Exploratory Optimization of Organs for Radiotherapy or Cancer Vaccination by Abscopal Effect
| Project/Area Number |
17K10473
|
|---|
| Research Category |
Grant-in-Aid for Scientific Research (C)
|
| Allocation Type | Multi-year Fund |
|---|
| Section | 一般 |
|---|
| Research Field |
Radiation science
|
|---|
| Research Institution | Mie University |
|---|
Principal Investigator |
Watanabe Takashi 三重大学, 医学系研究科, 産学官連携講座教授 (70415529)
|
|---|
| Project Period (FY) |
2017-04-01 – 2021-03-31
|
| Project Status |
Completed (Fiscal Year 2020)
|
| Budget Amount *help |
¥4,680,000 (Direct Cost: ¥3,600,000、Indirect Cost: ¥1,080,000)
Fiscal Year 2019: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
Fiscal Year 2018: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000)
Fiscal Year 2017: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
|
|---|
| Keywords | abscopal effect / 遠隔効果 / 抗PD-1抗体 / 放射線治療 / 定位照射 / 小動物照射装置 / 小動物限局照射装置 / 放射線 / 遮蔽装置 / 組織常在マクロファージ / monocyte / 抗原提示細胞 / 免疫チェックポイント阻害剤 / 複合がん免疫療法 / がん転移巣 / residential macrophage / 細胞傷害性 T 細胞 / 定位放射線療法 / 転移 / 単球 |
|---|
| Outline of Final Research Achievements |
Abscopal effect is tumor reduction effect outside the radiation field. Immune checkpoint inhibitors enhance the effect because PD-L1 is overexpressed in irradiated tumors. The exact mechanism of the effect has not been yet elucidated. The biggest obstacle to disclosure is no local irradiation devices for small animals developed. We first made irradiation devices using lead shield having windows for liver or one lobe of liver. However, all the mice that received a single dose of radiation with various doses were dead. Therefore, we next made a device using a 50 mL-conical tubes covered with lead tunnels, where holes were drilled for stretching one lower limb so that 8 mice could be simultaneously irradiated in the same condition. The device worked well but the “second” melanoma on the upper flank opposite to the lower limb did not show any obvious abscopal effects despite of the optimized schedule of an anti-PD-1 antibody administration starting in advance of radiation initiation.
|
| Academic Significance and Societal Importance of the Research Achievements |
がん末期に症状緩和目的に放射線治療を行うことがあるが、多臓器に亘り転移巣がある場合に、より他の転移巣も縮小させる照射臓器を特定することが期待されたが、明らかにできていない。放射線照射を受けた腫瘍組織においてPD-L1が発現するため、免疫チェックポイント阻害剤抗PD-1抗体を併用すると照射単独よりもabscopal effecが期待でき、至適条件として、照射前から投与することでより効果が得られる。
|
Report
(5 results)
Research Products
(2 results)
