Development of a new strategy to treat cancerous peritonitis

2023 Fiscal Year Final Research Report

• Project/Area Number: 21K19934
• Research Category: Grant-in-Aid for Challenging Research (Exploratory)
• Allocation Type: Multi-year Fund
• Review Section: Medium-sized Section 90:Biomedical engineering and related fields
• Research Institution: Kawasaki Medical School
• Principal Investigator: Nagasaka Takeshi 川崎医科大学, 医学部, 教授 (30452569)
• Co-Investigator(Kenkyū-buntansha): 山口 佳之 川崎医科大学, 医学部, 教授 (10230377) ; 岡脇 誠 川崎医科大学, 医学部, 講師 (40509254) ; 谷岡 洋亮 川崎医科大学, 医学部, 特任研究員 (40775491) ; 矢野 修也 川崎医科大学, 医学部, 講師 (50794624)
• Project Period (FY): 2021-07-09 – 2024-03-31
• Keywords: 難治性癌性腹水 / 脱メチル化剤 / 新規養子免疫細胞療法

Outline of Final Research Achievements

In this study, immune cells and cancer cells obtained from ascites of patients with refractory malignant ascites were co-cultured using the Cell-free and Concentrated Ascites Reinfusion Therapy, followed by the addition of demethylating agents for further culture. As a result, an increase in the viability of immune cells and significant antitumor effects induced by the demethylating agents were observed. Additionally, a technique for detecting the methylation patterns of Differentially Methylated Regions (DMRs) was developed to identify the T cell stage. Consequently, the reversion of immune cells to the effector stage induced by the demethylating agents was confirmed.

Free Research Field

癌治療

Academic Significance and Societal Importance of the Research Achievements

本研究の成果により、難治性癌性腹水から得られる免疫細胞に脱メチル化剤を加えて培養することで、新規養子免疫細胞療法の基礎が得られた。また、免疫細胞がEffector stageに回帰したかを確認するためのDMR methylation pattern検出技術を開発し、脱メチル化剤が免疫細胞にエピジェネティックな変化を誘導し、NaiveからEffector Stageへの誘導、およびExhaustedからEffector Stageへの回帰が起きている可能性を示した。本研究をさらに発展させることで、難治性癌性腹水患者のみならず、すべてのがん患者への新規治療の開発が期待される。