Establishment of cancer antigen-specific CTL therapy by a concomitant functional regulation of CTL and regulatory T cell and an inhibition of T cell differentiation

• Project/Area Number: 24591973
• 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: MURATA Satoshi 滋賀医科大学, 医学部, 講師 (90239525)
• Co-Investigator(Kenkyū-buntansha): TANI Tohru 滋賀医科大学, 医学部, その他(特任教授) (20179823) ; KURUMI Yoshimasa 滋賀医科大学, 医学部, 教授 (70205219) ; SHIMIZU Tomoharu 滋賀医科大学, 医学部, 助教 (70402708) ; MIYAKE Tohru 滋賀医科大学, 医学部, その他(客員助教) (70581924)
• Project Period (FY): 2012-04-01 – 2015-03-31
• Project Status: Completed (Fiscal Year 2014)
• Budget Amount: ¥5,330,000 (Direct Cost: ¥4,100,000、Indirect Cost: ¥1,230,000); Fiscal Year 2014: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000); Fiscal Year 2013: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000); Fiscal Year 2012: ¥2,080,000 (Direct Cost: ¥1,600,000、Indirect Cost: ¥480,000)
• Keywords: 腫瘍免疫 / 免疫治療 / 癌ワクチン / T細胞補助刺激 / 細胞治療 / 養子免疫 / CTL / OX40 / B7DC / がん免疫治療 / がんワクチン / エフェクター細胞 / 補助刺激 / 癌免疫治療

Outline of Final Research Achievements

We have done the research to develop the efficient cancer-specific CTL therapy, which was to generate CTLs ex vivo and to transfer them into patients.
Cancer-specific CTLs were efficiently generated when T cells were cultured with a cancer antigen and OX40 costimulation that could enhance the effector T cell function. When these cancer-specific CTLs were adoptively transferred into the tumor-bearing mice pretreated with OX40 costimulation that could also inhibit the regulatory T cell function, CTLs could overcome immune tolerance condition, maintain its function, and finally eliminate tumor. IL-2 and/or B7-DC proved to be important molecules that could contribute to the generation of effective CTLs.
Human lymphocytes from the volunteers could generate antigen (HA)-specific CTLs when cultured with an antigen and OX40 stimulation. From these findings, we believe that cancer-specific CTL therapy treated with costimulatory molecules can be applied in a clinical setting in future.

Research Products

• [Journal Article] Surgery-Induced Peritoneal Cancer Cells in Patients Who Have Undergone Curative Gastrectomy for Gastric Cancer. (2014)
  • Author(s): Takebayashi K, Murata S, Yamamoto H, Ishida M, Yamaguchi T, Kojima M, Shimizu T, Shiomi H, Sonoda H, Naka S, Mekata E, Okabe H, Tani T.
  • Journal Title: Ann Surg Oncol Volume: 21 Issue: 6 Pages: 1991-1997
  • DOI: 10.1245/s10434-014-3525-9
  • Peer Reviewed
• [Journal Article] Fusion protein of mutant B7-DC and Fc enhances the antitumor immune effect of GM-CSF-secreting whole-cell vaccine. (2014)
  • Author(s): Kojima M, Murata S, Mekata E, Takebayashi K, Jaffee EM, Tani T.
  • Journal Title: J Immunother Volume: 37(3) Issue: 3 Pages: 147-154
  • DOI: 10.1097/cji.0000000000000025
  • Peer Reviewed
• [Presentation] Curative surgery for gastric cancer induces peritoneal metastasis (2014)
  • Author(s): Satoshi Murata, Katsushi Takebayashi, Hiroshi Yamamoto, Mitsuaki Ishida, Tsuyoshi Yamaguchi, Sachiko Kaida, Tomoharu Shimizu, Hisanori Shiomi, Hiromichi Sonoda, Shigeyuki Naka, Hidetoshi Okabe, Tohru Tani
  • Organizer: 第73回日本癌学会学術総会
  • Place of Presentation: 横浜市
  • Year and Date: 2014-09-25 – 2014-09-27
• [Presentation] The source of cancer cells in peritoneal metastasis after pancreatic surgery for pancreas cancer (2014)
  • Author(s): 村田 聡、竹林克士、塩見尚礼、仲 成幸、赤堀浩也、山本 寛、山口 剛、貝田佐知子、清水智治、園田寛道、太田裕之、目片英治、石田光明、岡部英俊、谷 徹
  • Organizer: 第52回日本癌治療学会
  • Place of Presentation: 横浜市
  • Year and Date: 2014-08-28 – 2014-08-30
• [Presentation] Absorption removal of LAP positive cells from human ascites with cancer treatment column (2014)
  • Author(s): 小島正継、村田聡、寺本和雄、 目片英治、竹林克士、児玉泰一、PhamMinh Ngoc、小笠原一誠、 谷 徹
  • Organizer: 第69回日本消化器外科学会
  • Place of Presentation: 福島県郡山市
  • Year and Date: 2014-07-16 – 2014-07-18
• [Presentation] B7-DC補助刺激を用いた抗腫瘍免疫治療に関する研究 (2013)
  • Author(s): 小島正継 村田 聡 竹林克士 三宅 亨 北村直美 植木智之 目片英治 谷 徹
  • Organizer: 日本癌免疫学会
  • Place of Presentation: 山口県宇部市ANAクラウンプラザホテル
• [Presentation] Fusion Protein of Mutant B7-DC and Fc Enhances the Anti-Tumor Immune Effect of GM-CSF Secreting Whole-Cell Vaccine (2013)
  • Author(s): Masatsugu Kojima, Satoshi Murata, Eiji Mekata, Tohru Miyake, Hiromichi Sonoda and Tohru Tani
  • Organizer: 日本癌学会
  • Place of Presentation: 横浜市パシフィコ横浜