| Project/Area Number |
26430172
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Multi-year Fund |
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| Section | 一般 |
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| Research Field |
Tumor therapeutics
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| Research Institution | Jikei University School of Medicine |
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Principal Investigator |
Masaki Ito 東京慈恵会医科大学, 医学部, 講師 (80297366)
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| Co-Investigator(Kenkyū-buntansha) |
本間 定 東京慈恵会医科大学, 医学部, 教授 (50192323)
小井戸 薫雄 東京慈恵会医科大学, 医学部, 准教授 (70266617)
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| Co-Investigator(Renkei-kenkyūsha) |
SHIBA KIYOTAKA がん研究所, 蛋白創製研究部, 部長 (40196415)
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| Project Period (FY) |
2014-04-01 – 2017-03-31
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| Project Status |
Completed (Fiscal Year 2016)
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| Budget Amount *help |
¥4,940,000 (Direct Cost: ¥3,800,000、Indirect Cost: ¥1,140,000)
Fiscal Year 2016: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
Fiscal Year 2015: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
Fiscal Year 2014: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
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| Keywords | TLR4 / 抗原提示細胞 / 細胞性免疫 / Molcraft / OVA(Ovalbumin) / 人工抗原 / 人工タンパク質 / TLR-4 / MolCraft / OVA (Ovalubumin) / 樹状細胞 / マクロファージ / 人工タンパク質抗原 / OVA / OVA (ovalbumin) |
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| Outline of Final Research Achievements |
From a functional viewpoint, adjuvants are classified into two categories: “physical adjuvants” increase the efficacy of antigen presentation by antigen-presenting cells (APC) and “signal adjuvants” induce the maturation of APC. We created the artificial antigens by appending the TLR4 agonistic peptide motifs to create “adjuvant-free” vaccine. The antigens with TLR4 agonistic motifs have activated NF-κB signaling pathways through TLR4. These proteins also induced the maturation of APC in vitro. Unexpectedly, signal adjuvant-encrypted proteins have lost their ability to be physical adjuvants because they did not induce cytotoxic T lymphocytes in vivo. These results confirmed that the manifestation of a motif’s function is context-dependent and simple addition does not always work for motif-programing. Further optimization of the molecular context of the TLR4 agonistic motifs in antigens should be required to create adjuvant-free antigens.
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