Elucidation of the mechanism of immune activation and identification of novel target molecules associated with allogeneic reactions
| Project/Area Number |
16K10541
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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 |
Digestive surgery
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| Research Institution | Kobe University |
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Principal Investigator |
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| Co-Investigator(Kenkyū-buntansha) |
神垣 隆 神戸大学, 医学研究科, 客員教授 (20372641)
岡田 誠治 熊本大学, エイズ学研究センター, 教授 (50282455)
掛地 吉弘 神戸大学, 医学研究科, 教授 (80284488)
藤田 貢 近畿大学, 医学部, 准教授 (40609997)
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| Project Period (FY) |
2016-04-01 – 2019-03-31
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| Project Status |
Completed (Fiscal Year 2018)
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| Budget Amount *help |
¥4,550,000 (Direct Cost: ¥3,500,000、Indirect Cost: ¥1,050,000)
Fiscal Year 2018: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
Fiscal Year 2017: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Fiscal Year 2016: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
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| Keywords | 大腸癌 / 免疫細胞療法 / NKT細胞 / 同種異型反応 / T細胞 / ネオ抗原 / 同種畏系 / メモリーCD8+Ｔ細胞 / 樹状細胞 / ゼノグラフト / メモリーCD8+T細胞 / 同種異系 |
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| Outline of Final Research Achievements |
We aimed to induce the tumor-reactive T cells using allogeneic reactions. To this end, we planned two projects simultaneously. At first, the mechanisms that allogeneic IgG and tumor cells form an immune complex, which is efficiently phagocytosed by dendritic cells in vitro and exerts a strong antigen presenting ability was reported. Using this system, we tried to establish a therapeutic model for colorectal cancer. Currently, we got the results that T cell activation is not sufficient. Second, we advanced induction of tumor-reactive T cells by NKT cell-activating allogeneic vaccine vectors composed of antigen-introduced allogeneic dendritic cells. We succeeded in establishing a vaccine vector using syngeneic dendritic cells. It is suggested that allogeneic dendritic cells show an effect in a lung metastasis model. We established a vaccine vector using allogeneic dendritic cells. It is suggested that allogeneic vaccine vector system showed an effect in a lung metastasis model.
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| Academic Significance and Societal Importance of the Research Achievements |
免疫チェックポイント阻害剤の台頭と共に、奏功症例の解析が進み、がんの発症に伴う遺伝子変異に起因する新生変異抗原(neoantigen)の存在が必要条件であることが示された。変異頻度の高い癌種に neoantigen が出現する傾向があるために、大腸癌に限った場合、Lynch 症候群を中心としたミスマッチ修復機構の欠損を有する症例（MSI-H）に限られる。ただ、neoantigenの同定は煩雑であり、共通性の極めて低いものであり、困難となる。本研究は、neoantigenを同定せずとも免疫療法の機会を失しない、効果的なオーダーメイド治療の確立に貢献するものである。
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Report
(4 results)
Research Products
(16 results)
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[Journal Article] Application of iNKT Cell-targeted Active Immunotherapy in Cancer Treatment.2018
Author(s)
Yamashita K, Arimoto A, Nishi M, Tanaka T, Fujita M, Fukuoka E, Sugita Y, Nakagawa A, Hasegawa H, Suzuki S, Kakeji Y.
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Journal Title
Anticancer Res.
Volume: 38
Pages: 4223-4239
DOI
Related Report
Peer Reviewed / Int'l Joint Research
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[Journal Article] Expression of programmed death-1 in sentinel lymph nodes of breast cancer.2018
Author(s)
Tatara T, Mukohara T, Shimono Y, Yamasaki T, Imamura Y, Funakoshi Y, Toyoda M, Kiyota N, Takao S, Kono S, Kakeji Y, Minami H
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Journal Title
Journal of Surgical Oncology
Volume: Epub ahead of print
Pages: 1131-1136
DOI
Related Report
Peer Reviewed
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