Development of an Experimental Model for Analyzing Immune Checkpoint Inhibitor-Associated Myocarditis

2023 Fiscal Year Final Research Report

• Project/Area Number: 22K15294
• Research Category: Grant-in-Aid for Early-Career Scientists
• Allocation Type: Multi-year Fund
• Review Section: Basic Section 47040:Pharmacology-related
• Research Institution: Okayama University
• Principal Investigator: Hamano Hirofumi 岡山大学, 大学病院, 講師 (10847289)
• Project Period (FY): 2022-04-01 – 2024-03-31
• Keywords: 心筋炎 / 免疫チェックポイント阻害薬 / ドラッグリポジショニング / 実験的発症モデル

Outline of Final Research Achievements

ICI-related myocarditis has a high mortality rate, making the development of preventive and therapeutic drugs urgently necessary. Animal models are essential for the development of new drugs, but the existing model, PD-1-KO-N10, is short-lived and naturally occurring, limiting the period available for analysis and making it difficult to use for new drug development. In contrast, we hypothesize that using a myocarditis inducer on the PD-1-KO-N12 model, which has a lower incidence of myocarditis but longer survival, can create a model that develops myocarditis at an appropriate time while maintaining longevity. In this study, we aim to develop an experimental model of ICI-related myocarditis that is simple and reliable by inducing myocarditis in PD-1-KO-N12 mice.

Free Research Field

医療薬学

Academic Significance and Societal Importance of the Research Achievements

免疫チェックポイント阻害剤（ICIs）による心筋炎は高い致死率を伴うため、その予防及び治療法の開発が急務である。本研究では、効率的な薬剤開発のための新たな動物モデルを開発し、そのモデルを用いてビタミンDの心筋炎予防効果を評価した。
本結果から、ICIs関連心筋炎の予防薬を探索する実験に適していることが示された。ビタミンDが心筋炎の予防に有効であることも示唆され、今後の治療薬開発の有力な候補となり得ることが示唆された。