Development of novel cancer immunotherapy targeting macrophages using a humanized mouse model

2022 Fiscal Year Final Research Report

• Project/Area Number: 20K16358
• Research Category: Grant-in-Aid for Early-Career Scientists
• Allocation Type: Multi-year Fund
• Review Section: Basic Section 50010:Tumor biology-related
• Research Institution: Osaka University (2021-2022); Kobe University (2020)
• Principal Investigator: Iida Rie 大阪大学, 微生物病研究所, 特任研究員(常勤) (10816771)
• Project Period (FY): 2020-04-01 – 2023-03-31
• Keywords: Bリンパ腫 / 免疫系ヒト化マウス / 腫瘍免疫 / トランスレーショナルリサーチ

Outline of Final Research Achievements

We investigated the antitumor effects of anti-human SIRPα antibody using immunodeficient mice expressing multiple human cytokines that promote homeostatic engraftment of human immune cells and differentiation of human macrophages. Anti-human SIRPα antibody significantly enhanced ADCP of cancer cells by macrophages with anti-CD20 antibody and also inhibited tumor growth in vivo in humanized mice transplanted with human lymphoma cells. These findings suggest that such a humanized mouse model is a suitable new tool for evaluating therapies targeting human macrophages, such as anti-human SIRPα antibodies.

Free Research Field

腫瘍生物学

Academic Significance and Societal Importance of the Research Achievements

In vitroでの薬効評価では複雑な腫瘍免疫環境を再現できず、同系移植などのマウスモデルではヒトに対する抗体医薬が評価できないことから、臨床応用との差異をできるだけなくすためにはヒトの免疫系を有した腫瘍モデルマウスにおいて薬効を評価することが非常に重要である。また免疫系ヒト化マウスを用いた薬効評価系が確立されれば、免疫系を標的とした新規がん治療薬のスクリーニングへの応用も期待される。