth in mice inoculated with E.G7 generated by transducing the chicken OVA gene into EL4 cells. 2. Although the OVA DNA vaccine elicited significant anti-OVA immunity compared with Mock DNA, there was no difference of cytotoxicity against E.G7 between OVA DNA and Mock DNA. 3. Co-administration of OVA DNA and DC-IA elicited tumor specific cytotoxicity, and suppuresive effects on tumor growth in tumor bearing mouse. 4. Tumor infiltrating IFN-γ producing CD4 or CD8 positive cells were significantly increased in mouse bearing E.G7 tumors by vaccination of OVA DNA and DC-IA compared with that in other groups of mice.
Conclusion. Co-administration of DNA vaccine and dendritic cells pulsed with Pan-I a peptide (DC-IA) augemented anti-tumor effects. Now we are investigating this murine model replacing OVA and Pan-I a peptide with MUC1 and Pan-DR peptide (PADRE) that can be presented by various types of mouse and human MHC class II molecules.
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Report
(3 results)
Research Products
(6 results)
