Development of NKT cell-based cancer immunotherapy for glioblastoma

• Project/Area Number: 17K16625
• Research Category: Grant-in-Aid for Young Scientists (B)
• Allocation Type: Multi-year Fund
• Research Field: Neurosurgery
• Research Institution: Chiba University
• Principal Investigator: Hara Ayaka 千葉大学, 医学部附属病院, 医員 (90792705)
• Project Period (FY): 2017-04-01 – 2019-03-31
• Project Status: Completed (Fiscal Year 2018)
• Budget Amount: ¥4,030,000 (Direct Cost: ¥3,100,000、Indirect Cost: ¥930,000); Fiscal Year 2018: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000); Fiscal Year 2017: ¥2,210,000 (Direct Cost: ¥1,700,000、Indirect Cost: ¥510,000)
• Keywords: 膠芽腫 / NKT細胞 / 免疫治療

Outline of Final Research Achievements

This study showed that CD1d, an antigen-presenting molecule for invariant natural killer T (iNKT) cells, was expressed on several patient glioblastoma cells. CD1d-expressing glioblastoma cells presented glycolipid antigens to induce iNKT cell-mediated cytotoxicity in vitro. Moreover, intracranial administration of human iNKT cells caused a regression in orthotopic CD1d-expressing human glioblastoma xenografts in immunodeficient mice. Thus, CD1d expression may represent a novel target for NKT cell-based precision cancer immunotherapy for glioblastoma patients.

Academic Significance and Societal Importance of the Research Achievements

予後不良な膠芽腫に対する新規治療法の開発は困難を極めている。本研究では、膠芽腫患者の腫瘍組織を解析し、Natural Killer T(NKT)細胞に対する特異的な抗原提示分子であるCD1d陽性の腫瘍細胞が存在することを見出した。さらに免疫不全マウスにCD1d陽性細胞株を同所移植して作成した膠芽腫モデルに対して、NKT細胞とNKT細胞の代表的な糖脂質抗原であるα-GalCerを投与する免疫治療実験を行い、抗腫瘍効果を認めた。これらの結果は、膠芽腫におけるCD1d発現は、NKT細胞を用いた膠芽腫プレシジョン医療の新規標的となりうることを示している。

Research Products

• [Journal Article] Eighty percent survival rate at 15 years for 1p/19q co-deleted oligodendroglioma treated with upfront chemotherapy irrespective of tumor grade (2019)
  • Author(s): Yasuo Iwadate, Tomoo Matsutani, Ayaka Hara, Seiichiro Hirono, Shiro Ikegami, Masayoshi Kobayashi, Daisuke Ito, Daisuke Kawauchi, Kentaro Horiguchi, Ado Tamiya, Yoshinori Higuchi
  • Journal Title: Journal of Neuro-Oncology Volume: 141 Issue: 1 Pages: 205-211
  • DOI: 10.1007/s11060-018-03027-5
  • Peer Reviewed / Open Access
• [Journal Article] Real-time methylation-specific PCR for the evaluation of methylation status of MGMT gene in glioblastoma. (2018)
  • Author(s): Masaki Yoshioka, Tomoo Matsutani, Ayaka Hara, Seiichiro Hirono, Takaki Hiwasa, Masaki Takiguchi, Yasuo Iwadate
  • Journal Title: Oncotarget Volume: Vol. 9, (No. 45) Issue: 45 Pages: 27728-27735
  • DOI: 10.18632/oncotarget.25543
  • Peer Reviewed / Open Access
• [Presentation] 膠芽腫に対するNKT細胞を用いた免疫治療の確立 (2018)
  • Author(s): 原彩佳、那須亮、伊原史英、髙見真理子、廣野誠一郎、松谷智郎、本橋新一郎、岩立康男
  • Organizer: 第13回 Chiba neuroresearch meeting
• [Presentation] 膠芽腫に対するNKT細胞を用いた免疫治療の確立 (2018)
  • Author(s): 原 彩佳
  • Organizer: 第13回 Chiba neuroresearch meeting