Development of a novel anti-cancer immune therapy using the synthetic oligonucleotide containing poly-G motif

• Project/Area Number: 26830111
• Research Category: Grant-in-Aid for Young Scientists (B)
• Allocation Type: Multi-year Fund
• Research Field: Tumor therapeutics
• Research Institution: Yokohama City University
• Principal Investigator: Kobayashi Nobuaki 横浜市立大学, 附属市民総合医療センター, 講師 (60468155)
• Research Collaborator: SHIBATA Yuji 横浜市立大学, 大学院医学研究科・呼吸器病学教室, 非常勤診療医 ; SHINKAI Masaharu 横浜市立大学, 大学院医学研究科・呼吸器病学教室, 准教授 ; KUDO Makoto 横浜市立大学, 附属市民総合医療センター・呼吸器病センター, 准教授 ; KANEKO Takeshi 横浜市立大学, 大学院医学研究科・呼吸器病学教室, 教授 ; SHIROTA Hidekazu 東北大学, 大学院医学研究科・腫瘍内科学教室, 講師
• Project Period (FY): 2014-04-01 – 2017-03-31
• Project Status: Completed (Fiscal Year 2016)
• Budget Amount: ¥3,640,000 (Direct Cost: ¥2,800,000、Indirect Cost: ¥840,000); Fiscal Year 2016: ¥1,040,000 (Direct Cost: ¥800,000、Indirect Cost: ¥240,000); Fiscal Year 2015: ¥1,040,000 (Direct Cost: ¥800,000、Indirect Cost: ¥240,000); Fiscal Year 2014: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
• Keywords: poly G ODN / 合成オリゴヌクレオチド / 抗癌免疫療法 / M1マクロファージ / 樹状細胞 / 抗腫瘍免疫 / 免疫療法 / 腫瘍免疫 / 抗腫瘍免疫活性 / poly-G ODN

Outline of Final Research Achievements

Synthetic oligonucleotides (ODN) containing specific sequences have an immunomodulatory effect. We previously reported that a novel poly-G ODN has an anti-tumor immune effect in a tumor-bearing murine model. Here, we identified poly-G ODN-induced T cell proliferation and production of interferon-gamma through the enhancement of monocyte maturation in human mononuclear cells isolated from the peripheral blood or from the malignant pleural effusion of lung cancer patients. Poly-G ODN also induces the maturation of human monocytes into M1 macrophages through the phosphorylation of STAT1. This mechanism of poly-G ODN in humans is unique from that reported previously in mice for some ODNs containing three guanosines at the 3' tail. Further studies are ongoing to establish a novel anti-cancer immunotherapy for lung cancer with poly-G ODN.

Research Products

• [Presentation] Poly G oligonucleotide enhances anti-tumor immune response among the patients with primary lung cancer (2017)
  • Author(s): Nobuaki Kobayashi
  • Organizer: American Association for Cancer Research Annual Meeting 2017
  • Place of Presentation: Washington D.C., USA
  • Year and Date: 2017-04-01
  • Int'l Joint Research
• [Presentation] poly G ODNのヒトにおける抗腫瘍免疫反応の検討 (2016)
  • Author(s): 柴田 祐司
  • Organizer: 第57回日本肺癌学会学術総会
  • Place of Presentation: 福岡国際会議場
  • Year and Date: 2016-12-19