Immunotherapy using dendritic cell targeting cancer stem cell

• Project/Area Number: 15K10606
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Urology
• Research Institution: Wakayama Medical University
• Principal Investigator: Hara Isao 和歌山県立医科大学, 医学部, 教授 (10263378)
• Co-Investigator(Kenkyū-buntansha): 山上 裕機 和歌山県立医科大学, 医学部, 教授 (20191190) ; 尾島 敏康 和歌山県立医科大学, 医学部, 講師 (60448785)
• Project Period (FY): 2015-04-01 – 2019-03-31
• Project Status: Completed (Fiscal Year 2018)
• Budget Amount: ¥4,550,000 (Direct Cost: ¥3,500,000、Indirect Cost: ¥1,050,000); Fiscal Year 2018: ¥910,000 (Direct Cost: ¥700,000、Indirect Cost: ¥210,000); Fiscal Year 2017: ¥650,000 (Direct Cost: ¥500,000、Indirect Cost: ¥150,000); Fiscal Year 2016: ¥1,040,000 (Direct Cost: ¥800,000、Indirect Cost: ¥240,000); Fiscal Year 2015: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000)
• Keywords: 腫瘍免疫 / 癌幹細胞 / 樹状細胞 / 腫瘍免疫学 / iPS細胞

Outline of Final Research Achievements

Cancer stem cell plays an important role for cancer progression. We have been studying possibility if DNAJB8 which is essential for function of cancer stem cell,
can be a target for tumor immunotherapy. In this study, we tried to establish cytotoxic T cell (CTL) clone recognizing DNAJB8. We selected candidate peptide by peptide binding assay, and succeeded to establish CTL clone recognizing DNAJB8 derived from mononuclear cell of healthy volunteer. This established CTL clone produced interferon by contacting with target cell and showed cytotoxicity against target cell. Since the peptide sequence was identical in both human and mouse, we also could introduce CTL recognizing DNAJB8 in mouse model.

Academic Significance and Societal Importance of the Research Achievements

腎細胞癌は従来の抗癌化学療法に対して抵抗性であり、近年では分子標的薬が施行されるがその成績は満足すべきものではない。免疫チェックポイント阻害剤が一部の腎癌患者に対して優れた抗腫瘍効果を示すことが明らかになってきたが、治療成績の向上のためには腫瘍免疫をさらに賦活化させる方策が考えられる。腎癌の癌幹細胞を標的とした腫瘍免疫療法はこうした観点から従来の腎癌治療の突破口となる可能性を秘めている。

Research Products

• [Journal Article] Cellular stress induces cancer stem-like cells through expression of DNAJB8 by activation of heat shock factor 1 (2018)
  • Author(s): Kusumoto Hiroki、Hirohashi Yoshihiko、Nishizawa Satoshi、Yamashita Masamichi、Yasuda Kazuyo、Murai Aiko、Takaya Akari、Mori Takashi、Kubo Terufumi、Nakatsugawa Munehide、Kanaseki Takayuki、Tsukahara Tomohide、Kondo Toru、Sato Noriyuki、Hara Isao、Torigoe Toshihiko
  • Journal Title: Cancer Science Volume: 109 Issue: 3 Pages: 741-750
  • DOI: 10.1111/cas.13501
  • Peer Reviewed / Open Access
• [Journal Article] Identification of antigenic peptides from novel renal cancer stem-like cell antigen, DNAJB8 (2017)
  • Author(s): Nishizawa S, Hirohashi Y, Kusumoto H, Wakamiya T, Iguchi T, Yamashita S, Iba A, Kikkawa K, Kohjimoto Y, Torigoe T, Hara I
  • Journal Title: Biochem Biophys Res Commun Volume: 494 Issue: 3-4 Pages: 693-699
  • DOI: 10.1016/j.bbrc.2017.10.146
  • Peer Reviewed