Antitumor immunotherapy for small cell lung cancer with Th17 induction

• Project/Area Number: 20590915
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: Respiratory organ internal medicine
• Research Institution: Niigata University
• Principal Investigator: KAGAMU Hiroshi Niigata University, 医歯学系, 講師 (30418686)
• Co-Investigator(Kenkyū-buntansha): NAKATA Kou 新潟大学, 医歯学総合病院, 教授 (80207802) ; YOSHIZAWA Hirohisa 新潟大学, 医歯学総合病院, 准教授 (50282984) ; TANAKA Hiroshi 新潟大学, 医歯学総合病院, 特任助教 (80463991)
• Project Period (FY): 2008 – 2010
• Project Status: Completed (Fiscal Year 2010)
• Budget Amount: ¥4,680,000 (Direct Cost: ¥3,600,000、Indirect Cost: ¥1,080,000); Fiscal Year 2010: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000); Fiscal Year 2009: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000); Fiscal Year 2008: ¥2,210,000 (Direct Cost: ¥1,700,000、Indirect Cost: ¥510,000)
• Keywords: 非閉塞性肺疾患 / 肺線維症 / 呼吸器感染症 / その他 / Th17 / 制御性T細胞 / 小細胞肺癌

Research Abstract

To elucidate the SCLC antigens that are recognized by Th17 cells, we examine surface molecules of SCLC cells and found that the floating SCLC cells express CD133, which is one of putative cancer stem cell (CSC) markers. Proteome analyses revealed DEAD/H (Asp-Glu-Ala-Asp/His) box polypeptide 3, X-linked (DDX3X) as a novel CSC-specific protein. An anti-DDX3X vaccination induced anti-CSC effector T cells that mediated antitumor therapeutic efficacy. DDX3X was highly expressed in human CD133^+ SCLC cells but not in normal epithelial cells. These results indicate that anti-DDX3X, immunotherapy to induce Th17 is a promising treatment option in the clinical setting.

Research Products

• [Journal Article] Clinical responses to EGFR-tyrosine kinase inhibitor retreatmentin non-small cell lung cancer patients who benefited from prioreffective gefitinib therapy : a retrospective analysis (2011)
  • Author(s): Watanabe S, Kgamu H, et al.
  • Journal Title: BMC Cancer Volume: 11 Pages: 1-7
  • Peer Reviewed
• [Journal Article] A prostacyclin agonist with thromboxane inhibitory activity for airway allergic inflammation in mice. (2010)
  • Author(s): Hayashi, M., T.Koya, H.Kawakami, T.Sakagami, T.Hasegawa, H.Kagamu, T.Takada, Y.Sakai, E.Suzuki, E.W.Gelfand, F.Gejyo.
  • Journal Title: Clin Exp Allergy 40 Pages: 317-326
  • Peer Reviewed
• [Journal Article] A prostacyclin agonist with thromboxane inhibitory activity for airway allergic inflammation in mice. (2010)
  • Author(s): Hayashi M, Koya T, Kagamu H, et al.
  • Journal Title: Clin Exp Allergy Pages: 371-326
  • Peer Reviewed
• [Journal Article] A Prostacyclin agonist with thromboxane inhibitory activity for airway allergic inflammation in mice. (2010)
  • Author(s): Hayashi M, Koya T, Kagamu H, et al.
  • Journal Title: Clin Exp Allergy 40 Pages: 317-326
  • Peer Reviewed
• [Journal Article] Class III beta-tubulin expression in tumor cells is correlated with resistance to docetaxel in patients with completely resected non-small-cell lung cancer. (2009)
  • Author(s): Hayashi, Y., H.Kuriyama, H.Umezu, J.Tanaka, T.Yoshimasu, T.Furukawa, H.Tanaka, H.Kagamu, F.Gejyo, H.Yoshizawa.
  • Journal Title: Intern Med 48 Pages: 203-208
  • NAID: 130000122350
  • Peer Reviewed
• [Journal Article] Effect of ciclesonide on bronchial asthma in athletes. (2009)
  • Author(s): Koya, T., T.Hasegawa, J.Tanaka, H.Kawakami, M.Hayashi, H.Kagamu, I.Narita, M.Arakawa, E.Suzuki.
  • Journal Title: J Asthma 46 Pages: 1032-1036
  • Peer Reviewed
• [Journal Article] Anti-interferon-gamma autoantibody in a patient with disseminated Mycobacterium avium complex. (2009)
  • Author(s): Koya, T., C.Tsubata, H.Kagamu, K.Koyama, M.Hayashi, K.Kuwabara, T.Itoh, Y.Tanabe, T.Takada, F.Gejyo.
  • Journal Title: J Infect Chemother 15 Pages: 118-122
  • Peer Reviewed
• [Journal Article] Effect of ciclesonide on bronchial asthma in athletes. (2009)
  • Author(s): Koya T, Kagamu H, et al.
  • Journal Title: J Asthma 46 Pages: 1032-1036
  • Peer Reviewed
• [Journal Article] Anti-interferon-gamma autoantibody in a patient with disseminated Mycobacterium avium complex. (2009)
  • Author(s): Koya T, Kagamu H, et al.
  • Journal Title: J Infect Chemother 15 Pages: 118-122
  • Peer Reviewed
• [Journal Article] Class III beta-tubulin expression in tumor cells is correlated with resistance to docetaxel in patients with completely resected non-small-cell lung cancer. (2009)
  • Author(s): Yoshiki Hayashi, Hideyuki Kuriyama, Hiroshi Umezu, Junta Tanaka, T. Yoshimasu, T. Furukawa, Hiroshi Tanaka, Hiroshi Kagamu, Fumitake Gejyo, Hirohisa Yoshizawa.
  • Journal Title: Internal medicine 48 Pages: 203-208
  • NAID: 130000122350
  • Peer Reviewed
• [Journal Article] Reciprocal CD4^+ T-cell balance of effector CD62L^<low> CD4^+ and CD62L^<high>CD25^+ CD4^+ regulatory T cells in small cell lung cancer reflects disease stage. (2008)
  • Author(s): Koyama, K., H.Kagamu, S.Miura, T.Hiura, T.Miyabayashi, R.Itoh, H. Kuriyama, H.Tanaka, J.Tanaka, H.Yoshizawa, K. Nakata, F.Gejyo
  • Journal Title: Clin Cancer Res 14 Pages: 6770-6779
  • Peer Reviewed
• [Journal Article] Appropriate timing of CD40 ligation for RNA-Pulsed DCs to induce antitumor immunity. (2008)
  • Author(s): Miura, S., H.Kagamu, H.Tanaka, H.Yoshizawa, F.Gejyo.
  • Journal Title: Scand J Immunol 67 Pages: 385-391
  • Peer Reviewed
• [Journal Article] Timing of CD40 Ligation for RNA-Pulsed DCs to Induce Antitumor Immunity. (2008)
  • Author(s): Satoru Miura, Hiroshi KagamuHiroshi Tanaka, Hirohisa Yoshizawa, Fumitake Gejyo
  • Journal Title: Scandinavian journal of immunology. 67 Pages: 385-391
  • Peer Reviewed
• [Journal Article] Reciprocal CD4^+ T-Cell Balance of Effector CD62L^<low> CD4^+ and CD62L^<high>CD25^+ CD4^+ Regulatory T Cells in Small Cell Lung Cancer Reflects Disease Stage. (2008)
  • Author(s): Kenichi Koyama, Hiroshi Kagamu, Satoru Miura, Toru Hiura, Takao Miyabayashi, Ryo Itoh, Hideyuki Kuriyama, Hiroshi Tanaka, Junta Tanaka, Hirohisa Yoshizawa, Koh Nakata, Fumitake Gejyo
  • Journal Title: Clin Cancer Res 14 Pages: 6770-6779
  • Peer Reviewed
• [Presentation] Cancer stem cells express specific immunogenic proteins that induce Th17-dominant immunity. (2010)
  • Author(s): 古塩純、各務博、市川紘将、馬場順子、宮林貴大、渡部聡、田中洋史、田中純太、吉澤弘久、中田光、成田一衛
  • Organizer: 日本癌学会学術総会
  • Place of Presentation: 大阪国際会議場
  • Year and Date: 2010-09-24
• [Presentation] Cancer stem cells express specific immunogenic proteins that induce Th17-dominant immunity (2010)
  • Author(s): 古塩純
  • Organizer: 日本癌学会学術総会
  • Place of Presentation: パシフィコ横浜
  • Year and Date: 2010-09-24
• [Presentation] Cancer stem cells express specific immunogenic proteins that induce Th17-dominant immunity resulting in regression of parentaltumor in vivo. (2010)
  • Author(s): 宮林貴大
  • Organizer: American Association for Cancer Research
  • Place of Presentation: Washington DC, USA
  • Year and Date: 2010-04-20
• [Presentation] Cancer stem cells express specific immunogenic proteins that induce Th17-dominant immunity resulting in regression of parental tumor in vivo. (2010)
  • Author(s): Takao Miyabayashi, Hiroshi Kagamu, Jun Koshio, Kosuke Ichikawa, Junko Baba, Satoshi Watanabe, Hiroshi Tanaka, Junta Tanaka, Hirohisa Yoshizawa, Koh Nakata, Ichiei Narita
  • Organizer: American Association for Cancer Research annual meeting
  • Place of Presentation: Washington DC
• [Presentation] Cancer stem cell targeted immunotherapy mediates potent antitumor reactivity against established parental melanoma (2009)
  • Author(s): 宮林貴大
  • Organizer: 日本癌学会学術総会international session
  • Place of Presentation: パシフィコ横浜
  • Year and Date: 2009-10-31
• [Presentation] Cancer stem cell targeted immunotherapy mediates potent antitumor reactivity against established parental melanoma. (2009)
  • Author(s): 宮林貴大、各務博、小山建一、馬場順子、渡部聡、田中純太、田中洋史、吉澤弘久、中田光、成田一衛
  • Organizer: 日本癌学会学術総会
  • Place of Presentation: パシフィコ横浜(intemational session)
  • Year and Date: 2009-10-01
• [Presentation] DEAD/H (Asp-Glu-Ala-Asp/His) box polypeptide 3, X-linked is a CD133^+ tumor-specific protein and induces antitumor immunity. (2009)
  • Author(s): 宮林貴大, 各務博, 小山建一, 栗山英之, 田中純太, 田中洋史, 吉澤弘久, 中田光, 下条文武
  • Organizer: ECCO 15-34^<th> ESMO Multidisciplinary Congress
  • Place of Presentation: Berlin
• [Presentation] Immunotherapy to eliminate cancer stem cells (2008)
  • Author(s): 宮林貴大、各務博、小山建一、太田毅、栗山英之、田中純太、田中洋史、吉澤弘久、下条文武
  • Organizer: 日本癌学会学術総会
  • Place of Presentation: 名古屋国際会議場(oral session)
  • Year and Date: 2008-10-29
• [Presentation] Immunotherapy to eliminate cancer stem cells(癌幹細胞根絶をめざした抗腫瘍免疫療法) (2008)
  • Author(s): Takao Miyabayashi, Hiroshi Kagamu. Kenichi Koyama, Takeshi Ota, Hideyuki Kuriyama, Junta Tanaka, Hiroshi Tanaka, Hirohisa Yoshizawa, Fumitake Geiyo
  • Organizer: 日本癌学会
  • Place of Presentation: パシフイコ横浜
  • Year and Date: 2008-10-29
• [Presentation] 小細胞肺癌患者末梢血エフェクターCD4+T細胞/制御性T細胞バランスと病期、予後 (2008)
  • Author(s): 小山建一, 各務博, 田中洋史, 栗山英之, 田中純太, 高田俊範, 吉滓弘久, 下条文武
  • Organizer: 日本呼吸器学会
  • Place of Presentation: 神戸コンベンションセンター
  • Year and Date: 2008-06-17
• [Book] 急性腎不全・AKIハンドブック(抗がん剤による急性腎不全) (2010)
  • Author(s): 各務博、西慎一
  • Total Pages: 5
  • Publisher: 中外医学社