Development of new immuno-cell therapy for the treatment of refractory malignant ascites and pleural effusion

2021 Fiscal Year Final Research Report

• Project/Area Number: 19K09196
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Review Section: Basic Section 55020:Digestive surgery-related
• Research Institution: Shiga University of Medical Science
• Principal Investigator: Kojima Masatsugu 滋賀医科大学, 医学部, 助教 (10452236)
• Co-Investigator(Kenkyū-buntansha): 村田 聡 滋賀医科大学, 医学部, 講師 (90239525) ; 下地 みゆき 滋賀医科大学, 医学部, 技術補佐員 (50796448) ; 目片 英治 滋賀医科大学, 医学部, 教授 (80314152) ; 谷 眞至 滋賀医科大学, 医学部, 教授 (60236677)
• Project Period (FY): 2019-04-01 – 2022-03-31
• Keywords: 胸膜・腹膜転移 / 癌性胸水・腹水 / がん抗原ペプチド / OX40補助刺激 / PD-1阻害薬 / がん抗原特異的CTL

Outline of Final Research Achievements

To establish a cancer antigen-specific CTL that overcomes immune tolerance using immune cells (TAL) in malignant ascites and pleural effusion, immunosuppressive cells were removed from TAL by (1) TGF-β positive cell removal column to prepare the immune environment. In this state, the cells were cultured under (2) cancer antigen peptide stimulation, (3) T cell co-stimulatory factor OX40 stimulation, and immune checkpoint PD-1 inhibition. As a result, HER2-specific CTL could be induced from TAL of HER2-specific immune-tolerant mice, and the antitumor effect on HER2-positive cells was confirmed. A TAL-derived CTL in the malignant ascites of a patient has been established, and the antitumor effect is being evaluated using a PDX mouse peritoneal metastasis model derived from the patient's cancer cells.

Free Research Field

腫瘍免疫

Academic Significance and Societal Importance of the Research Achievements

腹膜転移や胸膜転移による、難治性の癌性腹水・胸水で苦しむ患者は多いが、現医療では効果的な治療はなく、斬新な発想での治療開発研究が必要である。本研究により、免疫環境を整え、効果的に免疫作動薬等を使用すれば、免疫トラレンス環境にある癌性腹水中のリンパ球から、がん抗原特異的CTLが誘導可能なことが示唆された。このCTLは、癌性腹水・胸水へのCTL細胞治療として臨床応用できるだけでなく、その原因である腹膜転移や胸膜転移への治療展開に貢献できるであろう。