| Project/Area Number |
16K08386
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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 |
Medical pharmacy
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| Research Institution | Kobe Pharmaceutical University (2018)
Shujitsu University (2016-2017) |
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Principal Investigator |
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| Co-Investigator(Kenkyū-buntansha) |
井上 大輔 就実大学, 薬学部, 助教 (50550620)
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| Research Collaborator |
Sakane Toshiyasu
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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 |
¥4,810,000 (Direct Cost: ¥3,700,000、Indirect Cost: ¥1,110,000)
Fiscal Year 2018: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
Fiscal Year 2017: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
Fiscal Year 2016: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
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| Keywords | α-galactsylceramide / 鼻腔内投与 / 頸部リンパ節 / 脂肪乳剤 / 樹状細胞 / サイトカイン / 経鼻投与 / 頚部リンパ節 / 免疫賦活 / α-GalCer / 培養細胞層透過 / エマルション / ミセル / 包接化合物 / アルブミン / がん免疫細胞療法 |
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| Outline of Final Research Achievements |
α-Galactosylceramide (GalCer) is a superagonist that activates NKT cells via antigen presenting cells such as dendritic cells and promotes the production of interferon-γ.We investigated the direct delivery of GalCer to CLN of mice, which is the site of activation of NKT cells and the production of cytokines, such as IFN-γ, IL-2, IL-4 and IL12, in serum and CLN after application intranasally of GalCer.
Amount of GalCer in the CLN after application intranasally as emulsion to mice was higher than that as suspension, and the ratio of areas under the time-concentration curve of GalCer in the CLN up to120 min was about 1.5. Furthermore, the amount of cytokines, such as IFN-γ, IL-2, IL-4 and IL12, in serum and CLN also increased by applying intranasally GalCer as emulsion. These results suggested that the intranasal application using emulsions is useful for the efficient delivery of GalCer to the CLN.
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| Academic Significance and Societal Importance of the Research Achievements |
臨床試験中のがん免疫細胞療法は、患者から採取した免疫細胞を体外でα-galactsylceramide（GalCer)と共に培養し、増殖及び活性化した樹状細胞を患者体内に注射により戻す。これを数週間にわたり繰り返すことになるが、患者の身体的・経済的負担は決して軽いものではない。本研究において示された、非侵襲的な鼻腔内投与によるGalCerの頸部リンパ節送達の実現は、患者の苦痛の軽減やQOLの改善につながる。さらに、鼻腔内投与の有用性が上昇することで、がんペプチドワクチン療法やその他注射による治療の代替方法として、患者に寄り添った技術の確立につながっていくと考えている。
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