Development of CAR-T immunotherapy targeting molecule X

2018 Fiscal Year Final Research Report

• Project/Area Number: 16H05420
• Research Category: Grant-in-Aid for Scientific Research (B)
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: Digestive surgery
• Research Institution: Showa University (2018); National Cancer Center Japan (2016-2017)
• Principal Investigator: Yoshimura Kiyoshi 昭和大学, 大学共同利用機関等の部局等, 教授 (30346564)
• Co-Investigator(Kenkyū-buntansha): 玉田 耕治 山口大学, 大学院医学系研究科, 教授 (00615841) ; 倉増 敦朗 山口大学, 大学院医学系研究科, 准教授 (90302091)
• Project Period (FY): 2016-04-01 – 2019-03-31
• Keywords: 細胞免疫療法 / 腫瘍免疫療法

Outline of Final Research Achievements

With regard to molecule X, which is a membrane surface protein as a target of CAR-T, the expression of normal tissue was very limited, and high expression was observed in gastrointestinal cancer and pancreatic cancer in cancer tissue. When a cell killing effect targeting this was searched for, a strong effect was observed, but monoclonal antibody production was performed in expectation of a more selective and strong effect.
On the other hand, analysis of the mechanism of anti-tumor effect on activated T cell tumor mass Analysis of the effect of immune cells themselves against solid cancer through experiments and information collection (appropriate activation, invasion ability) The research, which has become a foundation for universal next-generation cell immunotherapy using T cells as well as CAR-T, has been advanced.

Free Research Field

細胞免疫療法、腫瘍免疫療法

Academic Significance and Societal Importance of the Research Achievements

CAR-Tの標的としての膜表面蛋白である分子Xに関して、正常組織の発現はきわめて限定的であり、がん組織で消化管がんと膵がんで高い発現が認められた。これを標的とした殺細胞効果を探索したところ強い効果を認めたが、より選択的で強い効果を期待してモノクローナル抗体作製を行った。
オリジナルな発想の元、メカニズムの解明、CAR-T細胞療法への応用の模索を行っており、早期かつ有効性と安全性に関しても実態のある開発を行いPOCの獲得を目指している。