2020 Fiscal Year Final Research Report

Search of combined cancer immunotherapy with mouse model induced tumor-specific variant antigen

Research Project

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Project/Area Number	18K09291
Research Category	Grant-in-Aid for Scientific Research (C)
Allocation Type	Multi-year Fund
Section	一般
Review Section	Basic Section 56040:Obstetrics and gynecology-related
Research Institution	Shimane University
Principal Investigator	Ishikawa Masako 島根大学, 学術研究院医学・看護学系, 助教 (50467718)
Co-Investigator(Kenkyū-buntansha)	中山健太郎島根大学, 学術研究院医学・看護学系, 准教授 (70346401)
Project Period (FY)	2018-04-01 – 2021-03-31
Keywords	がん免疫療法 / 卵巣がん / マウスモデル
Outline of Final Research Achievements	We investigated effective factor of cancer immunotherapy and the relationship between the effects of cancer immunotherapy and the frequency of somatic mutations and mutation burden in ovarian cancer to find effective treatment groups. The frequency of MSI-High in ovarian cancer was only 4.3%. There was no correlation between MSI status and prognosis and was also no correlation between MSI status and the expression of immune checkpoint-related molecules, so we considered these factors cannot be a predictor for therapeutic effect. We also examined the effects of combination therapy with ICI (immune check point inhibitors) and other anticancer drugs. We prepared mice xenografts which were injected ovarian cancer cell line knocked out POLE, as a model of mutation burden rich. The group of combination therapy could not contribute prognosis improvement. Next, we started to make organoids from ovarian cancer tissue for functional experiments and drug administration experiments.
Free Research Field	婦人科腫瘍
Academic Significance and Societal Importance of the Research Achievements	婦人科癌の中でも死亡率の高い卵巣癌の治療成績向上のため癌免疫療法の効果的な治療群を探索した。癌免疫療法の効果予測因子としてマイクロサテライト不安定性について検討したが、卵巣癌では頻度が少なく、予後との関連も認めなかった。次に、体細胞突然変異の頻度や数が多いPolymerase ε(POLE)変異関連癌のマウスモデルを作製し、抗癌薬と癌免疫療法の併用行ったが、生存期間を延長しなかった。マウスモデルで一定した結果を得られなかったことから、近年、がん微小環境も含めがんの生物学的特性を反映するとされる三次元培養を行い、卵巣癌からオルガノイドモデルを作製し、さらに併用治療実験を進めるところである。