| Project/Area Number |
17H03571
|
|---|
| Research Category |
Grant-in-Aid for Scientific Research (B)
|
| Allocation Type | Single-year Grants |
|---|
| Section | 一般 |
|---|
| Research Field |
Laboratory animal science
|
|---|
| Research Institution | Tokai University |
|---|
Principal Investigator |
|
|---|
| Co-Investigator(Kenkyū-buntansha) |
真鍋 良幸 大阪大学, 理学研究科, 助教 (00632093)
伊藤 亮治 公益財団法人実験動物中央研究所, 実験動物研究部, 室長代理 (60425436)
徳田 裕 東海大学, 医学部, 客員教授 (20163975)
|
|---|
| Project Period (FY) |
2017-04-01 – 2020-03-31
|
| Project Status |
Completed (Fiscal Year 2019)
|
| Budget Amount *help |
¥18,590,000 (Direct Cost: ¥14,300,000、Indirect Cost: ¥4,290,000)
Fiscal Year 2019: ¥5,330,000 (Direct Cost: ¥4,100,000、Indirect Cost: ¥1,230,000)
Fiscal Year 2018: ¥5,330,000 (Direct Cost: ¥4,100,000、Indirect Cost: ¥1,230,000)
Fiscal Year 2017: ¥7,930,000 (Direct Cost: ¥6,100,000、Indirect Cost: ¥1,830,000)
|
|---|
| Keywords | ヒト化マウス / 妊娠免疫 / ワクチン / 乳がん患者 / 評価技術 |
|---|
| Outline of Final Research Achievements |
We established a tumor-bearing immune environment in human IL-4-producing NOG mouse by transplanting peripheral blood mononuclear cells (PBMC) of healthy donor (HD) and breast cancer (BC) patients. These mice were immunized with HER2 peptide vaccine candidate CH401MAP. We found that in BC mice with the tumor-bearing environment, cytotoxic T cells and specific antibody production after the immunization were significantly reduced. Nivolumab injection decreased PD-1-positive exhausted T cell ratio and increased CD25 positive activated T cell ratio in HD mice, but in BC mice, the Nivolumab did not enhance the activated cytotoxic T cell ratio. Similar phenomena are observed in the mouse transplanted with in HD mice whose PBMC were shortly cultured with glucocorticoid before transplantation but not in the mice with progesterone-treated PBMC.
|
| Academic Significance and Societal Importance of the Research Achievements |
本研究では、妊娠というイベントに伴う他者の受容とTh2への免疫系のシフトの機構を利用してGVHDを抑制する、新たなコンセプトのヒト化マウスを確立した。この系は、個別の患者がん環境を構築したマウスにおける抗がん剤の奏功の評価が可能であるのみならず、妊娠免疫という他者の受容を目的とする特殊な免疫環境を調節するプロゲステロンと、ストレスホルモンであるグルココルチコイドがどのように異なる免疫調節作用を持つかをin vivoにて明らかにした。本研究は特に免疫チェックポイント抗体の腫瘍免疫における役割を明確にするなど、今後の治療法開発の評価系としての可能性を大きく広げたと考えられる。
|
