| Project/Area Number |
16K10148
|
|---|
| Research Category |
Grant-in-Aid for Scientific Research (C)
|
| Allocation Type | Multi-year Fund |
|---|
| Section | 一般 |
|---|
| Research Field |
Dermatology
|
|---|
| Research Institution | University of Yamanashi |
|---|
Principal Investigator |
|
|---|
| Research Collaborator |
YAGUCHI tomonori
Togashi Yosuke
|
|---|
| Project Period (FY) |
2016-04-01 – 2019-03-31
|
| Project Status |
Completed (Fiscal Year 2018)
|
| Budget Amount *help |
¥4,680,000 (Direct Cost: ¥3,600,000、Indirect Cost: ¥1,080,000)
Fiscal Year 2018: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Fiscal Year 2017: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Fiscal Year 2016: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
|
|---|
| Keywords | 抗PD-1抗体 / 抗CTLA-4抗体 / TIGIT / LAG3 / メラノーマ / 免疫チェックポイント阻害剤 / PD-1 / LAG-3 / PD-L1 / CD155 / MHC classII / 癌免疫 / 免疫チェックポイント |
|---|
| Outline of Final Research Achievements |
In this study we have shown (1) and (2) as below, in the in vitro experiment using human melanoma tumor infiltrating lymphocytes that are thought to play central role in tumor rejection, and, in the in vivo tumor-treatment model using a humanizes mouse model.
(1) PD-1, TIGIT, and LAG3 are selectively expressed by tumor-infiltrating, tumor-specific T cells, and cooperatively suppress T cell function (2) Co-blockade for their signals by the blocking antibodies synergistically activate the tumor specific T cells.
|
| Academic Significance and Societal Importance of the Research Achievements |
現在、がん治療に使用される抗PD-1抗体、抗CTLA-4抗体は一部のメラノーマ患者に高い効果を示すが、効果がない例、強い副作用が出る例も存在する。本研究では新規免疫チェックポイント候補であるTIGITとLAG3をPD-1とともに阻害すれば効果増強、副作用軽減が可能となる可能性を示した。この結果は今後の免疫チェックポイント阻害剤によるがん治療の効率化、安全化に高く貢献する可能性がある。
|
