Basic study of immunotherapy for hepatocellular carcinoma by cytotoxic T cell receptor

• Project/Area Number: 25460984
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Gastroenterology
• Research Institution: Kanazawa University
• Principal Investigator: MIZUKOSHI EISHIRO 金沢大学, 医学系, 准教授 (90345611)
• Project Period (FY): 2013-04-01 – 2016-03-31
• Project Status: Completed (Fiscal Year 2015)
• Budget Amount: ¥4,940,000 (Direct Cost: ¥3,800,000、Indirect Cost: ¥1,140,000); Fiscal Year 2015: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000); Fiscal Year 2014: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000); Fiscal Year 2013: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
• Keywords: 癌免疫療法 / Ｔ細胞レセプター / ペプチドワクチン / 肝細胞癌 / ＴＣＲ改変Ｔ細胞 / がん免疫療法 / 遺伝子治療 / アルファフェトプロテイン / ヒトテロメラーゼ逆転写酵素 / 肝細胞がん / ELISPOT / ＥＬＩＳＰＯＴ / Ｃ型肝炎

Outline of Final Research Achievements

In this study, we tried to develop an immunological method to induce a stronger and more efficient cancer immunity using cytotoxic T cell receptor as a cancer immunotherapy for hepatocellular carcinoma patients.
We characterized the cancer antigen-specific cytotoxic T cells induced by peptide vaccine in hepatocellular carcinoma patients. In addition, we could obtain some candidates of cytotoxic T cell receptors useful for immunotherapy of hepatocellular carcinoma and equipped the basic informations to perform clinical studies using the cytotoxic T cell receptors.

Research Products

• [Journal Article] 細胞傷害性T 細胞レセプターを用いた肝細胞癌免疫療法の開発 (2016)
  • Author(s): 水腰 英四郎・中河秀俊・金子 周一
  • Journal Title: BIO Clinica Volume: 31 Pages: 90-96
• [Journal Article] Phase I trial of multidrug resistance-associated protein 3-derived peptide in patients with hepatocellular carcinoma. (2015)
  • Author(s): E Mizukoshi, H Nakagawa, M Kitahara, T Yamashita, K Arai, H Sunagozaka, N Iida, K Fushimi, S Kaneko.
  • Journal Title: Cancer Lett Volume: 369 Issue: 1 Pages: 242-249
  • DOI: 10.1016/j.canlet.2015.08.020
  • NAID: 120005682640
  • Peer Reviewed / Open Access
• [Journal Article] Immunological features of T cells induced by human telomerase reverse transcriptase-derived peptides in patients with hepatocellular carcinoma. (2015)
  • Author(s): E Mizukoshi, H Nakagawa, M Kitahara, T Yamashita, K Arai, H Sunagozaka, K Fushimi, E Kobayashi, H Kishi, A Muraguchi, S Kaneko.
  • Journal Title: Cancer Lett Volume: 364 Issue: 2 Pages: 98-105
  • DOI: 10.1016/j.canlet.2015.04.031
  • Peer Reviewed / Open Access
• [Journal Article] Immunological features of T cells induced by human telomerase reverse transcriptase-derived peptides in patients with hepatocellular carcinoma. (2015)
  • Author(s): Eishiro Mizukoshi, Hidetoshi Nakagawa, Masaaki Kitahara, Tatsuya Yamashita, Kuniaki Arai, Hajime Sunagozaka, Kazumi Fushimi, Eiji Kobayashi, Hiroyuki Kishi, Atsushi Muraguchi, Shuichi Kaneko
  • Journal Title: Cancer Letter Volume: -
  • Peer Reviewed / Acknowledgement Compliant
• [Journal Article] A new cloning and expression system yields and validates TCRs from blood lymphocytes of patients with cancer within 10 days. (2013)
  • Author(s): Kobayashi E., et al
  • Journal Title: Nature Medicne Volume: 19 Issue: 11 Pages: 1542-1546
  • DOI: 10.1038/nm.3358
  • Peer Reviewed
• [Journal Article] Enhancement of tumor-associated antigen-specific T cell responses by radiofrequency ablation of hepatocellular carcinoma (2013)
  • Author(s): 水腰英四郎, 山下竜也
  • Journal Title: Hepatology Volume: 57 Issue: 4 Pages: 1448-1457
  • DOI: 10.1002/hep.26153
  • NAID: 120005254062
  • Peer Reviewed
• [Presentation] Modern Immunologyからみた肝病態 (2015)
  • Author(s): 中河秀俊、水腰英四郎、金子周一
  • Organizer: 第51回日本肝臓病学会総会
  • Place of Presentation: 熊本
  • Year and Date: 2015-05-22
• [Presentation] 肝細胞癌に対する免疫治療の開発 (2015)
  • Author(s): 水腰英四郎、中川秀俊、金子周一
  • Organizer: 第101回日本消化器病学会総会
  • Place of Presentation: 仙台
  • Year and Date: 2015-04-23
• [Presentation] 肝細胞癌に対する免疫治療 (2015)
  • Author(s): 水腰英四郎 金子周一
  • Organizer: 第101回 日本消化器病学会総会
  • Place of Presentation: 仙台国際センター 宮城県
  • Year and Date: 2015-04-23
  • Invited
• [Presentation] Analysis of immune responses in patients vaccinated with alpha-fetoprotein-derived peptides in the treatment of hepatocellular carcinoma. (2014)
  • Author(s): Eishiro Mizukoshi, Tatsuya Yamashita, Kuniaki Arai, Hajime Sunagozaka, Kazumi Fushimi, Hidetoshi Nakagawa, Noriho Iida, Masaaki Kitahara, Shuichi Kaneko
  • Organizer: 第65回 AASLD
  • Place of Presentation: Boston USA
  • Year and Date: 2014-11-10
• [Presentation] 樹状細胞を用いた免疫療法による肝細胞癌ラジオ波焼灼療法後再発の予防 (2014)
  • Author(s): 水腰英四郎 北原征明 金子周一
  • Organizer: 第50回 日本肝臓学会総会
  • Place of Presentation: ホテルニューオータニ 東京都
  • Year and Date: 2014-05-30
• [Presentation] Phase I Trial of Alpha-Fetoprotein-Derived Peptides in the Treatment of Hepatocellular Carcinoma (2013)
  • Author(s): Eishiro Mizukoshi, Tatsuya Yamashita, Kuniaki Arai, Hajime Sunagozaka, Kazumi Fushimi, Hidetoshi Nakagawa, Kazutoshi Yamada, Kiichiro Kaji, Masaaki Kitahara, Shuichi Kaneko
  • Organizer: AASLD The liver meeting 2013
  • Place of Presentation: ワシントンＤＣ アメリカ合衆国 The Walter E. Washington Convention Center
• [Presentation] ヒトテロメラーゼ逆転写酵素由来ペプチドワクチンを用いた肝細胞癌の局所療法後再発抑制の試み (2013)
  • Author(s): 水腰英四郎、山下竜也、金子周一
  • Organizer: 第40回日本肝臓学会西部会
  • Place of Presentation: 岐阜県岐阜市 長良川国際会議場
• [Patent(Industrial Property Rights)] 細胞傷害性Ｔ細胞の作製方法 (2015)
  • Inventor(s): 水腰英四郎 他5名
  • Industrial Property Rights Holder: 金沢大学・富山大学
  • Industrial Property Rights Type: 特許
  • Filing Date: 2015-10-23