Anti-tumor immunotherapy targeting a cancer stem cell-specific protein for small cell lung cancer

• Project/Area Number: 23591141
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Respiratory organ internal medicine
• Research Institution: Niigata University
• Principal Investigator: KAGAMU HIROSHI 新潟大学, 医歯学系, 講師 (30418686)
• Co-Investigator(Kenkyū-buntansha): NAKATA Ko 新潟大学, 医歯学総合病院, 教授 (80207802) ; TSUCHIDA Masanori 新潟大学, 医歯学系, 教授 (60293221)
• Project Period (FY): 2011 – 2013
• Project Status: Completed (Fiscal Year 2013)
• Budget Amount: ¥5,200,000 (Direct Cost: ¥4,000,000、Indirect Cost: ¥1,200,000); Fiscal Year 2013: ¥1,040,000 (Direct Cost: ¥800,000、Indirect Cost: ¥240,000); Fiscal Year 2012: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000); Fiscal Year 2011: ¥2,470,000 (Direct Cost: ¥1,900,000、Indirect Cost: ¥570,000)
• Keywords: DDX3X / 小細胞肺癌 / 抗腫瘍免疫療法 / メラノーマ / CD4＋ T細胞 / 国債情報交換 / 国際情報交流

Research Abstract

[Background] Small cell lung cancer (SCLC) possesses high tendency to disseminate. However, SCLC patients with paraneoplastic syndrome mediated by immunity against onconeural antigens remain in limited-stage disease (LD) without distant metastases. We previously reported that DEAD/H (Asp-Glu-Ala-Asp/His) box polypeptide 3, X-linked (DDX3X) is an immunogenic protein preferentially expressed in CD133+ murine melanoma cells exhibiting biological CSC features. [Results] Five of 15 LD-SCLC patients possessed DDX3X-responsive effector T cells. CD4+ effector T cells obtained from peripheral blood of 5 LD-SCLC secreted significantly more IFNgamma upon DDX3X antigen stimulation in the presence of CD11c+ autologous dendritic cells. effector T cells from one LD-SCLC patient responded to DDX3X. In contrast, effector T cells obtained from ED-SCLC patients or healthy volunteers never responded to DDX3X. DDX3X-primed CD4+ T cells mediated potent antitumor therapeutic efficacy in murine models.

Research Products

• [Journal Article] DEAD/H (Asp-Glu-Ala-Asp/His) box polypeptide 3, X-linked is an immunogenic target of cancer stem cells (2013)
  • Author(s): Koshio, J. Kagamu, H. Nozaki, K. Saida, Y. Tanaka, T. Shoji, S. Igarashi, N. Miura, S. Okajima, M. Watanabe, S. Yoshizawa, H. Narita, I.
  • Journal Title: Cancer Immunol Immunother Volume: 62 Issue: 10 Pages: 1619-28
  • DOI: 10.1007/s00262-013-1467-x
  • Peer Reviewed
• [Journal Article] mTOR inhibitors control erlotinib-resistance of EGFR mutant lung cancer cells triggered by HGF. (2013)
  • Author(s): Ishikawa D, Yano S, et al.
  • Journal Title: PLoS ONE Volume: 8 Issue: 5 Pages: e62104-e62104
  • DOI: 10.1371/journal.pone.0062104
  • Peer Reviewed
• [Journal Article] IL-17 eliminates therapeutic effects of oral tolerance in murine airway allergic inflammation. (2012)
  • Author(s): Kawakami, H., Koya, T., Kagamu, H., Kimura, Y., Sakamoto, H., Yamabayashi, C., Furukawa, T., Sakagami, T., Miyabayashi, T., Hasegawa, T., Suzuki, E. and Narita, I.
  • Journal Title: Clin Exp Allergy Volume: 42 Issue: 6 Pages: 946-957
  • DOI: 10.1111/j.1365-2222.2012.04006.x
  • Peer Reviewed
• [Journal Article] Epitope diversification driven by non-tumor epitope-specific Th1 and Th17 mediates potent antitumor reactivity. (2012)
  • Author(s): Ichikawa, K., Kagamu, H., Koyama, K., Miyabayashi, T., Koshio, J., Miura, S., Watanabe, S., Yoshizawa, H. and Narita, I.
  • Journal Title: Vaccine Volume: 30 Issue: 43 Pages: 6190-7
  • DOI: 10.1016/j.vaccine.2012.07.060
  • Peer Reviewed
• [Journal Article] Depletion of radio-resistant regulatory T cells enhances antitumor immunity during recovery from lymphopenia. (2012)
  • Author(s): Baba, J., Watanabe, S., Saida, Y., Tanaka, T., Miyabayashi, T., Koshio, J., Ichikawa, K., Nozaki, K., Miura, S., Tanaka, H., Tanaka, J., Kagamu, H., Yoshizawa, H., Nakata, K. and Narita, I.
  • Journal Title: Blood Volume: 120 Issue: 12 Pages: 2417-27
  • DOI: 10.1182/blood-2012-02-411124
  • Peer Reviewed
• [Journal Article] Vaccination with CD133(+) melanoma induces specific Th17 and Th1 cell-mediated antitumor reactivity against parental tumor (2011)
  • Author(s): Miyabayashi T, Yoshizawa H, et al
  • Journal Title: Cancer Immunol Immunother Volume: 11 Issue: 11 Pages: 1597-608
  • DOI: 10.1007/s00262-011-1063-x
  • Peer Reviewed
• [Journal Article] Clinical responses to EGFR-tyrosine kinase inhibitor retreatment in non-small cell lung cancer patients who benefited from prior effective gefitinib therapy: a retrospective analysis (2011)
  • Author(s): Watanabe, S. Tanaka, J. Ota, T. Kondo, R. Tanaka, H. Kagamu, H. Ichikawa, K. Koshio, J. Baba, J. Miyabayashi, T. Narita, I. Yoshizawa, H.
  • Journal Title: BMC Cancer Volume: 11 Issue: 1 Pages: 1-1
  • DOI: 10.1186/1471-2407-11-1
  • Peer Reviewed
• [Presentation] DEAD/H (Asp-Glu-Ala-Asp/His) box polypeptide 3, X-linked plays oncogenic roles to induce cancer stem cell-like properties (2013)
  • Author(s): Koichiro Nozaki, Hiroshi Kagamu, Satoshi Shoji, Natsue Ikarashi, Masaaki Okajima, Satoru Miura, Satoshi Watanabe, Hirohisa Yoshizawa, Ichiei Narita
  • Organizer: American Association for Cancer Research
  • Place of Presentation: Washington DC, USA
• [Presentation] DDX3X plays a critical role in a novel EGFR-TKI resistance mechanism correlating with CSC-like properties. (2013)
  • Author(s): Koichiro Nozaki, Hiroshi Kagamu, Jun Koshio, Kosuke Ichikawa, Yu Saida, Tomohiro Tanaka, Satoshi Watanabe, Hirohisa Yoshizawa, and Ichiei Narita
  • Organizer: 日本癌学会
  • Place of Presentation: 横浜
• [Presentation] DEAD/H (Asp-Glu-Ala-Asp/His) box polypeptide 3, X-linked plays an oncogenic roles to induce cancer stem cell-like properties (2012)
  • Author(s): Koichiro Nozaki1, Hiroshi Kagamu1, Yu Saida1, Tomohiro Tanaka1, Satoshi Watanabe2, Hirohisa Yoshizawa2, and Ichiei Narita1
  • Organizer: European Society for Medical Oncology
  • Place of Presentation: Vienna, Austria
• [Presentation] Oncogenic roles of DEAD/H (Asp-Glu-Ala-Asp/His) box polypeptide 3, X-linked (2012)
  • Author(s): Koichiro Nozaki1, Hiroshi Kagamu1, Yu Saida1, Tomohiro Tanaka1, Satoshi Watanabe2, Hirohisa Yoshizawa2, and Ichiei Narita1
  • Organizer: 日本癌学会
  • Place of Presentation: 札幌
• [Presentation] DEAD/H (Asp-Glu-Ala-Asp/His) box polypeptide 3, X-linked is a CD133+ tumor-specific protein and induces antitumor immunity (2011)
  • Author(s): Jun Koshio1, Hiroshi Kagamu1, et al.
  • Organizer: AACR
  • Place of Presentation: Orange County convention center (Orland, Florida, USA)
• [Presentation] DEAD/H (Asp-Glu-Ala-Asp/His) box polypeptide 3, X-linked is a CD133+ tumor-specific protein and induces antitumor immunity (2011)
  • Author(s): Jun Koshio1, Hiroshi Kagamu1, et al.
  • Organizer: 日本癌学会
  • Place of Presentation: 名古屋国際会議場（名古屋市）
• [Patent(Industrial Property Rights)] 癌幹細胞に発現する分子をターゲットとした癌を診断、治療する方法 (2013)
  • Inventor(s): 各務博、成田一衛、林隆史、後藤義博
  • Industrial Property Rights Holder: 各務博、成田一衛、林隆史、後藤義博
  • Industrial Property Rights Type: 特許
  • Filing Date: 2013-09-03
  • Overseas
• [Patent(Industrial Property Rights)] 癌幹細胞に発現する分子をターゲットとした癌を診断、治療する方法 (2012)
  • Inventor(s): 各務博、成田一衛、林隆史、後藤義博
  • Industrial Property Rights Holder: 各務博、成田一衛、林隆史、後藤義博
  • Industrial Property Rights Type: 特許
  • Filing Date: 2012-09-04
  • Acquisition Date: 2013-09-03
  • Overseas