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Development of a novel therapeutic approach for pediatric malignant solid tumors using NKT cell-mediated immune system

Research Project

Project/Area Number 23592624
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeMulti-year Fund
Section一般
Research Field Pediatric surgery
Research InstitutionChiba Cancer Center (Research Institute) (2013)
Chiba University (2011-2012)

Principal Investigator

HISHIKI TOMORO  千葉県がんセンター(研究所), 発がん研究グループ, 主任医長 (00375776)

Co-Investigator(Kenkyū-buntansha) YOSHIDA Hideo  千葉大学, 大学院医学研究院, 教授 (60210712)
MOTOHASHI Shinichiro  千葉大学, 大学院医学研究院, 教授 (60345022)
KAMIJO Takehiko  千葉県がんセンター, 発がん研究部, 部長 (90262708)
Project Period (FY) 2011 – 2013
Project Status Completed (Fiscal Year 2013)
Budget Amount *help
¥5,200,000 (Direct Cost: ¥4,000,000、Indirect Cost: ¥1,200,000)
Fiscal Year 2013: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
Fiscal Year 2012: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
Fiscal Year 2011: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
Keywords神経芽腫 / 免疫療法 / NKT細胞 / 小児悪性固形腫瘍
Research Abstract

The prognosis of patients with pediatric malignant solid tumors have dramatically improved, although a part of these tumors are yet aggressive and fatal. Survivors suffer from grave side effects as a result of multimodal therapy, and the QOL of these patients are not satisfactory. In the present preclinical study, we aimed to develop a novel therapeutic approach for these tumors. NKT cells were detected in tumor-burden patients and were expandable in vitro. These cells showed significant cytotoxicity against neuroblastoma cell lines. Clinical implication of NKT mediated immunotherapy is awaited on the basis of these results.

Report

(4 results)
  • 2013 Annual Research Report   Final Research Report ( PDF )
  • 2012 Research-status Report
  • 2011 Research-status Report
  • Research Products

    (33 results)

All 2014 2013 2012 2011 Other

All Journal Article (25 results) (of which Peer Reviewed: 14 results,  Open Access: 2 results) Presentation (8 results)

  • [Journal Article] Novel 1p tumour suppressor Dnmt1- associated protein 1 regulates MYCN/ ataxia telangiectasia mutated/p53 pathway2014

    • Author(s)
      Yamaguchi Y, Takenobu H, Ohira M, Nakazawa A, Yoshida S, Akita N, Shimozato O, Iwama A, Nakagawara A, Kamijo T
    • Journal Title

      Eur J Cancer

      Volume: 50 Pages: 1555-1565

    • Related Report
      2013 Final Research Report
  • [Journal Article] Novel 1p tumour suppressor Dnmt1-associated protein 1 regulates MYCN/ataxia telangiectasia mutated/p53 pathway.2014

    • Author(s)
      Yamaguchi Y, Takenobu H, Ohira M, Nakazawa A, Yoshida S, Akita N, Shimozato O, Iwama A, Nakagawara A, Kamijo T.
    • Journal Title

      Eur J Cancer

      Volume: 50 Issue: 8 Pages: 1555-1565

    • DOI

      10.1016/j.ejca.2014.01.023

    • Related Report
      2013 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Current therapeutic strategies for childhood hepatic tumors : surgical and interventional treatments for hepatoblastoma2013

    • Author(s)
      Hishiki T
    • Journal Title

      Int J Clin Oncol

      Volume: 18 Pages: 962-968

    • Related Report
      2013 Final Research Report
  • [Journal Article] Optimal surgical treatment and urological outcomes in boys with pelvic and urogenital rhabdomyosarcomas and soft tissue sarcomas2013

    • Author(s)
      Hishiki T, Saito T, Mitsunaga T, Nakata M, Terui E, Komatsu S, Mise N, Harada K, Iwai J, Higashimoto Y, Okimoto Y, Kakuda H, Ochiai H, Hino M, Homma S, Osa Y, Yoshida H
    • Journal Title

      Pediatr Surg Int

      Volume: 29 Pages: 1077-1082

    • Related Report
      2013 Final Research Report
  • [Journal Article] NKT Cells as an Ideal Anti- Tumor Immunotherapeutic2013

    • Author(s)
      Fujii SI, Shimizu K, Okamoto Y, Kunii N, Nakayama T, Motohashi S, Taniguchi M
    • Journal Title

      Front Immunol

      Volume: 2 Pages: 409-409

    • Related Report
      2013 Final Research Report
  • [Journal Article] Current therapeutic strategies for childhood hepatic tumors: surgical and interventional treatments for hepatoblastoma2013

    • Author(s)
      Hishiki T
    • Journal Title

      International Journal of Clinical Oncology

      Volume: 18 Issue: 6 Pages: 962-968

    • DOI

      10.1007/s10147-013-0625-7

    • Related Report
      2013 Annual Research Report
    • Peer Reviewed
  • [Journal Article] A cisplatin plus pirarubicin-based JPLT2 chemotherapy for hepatoblastoma: experience and future of the Japanese Study Group for Pediatric Liver Tumor (JPLT)2013

    • Author(s)
      Hiyama E, Ueda Y, Onitake Y, Kurihara S, Watanabe K, Hishiki T, Tajiri T, Ida K, Yano M, Kondo S, Oue T; Japanese Study Group for Pediatric Liver Tumor
    • Journal Title

      Pediatric Surgery International

      Volume: 29 Issue: 10 Pages: 1071-1075

    • DOI

      10.1007/s00383-013-3399-0

    • Related Report
      2013 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Optimal surgical treatment and urological outcomes in boys with pelvic and urogenital rhabdomyosarcomas and soft tissue sarcomas.2013

    • Author(s)
      Hishiki T, Saito T, Mitsunaga T, Nakata M, Terui E, Komatsu S, Mise N, Harada K, Iwai J, Higashimoto Y, Okimoto Y, Kakuda H, Ochiai H, Hino M, Homma S, Osa Y, Yoshida H.H
    • Journal Title

      Pediatric Surgery International

      Volume: 29 Issue: 10 Pages: 1077-1082

    • DOI

      10.1007/s00383-013-3400-y

    • Related Report
      2013 Annual Research Report
    • Peer Reviewed
  • [Journal Article] NKT Cells as an Ideal Anti-Tumor Immunotherapeutic.2013

    • Author(s)
      Fujii SI, Shimizu K, Okamoto Y, Kunii N, Nakayama T, Motohashi S, Taniguchi M
    • Journal Title

      Front Immunol

      Volume: 2 Pages: 409-409

    • Related Report
      2013 Annual Research Report
  • [Journal Article] Novel adaptor protein Shf interacts with ALK receptor and negatively regulates its downstream signals in neuroblastoma.2013

    • Author(s)
      Takagi D
    • Journal Title

      Cancer Sci

      Volume: 104 Issue: 5 Pages: 563-572

    • DOI

      10.1111/cas.12115

    • Related Report
      2012 Research-status Report
    • Peer Reviewed
  • [Journal Article] Surgical strategies for unresectable hepato- blastomas2012

    • Author(s)
      Tajiri T, Kimura O, Fumino S, Furukawa T, Iehara T, Souzaki R, Kinoshita Y, Koga Y, Suminoe A, Hara T, Kohashi K, Oda Y, Hishiki T, Hosoi H, Hiyama E, Taguchi T
    • Journal Title

      J Pediatr Surg

      Volume: 47 Pages: 2194-2198

    • Related Report
      2013 Final Research Report
  • [Journal Article] Regulation of memory CD4 T-cell pool size and function by natural killer T cells in vivo2012

    • Author(s)
      Iwamura C, Shinoda K, Endo Y, Watanabe Y, Tumes DJ, Motohashi S, Kawahara K, Kinjo Y, Nakayama T
    • Journal Title

      Proc Natl Acad Sci U S A

      Volume: 109 Pages: 16992-16997

    • Related Report
      2013 Final Research Report
  • [Journal Article] Accumulation of activated invariant natural killer T cells in the tumor microenvironment afterα- galactosylceramide - pulsed antigen presenting cells2012

    • Author(s)
      Nagato K, Motohashi S, Ishibashi F, Okita K, Yamasaki K, Moriya Y, Hoshino H, Yoshida S, Hanaoka H, Fujii S, Taniguchi M, Yoshino I, Nakayama T
    • Journal Title

      J Clin Immunol

      Volume: 32 Pages: 1071-1081

    • Related Report
      2013 Final Research Report
  • [Journal Article] Surgical strategies for unresectable hepatoblastomas.2012

    • Author(s)
      Tajiri T, Hiyama E, et al
    • Journal Title

      Journal of Pediatric Surgery.

      Volume: 47 Issue: 12 Pages: 2194-2198

    • DOI

      10.1016/j.jpedsurg.2012.09.006

    • Related Report
      2012 Research-status Report
    • Peer Reviewed
  • [Journal Article] Regulation of memory CD4 T-cell pool size and function by natural killer T cells in vivo. 109(42) : 16992-16997 (2012).2012

    • Author(s)
      Iwamura, C., Shinoda, K., Endo, Y., Watanabe, Y., Tumes, J. D., Motohashi, S., Kawahara, K., Kinjo, Y., and Nakayama, T.
    • Journal Title

      Proc. Natl. Acad. Sci. USA

      Volume: 109 Issue: 42 Pages: 16992-16997

    • DOI

      10.1073/pnas.1203494109

    • Related Report
      2012 Research-status Report
    • Peer Reviewed
  • [Journal Article] The transcription factor Sox4 is a downstream target of signaling by the cytokine TGF-・ and suppresses TH2 differentiation2012

    • Author(s)
      Kuwahara, M., Yamashita, M., Shinoda, K., Tofukuji, S., Onodera, A., Shinnakasu, R., Motohashi, S., Hosokawa, H., Tumes, D., Iwamura, C., Lefebvre, V., and Nakayama, T.
    • Journal Title

      Nat. Immunol

      Volume: 13(8) Issue: 8 Pages: 778-786

    • DOI

      10.1038/ni.2362

    • Related Report
      2012 Research-status Report
    • Peer Reviewed
  • [Journal Article] Accumulation of Activated Invariant Natural Killer T Cells in the Tumor Microenvironment after α-Galactosylceramide-Pulsed Antigen Presenting Cells.2012

    • Author(s)
      Nagato K, Motohashi S, Ishibashi F, Okita K, Yamasaki K, Moriya Y, Hoshino H, Yoshida S, Hanaoka H, Fujii SI, Taniguchi M, Yoshino I, Nakayama T.
    • Journal Title

      J Clin Immunol.

      Volume: 32 Issue: 5 Pages: 1071-81

    • DOI

      10.1007/s10875-012-9697-9

    • Related Report
      2012 Research-status Report
    • Peer Reviewed
  • [Journal Article] Murine Schnurri-2 controls Natural Killer cell function and lymphoma development2012

    • Author(s)
      Yamashita, J., Iwamura, C., Mitsumori, K., Hosokawa, H., Sasaki, T., Takahashi, M., Tanaka, H., Kaneko, K., Hanazawa, A., Watanabe, Y., Shinoda, K., Tumes, D., Motohashi, S., Nakayama, T.
    • Journal Title

      Leuk.Lymphoma

      Volume: 53 Issue: 3 Pages: 479-486

    • DOI

      10.3109/10428194.2011.625099

    • Related Report
      2012 Research-status Report
    • Peer Reviewed
  • [Journal Article] NLRR1 enhances EGF-mediated MYCN induction in neuroblastoma and accelerates tumor growth in vivo.2012

    • Author(s)
      Hossain S
    • Journal Title

      Cancer Res

      Volume: 72 Issue: 17 Pages: 4587-4596

    • DOI

      10.1158/0008-5472.can-12-0943

    • Related Report
      2012 Research-status Report
    • Peer Reviewed
  • [Journal Article] Anti-tumor immune responses induced by iNKT cell-based immunotherapy for lung cancer and head and neck cancer2011

    • Author(s)
      Motohashi S, et al
    • Journal Title

      Clin Immunol

      Volume: 140 Pages: 167-176

    • Related Report
      2013 Final Research Report
  • [Journal Article] Induction of NKT cell-specific immune responses in cancer tissues after NKT cell-targeted adoptive immunotherapy2011

    • Author(s)
      Yamasaki K, Motohashi S, et al
    • Journal Title

      Clin Immunol

      Volume: 138 Pages: 256-265

    • Related Report
      2013 Final Research Report
  • [Journal Article] Migration and immunological reaction after the administration ofαGalCer-pulsed antigen-presenting cells into the submucosa of patients with head and neck cancer2011

    • Author(s)
      Kurosaki M, Motohashi S, et al
    • Journal Title

      Cancer Immunol Immunother

      Volume: 60 Pages: 207-215

    • Related Report
      2013 Final Research Report
  • [Journal Article] Anti-tumor immune responses induced by iNKT cell-based immunotherapy for lung cancer and head and neck cancer.2011

    • Author(s)
      Motohashi et al
    • Journal Title

      Clin Immunol.

      Volume: 140 Pages: 167-176

    • Related Report
      2011 Research-status Report
    • Peer Reviewed
  • [Journal Article] Induction of NKT cell-specific immune responses in cancer tissues after NKT cell-targeted adoptive immunotherapy.2011

    • Author(s)
      Yamasaki K, Motohashi S, et al
    • Journal Title

      Clin Immunol.

      Volume: 138 Pages: 255-265

    • Related Report
      2011 Research-status Report
    • Peer Reviewed
  • [Journal Article] Migration and immunological reaction after the administration of αGalCer-pulsed antigen-presenting cells into the submucosa of patients with head and neck cancer.2011

    • Author(s)
      Kurosaki M, Motohashi S, et al
    • Journal Title

      Cancer Immunol Immunother

      Volume: 60 Pages: 207-215

    • Related Report
      2011 Research-status Report
    • Peer Reviewed
  • [Presentation] 小児悪性固形腫瘍に対するNKT細胞系を用いた新規免疫療法の開発研究2013

    • Author(s)
      菱木知郎
    • Organizer
      第50回日本小児外科学会学術集会
    • Year and Date
      2013-05-29
    • Related Report
      2013 Final Research Report
  • [Presentation] 小児悪性固形腫瘍に対するNKT細胞系を用いた新規免疫療法の開発研究2013

    • Author(s)
      菱木知郎
    • Organizer
      第50回 日本小児外科学会学術集会
    • Place of Presentation
      東京
    • Related Report
      2013 Annual Research Report
  • [Presentation] 神経芽腫細胞に対するNKT細胞によるADCC増強効果の検討2013

    • Author(s)
      三瀬 直子, 菱木 知郎, 斎藤 武, 照井 慶太, 光永 哲也, 中田 光政, 國井 直樹, 藤川 陽, 堀中 敦史, 鎌田 稔子, 蒔田 勇治, 内田 亮介, 伊原 史英, 吉田 英生, 本橋 新一郎
    • Organizer
      第55回 日本小児血液・がん学会学術集会
    • Place of Presentation
      福岡
    • Related Report
      2013 Annual Research Report
  • [Presentation] Review of surgical treatment in patients enrolled in the JNBSG high risk neuroblastoma clinical trial (A phase II study of multidisciplinary approach to establish standard treatment for advanced neuroblastoma)2012

    • Author(s)
      菱木知郎
    • Organizer
      A report from Japan Neuroblatoma Study Group (JNBSG).第54回日本小児血液・がん学会学術集会
    • Year and Date
      2012-12-10
    • Related Report
      2013 Final Research Report
  • [Presentation] 小児悪性固形腫瘍に対するNKT細胞系を用いた新規免疫療法の開発研究2012

    • Author(s)
      菱木知郎
    • Organizer
      第54回日本小児血液・がん学会学術集会
    • Year and Date
      2012-12-10
    • Related Report
      2013 Final Research Report
  • [Presentation] 神経芽腫細胞に対するNKT細胞によるADCC増強効果の検討

    • Author(s)
      三瀬直子, 菱木知郎, 斎藤武, 照井慶太, 光永哲也, 中田光政, 國井直樹, 藤川陽, 堀中敦史, 鎌田稔子, 蒔田勇治, 内田亮介, 伊原史英, 吉田英生, 本橋新一郎
    • Organizer
      第55回日本小児血液・がん学会学術集会
    • Related Report
      2013 Final Research Report
  • [Presentation] Review of surgical treatment in patients enrolled in the JNBSG high risk neuroblastoma clinical trial (A phase II study of multidisciplinary approach to establish standard treatment for advanced neuroblastoma) ̶ A report from Japan Neuroblatoma Study Group (JNBSG)

    • Author(s)
      菱木 知郎
    • Organizer
      第54回 日本小児血液・がん学会学術集会
    • Place of Presentation
      横浜
    • Related Report
      2012 Research-status Report
  • [Presentation] 小児悪性固形腫瘍に対する NKT 細胞系を用いた新規免疫療法の開発研究

    • Author(s)
      菱木 知郎
    • Organizer
      第54回 日本小児血液・がん学会学術集会
    • Place of Presentation
      横浜
    • Related Report
      2012 Research-status Report

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Published: 2011-08-05   Modified: 2019-07-29  

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