Chimeric antigen receptor gamma delta T cell immunotherapy for the treatment of malignant mesothelioma

2015 Fiscal Year Final Research Report

• Project/Area Number: 24390326
• Research Category: Grant-in-Aid for Scientific Research (B)
• Allocation Type: Partial Multi-year Fund
• Section: 一般
• Research Field: Thoracic surgery
• Research Institution: The University of Tokyo
• Principal Investigator: Nakajima Jun 東京大学, 医学部附属病院, 教授 (90188954)
• Co-Investigator(Kenkyū-buntansha): KAKIMI Kazuhiro 東京大学, 医学部附属病院, 特任教授 (80273358) ; MURAKAWA Tomohiro 東京大学, 医学部附属病院, 登録研究員 (50359626) ; MATSUSHITA Hirokazu 東京大学, 医学部附属病院, 特任講師 (80597782) ; SANO Atsushi 東京大学, 医学部附属病院, 登録診療員 (20569834)
• Project Period (FY): 2012-04-01 – 2016-03-31
• Keywords: 胸膜中皮腫 / 細胞移入治療 / γδT細胞 / メソテリン / ＣＡＲ / NOGマウス / 細胞傷害活性 / 抗腫瘍効果

Outline of Final Research Achievements

To develop antigen-specific immunotherapy for malignant mesothelioma, we established mesothelin-specific chimeric antigen receptor (MesoCAR) inducedγδTcells. MesoCAR mRNA was transduced into γδTcells, and optimal conditions of MesoCAR+γδTcell adoptive therapy for in vivo and in vitro mesothelioma models were investigated. Anti-tumor effects of MesoCAR+γδTcells were observed, and the anti-tumor effects were comparable to or might be better than those of MesoCAR+ αβTcells. Off-tumor/on-target toxicity to normal tissues was not seen, and the graft-versus host disease was not induced. MesoCAR+ γδTcell adoptive therapy may be an effective treatment without causing major side-effects for mesothelioma or other mesothelin-positive tumors.

Free Research Field

呼吸器外科