Development of immunotherapy for hepatocellular carcinoma by peptide vaccine

• Project/Area Number: 22590723
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: Gastroenterology
• Research Institution: Kanazawa University
• Principal Investigator: MIZUKOSHI Eishiro 金沢大学, 大学病院, 講師 (90345611)
• Project Period (FY): 2010 – 2012
• Project Status: Completed (Fiscal Year 2012)
• Budget Amount: ¥4,420,000 (Direct Cost: ¥3,400,000、Indirect Cost: ¥1,020,000); Fiscal Year 2012: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000); Fiscal Year 2011: ¥1,040,000 (Direct Cost: ¥800,000、Indirect Cost: ¥240,000); Fiscal Year 2010: ¥2,210,000 (Direct Cost: ¥1,700,000、Indirect Cost: ¥510,000)
• Keywords: ELISPOTアッセイ / ヘルパーT細胞 / ペプチド / ワクチン / 免疫治療 / 肝細胞癌 / CTL / AFP / 肝細胞がん / hTERT / エピトープ

Research Abstract

In the present study, we tried to develop immunotherapy for hepatocellular carcinoma (HCC) by peptide vaccine. The following results were obtained from this study. 1) The helper T cell (HTL) epitopes in AFP and hTERT were identified. 2) Immune responses against these HTL epitopes in peripheral blood mononuclear cells of HCC patients were observed. 3) Peptide vaccines encoding amino acid sequences in the HTL epitopes were developed based on the above results.

Research Products

• [Journal Article] Discrete nature of EpCAM(+) and CD90(+) cancer stem cells in human hepatocellular carcinoma. (2013)
  • Author(s): Yamashita T, Nakamoto Y, et al.
  • Journal Title: Hepatology Volume: 57 Issue: 4 Pages: 1484-1497
  • DOI: 10.1002/hep.26168
  • 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
• [Journal Article] Expression of Chondroitin-glucuronate C5-epimerase and Cellular Immune Responses in Patients with Hepatocellular Carcinoma (2012)
  • Author(s): 水腰英四郎, 伏見一美
  • Journal Title: Liver International Volume: 32 Issue: 10 Pages: 1516-1526
  • DOI: 10.1111/j.1478-3231.2012.02853.x
  • NAID: 120004997021
  • Peer Reviewed
• [Journal Article] Identification of Aldo-Keto Reductase 1C3-derived Peptides Recognized by Cytotoxic T Cells in Hepatocellular Carcinoma Patients. (2012)
  • Author(s): 水腰英四郎, 本多政夫
  • Journal Title: Immuno-Gastroenterology Volume: 1 Issue: 1 Pages: 47-57
  • DOI: 10.7178/ig.1.1.10
  • Peer Reviewed
• [Journal Article] Prospects of Immunotherapy for Hepatocellular Carcinoma (2012)
  • Author(s): 水腰英四郎, 金子周一
  • Journal Title: Immuno-Gastroenterology Volume: 1 Issue: 2 Pages: 47-57
  • DOI: 10.7178/ig.12
• [Journal Article] Identification of Aldo-Keto Reductase 1C3-Derived Peptides Recognized by Cytotoxic T Cells in Hepatocellular Carcinoma Patients (2012)
  • Author(s): Mizukoshi E
  • Journal Title: Immuno-Gastroenterology Volume: (in press)
  • Peer Reviewed
• [Journal Article] Comparative analysis of various tumor-associated antigen-specific t-cell responses in patients with hepatocellular carcinoma (2011)
  • Author(s): Honda M, (他9名, 9番目)
  • Journal Title: Hepatology Volume: 53(4) Issue: 4 Pages: 206-16
  • DOI: 10.1002/hep.24149
  • Peer Reviewed
• [Journal Article] Frequency of CD45R0(+) subset in CD4(+)CD25(high) regulatory T cells a ssociated with progression of hepatocellular carcinoma (2011)
  • Author(s): Takata y
  • Journal Title: Cancer Lett Volume: 307 Pages: 165-173
  • Peer Reviewed
• [Presentation] A phase I study of vaccination with human telomerase reversetranscriptase-derived peptide in patients with hepatocellular carcinoma (2012)
  • Author(s): 水腰英四郎
  • Organizer: The 63rd annual meeting of the American association for the study of liver disease
  • Place of Presentation: Hynes Convention Center(USA)
  • Year and Date: 2012-11-10
• [Presentation] 肝細胞がんに対する免疫療法の開発 (2012)
  • Author(s): 水腰英四郎
  • Organizer: 第16回日本がん免疫学会総会
  • Place of Presentation: 北海道大学学術交流会館(北海道)
  • Year and Date: 2012-07-28
• [Presentation] 肝細胞癌に対するラジオ波焼灼療法による腫瘍関連抗原特異的T細胞の増強 (2012)
  • Author(s): 水腰英四郎
  • Organizer: 第48回日本肝臓学会
  • Place of Presentation: 第48回日本肝臓学会
  • Year and Date: 2012-06-08
• [Presentation] ペプチドワクチンによる肝細胞癌免疫療法の開発 (2012)
  • Author(s): 水腰英四郎
  • Organizer: 第98回日本消化器病学会総会
  • Place of Presentation: 京王プラザホテル(東京都)
  • Year and Date: 2012-04-19
• [Presentation] A phase I study of vaccination with human telomerase reverse transcriptase-derived peptide in patients with hepatocellular carcinoma. (2012)
  • Author(s): 水腰英四郎
  • Organizer: The 63rd annual meeting of the American association for the study of liver disease
  • Place of Presentation: Hynes Convention Center(USA)
• [Presentation] 肝細胞癌に対するラジオ波焼灼療法による腫瘍関連抗原特異的T細胞の増強 (2012)
  • Author(s): 水腰英四郎
  • Organizer: 第48回日本肝臓学会総会
  • Place of Presentation: ANAクラウンプラザホテル（石川県）
• [Presentation] ペプチドワクチンによる肝細胞癌免疫療法の開発 (2012)
  • Author(s): 水腰英四郎
  • Organizer: 第98回日本消化器病学会総会
  • Place of Presentation: 京王プラザホテル（東京都）
• [Presentation] 肝細胞がんに対する免疫療法の開発 (2012)
  • Author(s): 水腰英四郎
  • Organizer: 第16回日本がん免疫学会総会
  • Place of Presentation: 北海道大学学術交流会館（北海道）
• [Presentation] Enhancement of tumorassociated antigen-specific T cellresponses by radiofrequency ablation of hepatocellular carcinoma (2011)
  • Author(s): 水腰英四郎
  • Organizer: The 62nd annual meeting of the American association for the study of liver disease
  • Place of Presentation: Moscone West (USG)
  • Year and Date: 2011-11-08
• [Presentation] Enhancement of tumor-associated antigen-specific T cell responses by radiofrequency ablation of hepatocellular carcinoma (2011)
  • Author(s): 水腰英四郎
  • Organizer: 第62回アメリカ肝臓病学会
  • Place of Presentation: Moscone West Convention Center(サンフランシスコ)
  • Year and Date: 2011-11-08
• [Presentation] Comparative analysis of various tumor-associated antigenspecific T cell responses in patients with hepatocellular carcinoma (2011)
  • Author(s): 水腰英四郎
  • Organizer: The International Liver Congress 2011 by EASL
  • Place of Presentation: Internationales Congress Centrum (ICC)
  • Year and Date: 2011-04-11
• [Presentation] Comparative analysis of various tumor-associated antigen-specific T cell responses in patients with hepatocellular carcinoma (2011)
  • Author(s): 水腰英四郎
  • Organizer: 46th Annual Meeting of the European Association for the Study of the Liver
  • Place of Presentation: Internationales CongressCentrum(ベルリン)
  • Year and Date: 2011-03-31