Development of innovative humanized mouse models for immuno-oncology research of hepatobiliary and pancreatic cancer

2023 Fiscal Year Final Research Report

• Project/Area Number: 20K17044
• Research Category: Grant-in-Aid for Early-Career Scientists
• Allocation Type: Multi-year Fund
• Review Section: Basic Section 53010:Gastroenterology-related
• Research Institution: Kanazawa University
• Principal Investigator: Nio Kouki 金沢大学, 附属病院, 助教 (80807397)
• Project Period (FY): 2020-04-01 – 2024-03-31
• Keywords: 肝胆膵がん / がん免疫療法 / ヒト化マウス / PDXマウスモデル / iPS細胞 / シンジェニックマウスモデル

Outline of Final Research Achievements

Eight PDX models from hepatobiliary and pancreatic cancer tissues were created. From two of these, new pancreatic cancer cell lines were established. A cell line derived from pancreatic cancer cells in ascites was usable not only for subcutaneous tumors but also as a peritoneal dissemination model. From the peripheral blood of two of the eight PDX models, iPS cells were established, and differentiation into CD34-positive hematopoietic stem cells was induced in culture dishes. Although we could not develop a humanized mouse model of the immune system for hepatobiliary and pancreatic cancer through the transplantation of iPS cell-derived hematopoietic stem cells within the study period, we developed a novel syngeneic mouse model of liver cancer that serves as a platform for immuno-oncology research.

Free Research Field

肝胆膵がん

Academic Significance and Societal Importance of the Research Achievements

肝胆膵がんに対する薬物治療効果は未だ十分ではなく、免疫チェックポイント阻害剤などがん免疫療法にかかる期待は大きい。そのため、がん免疫療法の効果を正しく評価できる実験動物モデル開発が必要と考えられている。研究期間内には同一患者を由来とするがん検体と免疫細胞を有するがん免疫系ヒト化モデルの確立は達成し得なかったものの、将来の作製資源となる数種類のPDXモデルの作製ならびに同一患者からのiPS細胞樹立を行った。さらには造血幹細胞分化誘導の知見を得た。また、がん免疫研究のプラットフォームとして新規肝がんシンジェニックマウスモデルを開発した。本モデルは今後のがん免疫研究に有用なモデルとして期待される。