Cancer antigen-specific CTL induction and immune cell therapy using cancer antigen peptide, T cell co-stimulation, and immunosuppressive cell regulation

• Project/Area Number: 15K10137
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Digestive surgery
• Research Institution: Shiga University of Medical Science
• Principal Investigator: Miyake Toru 滋賀医科大学, 医学部, 助教 (70581924)
• Co-Investigator(Kenkyū-buntansha): 北村 直美 滋賀医科大学, 医学部, 助教 (30572474) ; 谷 眞至 滋賀医科大学, 医学部, 教授 (60236677) ; 清水 智治 滋賀医科大学, 医学部, 准教授 (70402708) ; 目片 英治 滋賀医科大学, 医学部, 教授 (80314152) ; 村田 聡 滋賀医科大学, 医学部, 講師 (90239525)
• Research Collaborator: Pham Minh Ngoc , 大学院生 ; Kojima MASATSUGU , 助教
• Project Period (FY): 2015-04-01 – 2018-03-31
• Project Status: Completed (Fiscal Year 2017)
• Budget Amount: ¥4,810,000 (Direct Cost: ¥3,700,000、Indirect Cost: ¥1,110,000); Fiscal Year 2017: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000); Fiscal Year 2016: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000); Fiscal Year 2015: ¥2,470,000 (Direct Cost: ¥1,900,000、Indirect Cost: ¥570,000)
• Keywords: 免疫細胞治療 / 養子免疫 / 抗体療法 / 補助刺激 / 免疫チェックポイント阻害 / 腫瘍免疫 / OX40補助刺激 / 細胞治療 / 免疫治療 / 免疫チェックポイント

Outline of Final Research Achievements

The main problems of anti-tumor immune cell therapy are followings; there is a limitation of the number of tumor-specific CTLs that can be induced; CTLs transferred to tumor bearing host cannot proliferate in vivo, lose their function, and undergo apoptosis.
We studied to develop a method by which HER2-specific CTL transferred into the HER2-positive breast tumor-bearing mouse can proliferate in the tumor-bearing environment and maintain antitumor activity. As a result, we have demonstrated that tumor Ag-specific CTLs that were generated in vitro in the presence of an MHC-class I-restricted peptide and OX40 co-stimulation are early-differentiated effector T cells and also have the ability to eradicate tumors, and the potential for expansion and maintenance in tumor-bearing host.

Research Products

• [Journal Article] In vivo antitumor function of tumor antigen-specific CTLs generated in the presence of OX40 co-stimulation in vitro (2018)
  • Author(s): Pham Minh Ngoc、Murata Satoshi、Kitamura Naomi、Ueki Tomoyuki、Kojima Masatsugu、Miyake Toru、Takebayashi Katsushi、Kodama Hirokazu、Mekata Eiji、Tani Masaji
  • Journal Title: International Journal of Cancer Volume: 142 Issue: 11 Pages: 2335-2343
  • DOI: 10.1002/ijc.31244
  • Peer Reviewed
• [Presentation] Immunological activities of adoptively transferred tumor antigen-specific CTLs costimulated with OX40 signaling in vitro (2017)
  • Author(s): Pham Minh Ngoc, Satoshi Murata, Naomi Kitamura, Tomoyuki Ueki, Masatsugu Kojima, Toru Miyake, Katsushi Takebayashi, Hirokazu Kodama, Yuki Kawai, Yataro Daigo, Eiji Mekata, Masaji Tani
  • Organizer: 第76回日本癌学会学術総会
• [Presentation] Using OX40 co-stimulation in vitro to generate tumor antigen-specific CTLs for adoptive cell transfer therapy (2017)
  • Author(s): Pham Minh Ngoc, Satoshi Murata, Naomi Kitamura, Tomoyuki Ueki, Katsushi Takebayashi, Masatsugu Kojima, Toru Miyak, Hirokazu Kodama, Eiji Mekat, Masaji Tani
  • Organizer: 第46回日本免疫学会学術集会