Reconstitution of human tumor microenvironment in second generation humanized NOG mice - Development of evaluation systems for cancer immunotherapy

2018 Fiscal Year Final Research Report

• Project/Area Number: 16K18404
• Research Category: Grant-in-Aid for Young Scientists (B)
• Allocation Type: Multi-year Fund
• Research Field: Laboratory animal science
• Research Institution: Central Institute for Experimental Animals
• Principal Investigator: Hanazawa Asami 公益財団法人実験動物中央研究所, 実験動物研究部, 研究員 (40633334)
• Project Period (FY): 2016-04-01 – 2019-03-31
• Keywords: 腫瘍モデル動物 / ヒト化マウス / 次世代NOGマウス / 腫瘍微小環境 / TAM / MDSC

Outline of Final Research Achievements

TAMs (Tumor-associated macrophages) are one of the immunosuppressive myeloid cells which are induced in cancer patients. Although these cells are considered as a key of cancer immune therapy, animal models which allow the evaluation of medicinal effect against these human immunosuppressive cells have not been established. In this study, we induced human TAMs in the animal models based on NOG hIL-6 Tg mice which promote the differentiation of human monocytes and macrophages. Moreover, we indicated that the character and the function of the TAMs in this mice are relating for the cells in cancer patients. In addition, we established the new 2nd generation NOG mice including NOG hM-CSF Tg mice which are usefully for the establishment of human cancer animal models have been established.

Free Research Field

実験動物学

Academic Significance and Societal Importance of the Research Achievements

がん免疫療法は近年目覚ましく発展しているが、その評価に適した実験動物は未だ確立されていない。本研究において樹立されたNOG hIL-6 Tgマウスをはじめとする新規ヒト腫瘍モデル動物は、TAM等のがん患者に特有な細胞を含む様々なヒト免疫細胞を体内に保持し、がん細胞と免疫細胞の相互作用を再現しており、がん免疫療法における新規治療法や新規薬剤の免疫機構への影響を評価することができる。よって、本研究はがん免疫療法の発展に大きく貢献するものである。