Development of Cancer Immunotherapy Utilizing Novel Activation Mechanism of gamma-delta T Cells by 4th Generation Bisphosphonates

2023 Fiscal Year Final Research Report

• Project/Area Number: 18K07274
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Review Section: Basic Section 50020:Tumor diagnostics and therapeutics-related
• Research Institution: Tokyo Women's Medical University
• Principal Investigator: KOBAYASHI Hirohito 東京女子医科大学, 医学部, 准教授 (80318047)
• Project Period (FY): 2018-04-01 – 2024-03-31
• Keywords: 癌性腹膜炎 / ガンマデルタ型T細胞 / 活性化法 / 腎細胞がん / 卵巣がん

Outline of Final Research Achievements

The treatment of refractory ascites due to carcinomatous peritonitis can be alleviated through the use of CART. During the filtration of ascitic fluid in this procedure, gamma delta (γδ) T cells are among the cellular components removed. Research has developed a cell therapy product for cancer immunotherapy by culturing these γδ T cells. When comparing the traditional method using 2M3B-1PP for culturing these cells, the new method employs Tetrakis-pivaloyloxymethyl-2-(thiazole-2-ylamino)ethylidene-1,1-bisphosphonate. This new approach has shown to reduce the contamination of cancer cells and can increase the γδ T cell yield by up to 77 times. Moreover, the cultured γδ T cells maintained their cytotoxic activity even within autologous ascites. The study suggests that intraperitoneal administration of these cultured γδ T cells could be a beneficial therapeutic approach.

Free Research Field

がん免疫療法

Academic Significance and Societal Importance of the Research Achievements

癌性腹膜炎による難治性腹水は、患者のQOLを著しく低下させる。症状緩和に腹水濾過濃縮再静注法が用いられるが、効果は一時的であり複数回の腹腔穿刺が必要である。本研究は本来破棄される細胞成分を用いて癌免疫細胞療法に用いる細胞製剤の開発にある。抗腫瘍活性を有する腹水由来のガンマ・デルタ型T細胞製剤を患者腹腔内へ投与することで難治性腹水の新たな治療戦略となる。また、原料採取に際し新たな患者負担は生じることはなく、持続可能な免疫療法となる。