| Project/Area Number |
18H02699
|
|---|
| Research Category |
Grant-in-Aid for Scientific Research (B)
|
| Allocation Type | Single-year Grants |
|---|
| Section | 一般 |
|---|
| Review Section |
Basic Section 50020:Tumor diagnostics and therapeutics-related
|
|---|
| Research Institution | Kobe Gakuin University |
|---|
Principal Investigator |
|
|---|
| Co-Investigator(Kenkyū-buntansha) |
永田 諭志 国立研究開発法人医薬基盤・健康・栄養研究所, 医薬基盤研究所 創薬デザイン研究センター, プロジェクトリーダー (40246682)
井上 雅己 神戸学院大学, 薬学部, 助教 (80757097)
|
|---|
| Project Period (FY) |
2018-04-01 – 2021-03-31
|
| Project Status |
Completed (Fiscal Year 2020)
|
| Budget Amount *help |
¥17,550,000 (Direct Cost: ¥13,500,000、Indirect Cost: ¥4,050,000)
Fiscal Year 2020: ¥5,070,000 (Direct Cost: ¥3,900,000、Indirect Cost: ¥1,170,000)
Fiscal Year 2019: ¥5,070,000 (Direct Cost: ¥3,900,000、Indirect Cost: ¥1,170,000)
Fiscal Year 2018: ¥7,410,000 (Direct Cost: ¥5,700,000、Indirect Cost: ¥1,710,000)
|
|---|
| Keywords | TNFR2 / APP3 / Treg / MDSC / がん免疫療法 |
|---|
| Outline of Final Research Achievements |
In this project, we investigated the role of TNFR2-APP3 signal in immuno-suppressive function of regulatory T-cells (Treg) and myeloid-derived suppressor cells (MDSC). In addition, we tried to discover an inhibitor of TNFR2-APP3 signal for cancer immunotherapy. TNFR2-APP3 signal is revealed to have important roles in proliferation of Tregs/MDSCs and immuno-suppressive function of Tregs. In addition, TNFR2 was suggested to have a suppressive function in in vivo anti-tumor immunity. These results indicate that TNFR2-APP3 signal is promising as a drug-target for cancer immunotherapy.
|
| Academic Significance and Societal Importance of the Research Achievements |
TNFR2-APP3経路のシグナルの詳細や当該シグナルとTreg/MDSC細胞を介する免疫制御との連関、がん免疫治療における有用性についての詳細は不明であったが、本研究でその一端を解明することができた。昨今、がん免疫療法は大きく期待されているが、これまでTNFR2シグナルの制御をがん免疫療法に応用した例はなく、また、TregやMDSCの機能を抑制できる低分子薬の開発は未踏である。本研究により、TNFR2-APP3シグナル経路を標的とし、がん免疫抑制の中心を担うと考えられるTreg/MDSCの機能の制御に基づくがん免疫療法の可能性が示された。
|
