| Project/Area Number |
15K09224
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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 |
Respiratory organ internal medicine
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| Research Institution | Yokohama City University |
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Principal Investigator |
SATO Takashi 横浜市立大学, 医学部, 講師 (70510436)
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| Co-Investigator(Kenkyū-buntansha) |
下里 剛士 信州大学, 学術研究院農学系, 准教授 (00467200)
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| Research Collaborator |
Klinman Dennis
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| Project Period (FY) |
2015-04-01 – 2018-03-31
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| Project Status |
Completed (Fiscal Year 2017)
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| Budget Amount *help |
¥4,810,000 (Direct Cost: ¥3,700,000、Indirect Cost: ¥1,110,000)
Fiscal Year 2017: ¥1,040,000 (Direct Cost: ¥800,000、Indirect Cost: ¥240,000)
Fiscal Year 2016: ¥910,000 (Direct Cost: ¥700,000、Indirect Cost: ¥210,000)
Fiscal Year 2015: ¥2,860,000 (Direct Cost: ¥2,200,000、Indirect Cost: ¥660,000)
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| Keywords | ナノメディシン / ドラッグデリバリー / 肺癌 / 肺気腫 / 動物モデル / ナノマイクロ粒子 / 免疫治療 / 経気道投与 / 肺癌モデル / ナノ材料 / 癌 / 分子細胞呼吸器学 |
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| Outline of Final Research Achievements |
We have developed inhalable particles-incorporating synthetic oligodeoxynucleotides (ODN) for treating lung diseases. To evaluate the efficacy against lung cancer, we developed a lethal model mimicking primary lung cancer by intratracheal instillation of Lewis lung carcinoma (LLC) cells in C57BL/6 mice, resulting in peribronchial tumor formation with an approximately 22-day median survival. Long-term survivors after treatment with intratracheal administration of particles-incorporating Th1 stimulating ODN were further re-challenged with LLC cells. Although mild-to-moderate alopecia was seen in about 30% of mice that survived for 1 year after previous particle-incorporating ODN treatment, other markers/symptoms of organ damage were not apparent. Histological analysis showed down-regulation of CD3(+)Foxp3(+) and PD-1(+) cells in lung residual tumors in re-challenged mice, leading 100% survival at 1 year by maintaining long-term tumor immunity, and thus preventing cancer recurrence.
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