2022 Fiscal Year Final Research Report

Establishment of an evaluation model for renal cancer immune niche replication and treatment using next-generation humanized syngeneic mice.

Research Project

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Project/Area Number	20K21652
Research Category	Grant-in-Aid for Challenging Research (Exploratory)
Allocation Type	Multi-year Fund
Review Section	Medium-sized Section 56:Surgery related to the biological and sensory functions and related fields
Research Institution	Kyoto University
Principal Investigator	Ogawa Osamu 京都大学, 医学研究科, 名誉教授 (90260611)
Co-Investigator(Kenkyū-buntansha)	嘉島相輝秋田大学, 医学系研究科, 助教 (50842952) 中村英二郎国立研究開発法人国立がん研究センター, 中央病院, 医長 (90293878) 後藤崇之京都大学, 医学研究科, 講師 (90806605)
Project Period (FY)	2020-07-30 – 2023-03-31
Keywords	免疫チェックポイント阻害剤 / 腎細胞癌 / ヒト化シンジェニックマウス / 患者由来ゼノグラフト / 抗PD-1抗体
Outline of Final Research Achievements	In this study, a humanized mouse model was developed, implanting patient-derived tumor tissue and immune cells, to investigate the effectiveness of immune checkpoint inhibitors (ICIs) in renal cancer treatment. Healthy human peripheral blood mononuclear cells were transplanted into NOG and NOG-DKO immunodeficient mice, establishing three new lines of Patient-Derived Xenografts (PDXs). Upon comparing interactions with human anti-PD-1 antibodies, it was found that the proportion of human CD45+ cells and human CD8+ cells significantly increased in the group treated with human anti-PD-1 antibodies. Additionally, an increase in tumor infiltration was confirmed. Furthermore, combined therapy of anti-PD-1 antibody and a new therapeutic target significantly inhibited the growth of renal cancer. These findings suggest that this novel PDX model can serve as a useful tool in cancer immunology research.
Free Research Field	腎泌尿器腫瘍
Academic Significance and Societal Importance of the Research Achievements	本研究では、同一患者由来の腫瘍組織と免疫細胞を利用した次世代ヒト化シンジェニックマウスモデルを開発に成功した。その結果、免疫チェックポイント阻害剤（ICI）の効果を評価する新しい前臨床モデルが確立された。本研究成果は、ICIの治療効果や耐性・不応性機序をより深く理解し、新たな治療法の開発へとつながる可能性を持つ。さらに、この研究モデルは他の固形癌へも応用が期待され、癌免疫療法研究全体の発展に貢献すると考えられる。