Identification of the HSP70 peptide for the development of cancer immunetherapy

• Project/Area Number: 26670606
• Research Category: Grant-in-Aid for Challenging Exploratory Research
• Allocation Type: Multi-year Fund
• Research Field: Digestive surgery
• Research Institution: Yamaguchi University
• Principal Investigator: OKA Masaaki 山口大学, その他部局等, 学長 (70144946)
• Co-Investigator(Kenkyū-buntansha): YOSHIMURA Kiyoshi 国立がん研究センター, 先端医療開発センター・免疫療法開発分野, 分野長 (30346564) ; TSUNEDOMI Ryouichi 山口大学, 大学院医学系研究科, 助教 (10420514)
• Project Period (FY): 2014-04-01 – 2016-03-31
• Project Status: Completed (Fiscal Year 2015)
• Budget Amount: ¥3,640,000 (Direct Cost: ¥2,800,000、Indirect Cost: ¥840,000); Fiscal Year 2015: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000); Fiscal Year 2014: ¥2,080,000 (Direct Cost: ¥1,600,000、Indirect Cost: ¥480,000)
• Keywords: 肝細胞癌 / ワクチン療法 / HSP70 / エピトープペプチド / 免疫療法

Outline of Final Research Achievements

We identified the Heat Shock Protein (HSP) 70 as a specific antigen of hepatocellular carcinoma. Furthermore, the phase I study of HSP70-mRNA introduced dendritic cells therapy showed the safety and efficacy. In this study, we tried to identify the HSP70 peptide sequence, which can induce the anti-tumor response, in order to the development of useful peptide vaccine therapy for cancer. Candidate HSP70 peptides predicted as multi-HLA binding potency were confirmed by ELISpot assay and ELISA for IFN-gamma production. The safty of the peptides were examined in rats and dogs. We started a clinical trial of first in Human HSP70 peptide immunetherapy for several cancers.

Research Products

• [Journal Article] Expression of mucin 1 possessing a 3'-sulfated core1 in recurrent and metastatic breast cancer. (2015)
  • Author(s): Ideo H, Hinoda Y, Sakai K, Hoshi I, Yamamoto S, Oka M, Maeda K, Maeda N, Hazama S, Amano J, Yamashita K.
  • Journal Title: International Journal of Cancer Volume: 137 Issue: 7 Pages: 00-00
  • DOI: 10.1002/ijc.29520
  • Peer Reviewed / Acknowledgement Compliant
• [Journal Article] Dendritic cells transfected with heat-shock protein 70 messenger RNA for patients with hepatitis C virus-related hepatocellular carcinoma: a phase 1 dose escalation clinical trial. (2015)
  • Author(s): Maeda Y, Yoshimura K, Matsui H, Shindo Y, Tamesa T, Tokumitsu Y, Hashimoto N, Tokuhisa Y, Sakamoto K, Sakai K, Suehiro Y, Hinoda Y, Tamada K, Yoshino S, Hazama S, Oka M.
  • Journal Title: Cancer Immunol. Immunother. Volume: 64(8) Issue: 8 Pages: 1047-56
  • DOI: 10.1007/s00262-015-1709-1
  • Peer Reviewed
• [Journal Article] Preoperative serum methylation signature as prognostic tool after curative hepatectomy in patients with hepatocellular carcinoma. (2015)
  • Author(s): Kanekiyo S, Iizuka N, Tsunedomi R, Tokumitsu Y, Hashimoto N, Tokuhisa Y, Maeda Y, Iida M, Sakamoto K, Tamesa T, Fujita Y, Yoshino S, Hazama S, Hamamoto Y, Oka M.
  • Journal Title: Anticancer Res. Volume: 35 Pages: 997-1007
  • Peer Reviewed / Open Access
• [Journal Article] Cancer stem-like sphere cells induced from de-differentiated hepatocellular carcinoma-derived cell lines possess the resistance to anti-cancer drugs (2014)
  • Author(s): Noriaki Hashimoto, Ryouichi Tsunedomi, Kiyoshi Yoshimura, Yusaku Watanabe, Shoichi Hazama, and Masaaki Oka
  • Journal Title: BMC Cancer Volume: 14 Issue: 1 Pages: 722-722
  • DOI: 10.1186/1471-2407-14-722
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Presentation] 肝転移能亢進を示す癌幹細胞様細胞における分子標的の探索 (2015)
  • Author(s): 恒富 亮一、松隈 聰、硲 彰一、岡 正朗、永野 浩昭
  • Organizer: 第26回日本消化器癌発生学会総会
  • Place of Presentation: 米子全日空ホテル (鳥取県)
  • Year and Date: 2015-11-20
• [Presentation] miR expression of the tumor might be a predictive biomarker for the efficacy of peptide vaccine for colorectal cancer (2015)
  • Author(s): Shoichi Hazama, Yuka Inoue, Shinsuke Kanekiyo, Yoshitaro Shindo, Nobuaki Suzuki, Takao Tamesa, Ryouichi Tsunedomi, Shigeru Takeda, Tomio Ueno, Shigefumi Yoshino, Yusuke Nakamura, Yutaka Kawakami, and Hiroaki Nagano
  • Organizer: 第74回日本癌学会学術総会
  • Place of Presentation: 名古屋国際会議場 (愛知県)
  • Year and Date: 2015-10-10
• [Presentation] Calreticulin is highly expressed in pancreatic cancer stem like cells (2015)
  • Author(s): Satoshi Matsukuma, Kiyoshi Yoshimura, Yusaku Watanabe, Ryoichi Tsunedomi, Moeko Inoue, Tomoko Kondo-Furuya, Atsunori Oga, Tomio Ueno, Shigefumi Yoshino, Shoichi Hazama, Hiroshi Ito, and Hiroaki Nagano
  • Organizer: 第74回日本癌学会学術総会
  • Place of Presentation: 名古屋国際会議場 (愛知県)
  • Year and Date: 2015-10-08
• [Presentation] Up-regulation of antioxidant ability and HIF1 regulated genes in hepatocellular carcinoma stem-like sphere cells (2015)
  • Author(s): Ryouichi Tsunedomi, Kiyoshi Yoshimura, Shoichi Hazama, and Masaaki Oka
  • Organizer: 第74回日本癌学会学術総会
  • Place of Presentation: 名古屋国際会議場 (愛知県)
  • Year and Date: 2015-10-08
• [Presentation] Cancer-stem like細胞の解析による術後肝内再発抑制に向けた分子標的の探索 (2015)
  • Author(s): 恒富 亮一、松隈 聰、吉村 清、坂本 和彦、爲佐 卓夫、硲 彰一、岡 正朗
  • Organizer: 第24回癌病態治療研究会
  • Place of Presentation: 日光千姫物語(栃木県)
  • Year and Date: 2015-06-26
• [Presentation] 低分化型肝細胞癌細胞株から誘導した癌幹細胞様Sphere 細胞 (2014)
  • Author(s): 恒富亮一、吉村清、硲彰一、岡正朗
  • Organizer: 第73回日本癌学会学術総会
  • Place of Presentation: パシフィコ横浜
  • Year and Date: 2014-09-25
• [Presentation] 肝細胞癌（HCC）に対するHSP70-mRNA 導入樹状細胞療法 (2014)
  • Author(s): 松井 洋人、硲 彰一、松隈 聰、新藤芳太郎、徳光 幸生、徳久 善弘、飯田 通久、坂本 和彦、鈴木 伸明、吉村 清、為佐 卓夫、上野 富雄、吉野 茂文、岡 正朗
  • Organizer: 第18回日本がん免疫学会総会
  • Place of Presentation: ひめぎんホール
  • Year and Date: 2014-07-31