Optimization for establishment of Patient derived xenograft model

2019 Fiscal Year Final Research Report

• Project/Area Number: 18K15216
• Research Category: Grant-in-Aid for Early-Career Scientists
• Allocation Type: Multi-year Fund
• Review Section: Basic Section 50010:Tumor biology-related
• Research Institution: Kumamoto University
• Principal Investigator: Kariya Ryusho 熊本大学, ヒトレトロウイルス学共同研究センター, 特任助教 (40757663)
• Project Period (FY): 2018-04-01 – 2020-03-31
• Keywords: 患者腫瘍組織移植モデル / 薬効試験 / 動物モデル / 免疫不全マウス

Outline of Final Research Achievements

Aim of this study is optimization for establishment of PDX model. Firstly we investigated whether pretreatment of tumor tissue before xenograft influence to efficacy of establishment of PDX model or not. There is the possibility that extra cellar matrix (ECM) of tumor tissue inhibit the vascular formation and decrease the efficacy of PDX model establishment. However, physical destruction of ECM by forceps did not influence for efficacy of PDX model establishment. Moreover, we compared the attachment efficacy of patient tumor tissue between NOJ mouse and BRJ mouse. NOJ mouse is more serious immune-deficiency, but BRJ mouse is more resistant for several stress including irradiation and anti-tumor drugs. Interestingly, NOJ mouse and BRJ mouse have no different against efficiency of patient tumor tissue attachment. We also established several PDX derived tumor cell line. These cell line can use for screening of anti-tumor drugs.

Free Research Field

腫瘍免疫学

Academic Significance and Societal Importance of the Research Achievements

抗がん剤の適切な評価を行うためにはヒト患者の病態を忠実に再現したPDXモデルのラインアップであるPDXモデルバンクを樹立する事が極めて重要である。しかしPDXモデルの樹立は未だ高度な技術を有し、樹立効率は決して高くない。本研究はPDXモデルの樹立に影響する要因を検討したという点で非常に学術的、社会的意義を有している。また、本研究で樹立したPDXモデルおよびPDXモデル由来腫瘍細胞株は今後、学会発表や学術論文として世界に発信し、今後の抗がん剤の薬効試験に用いることができるようにする予定である。したがって本研究の結果は新規の抗がん剤の開発に寄与する事となる。