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Development of novel immunotherapy against malignant glioma

Research Project

Project/Area Number 25670613
Research Category

Grant-in-Aid for Challenging Exploratory Research

Allocation TypeMulti-year Fund
Research Field Neurosurgery
Research InstitutionTohoku University

Principal Investigator

SAITO RYUTA  東北大学, 医学(系)研究科(研究院), 助教 (10400243)

Co-Investigator(Kenkyū-buntansha) ISI Nato  東北大学, 大学院医学系研究科, 教授 (60291267)
菊地 利明  東北大学, 医学(系)研究科(研究院), 非常勤講師 (10280926)
Co-Investigator(Renkei-kenkyūsha) KIKUCHI Toshiaki  東北大学, 大学院医学系研究科, 非常勤講師 (10280926)
Project Period (FY) 2013-04-01 – 2015-03-31
Project Status Completed (Fiscal Year 2014)
Budget Amount *help
¥3,770,000 (Direct Cost: ¥2,900,000、Indirect Cost: ¥870,000)
Fiscal Year 2014: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
Fiscal Year 2013: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000)
Keywords腫瘍ワクチン / 脳腫瘍 / 免疫治療 / 共刺激因子 / グリオーマ / サイトカイン / OX40 / CD40
Outline of Final Research Achievements

In the preceding study, we attempted to develop the new immunotherapeutic strategy using one of the costimulatory molecule, OX40. In the present study, we attempted to augment the efficacy of OX40 stimulation by adding it to subcutaneous tumor vaccination therapy. However, during our effort to augment the efficacy by adding similar costimulation molecule, CD40, we realized that CD40 evokes stronger antitumor effect than OX40. Therefore, we concentrated on CD40 and tried to develop effective immunotherapeutic strategy using this molecule. From analyses of clinical tumor samples, we demonstrated that gene expression of CD40 and CD40L (ligand) corresponded with the patients’ progression-free and overall survival. Subsequently, we demonstrated the efficacy of CD40 stimulation by adding CD40 agonistic antibody to subcutaneous tumor vaccines. This strategy prolonged the survival of intracranial tumor models in both glioma model and glioma initiating cell derived glioma models.

Report

(3 results)
  • 2014 Annual Research Report   Final Research Report ( PDF )
  • 2013 Research-status Report
  • Research Products

    (8 results)

All 2015 2014 2013

All Journal Article (5 results) (of which Peer Reviewed: 5 results,  Open Access: 2 results,  Acknowledgement Compliant: 2 results) Presentation (3 results) (of which Invited: 2 results)

  • [Journal Article] OX40 ligand expressed in glioblastoma modulates adaptive immunity depending on the microenvironment: a clue for successful immunotherapy.2015

    • Author(s)
      Shibahara I, Saito R, Zhang R, Chonan M, Shoji T, Kanamori M, Sonoda Y, Kumabe T, Kanehira M, Kikuchi T, So T, Watanabe T, Takahashi H, Iwabuchi E, Tanaka Y, Shibahara Y, Sasano H, Ishii N, Tominaga T.
    • Journal Title

      Mol Cancer

      Volume: in press

    • NAID

      120006847260

    • Related Report
      2014 Annual Research Report
    • Peer Reviewed / Open Access / Acknowledgement Compliant
  • [Journal Article] Association between molecular alterations and tumor location and MRI characteristics in anaplastic gliomas.2015

    • Author(s)
      Sonoda Y, Shibahara I, Kawaguchi T, Saito R, Kanamori M, Watanabe M, Suzuki H, Kumabe T, Tominaga T
    • Journal Title

      Brain Tumor Pathol

      Volume: in press

    • Related Report
      2014 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Activation of the NRF2 pathway and its impact on the prognosis of anaplastic glioma patients.2015

    • Author(s)
      Kanamori M*, Higa T, Sonoda Y, Murakami S, Dodo M, Kitamura H, Taguchi K, Shibata T, Watanabe M, Suzuki H, Shibahara I, Saito R, Yamashita Y, Kumabe T, Yamamoto M, Motohashi H*, and Tominaga T.
    • Journal Title

      Neuro-Oncology

      Volume: 17 Issue: 4 Pages: 555-565

    • DOI

      10.1093/neuonc/nou282

    • Related Report
      2014 Annual Research Report
    • Peer Reviewed / Open Access / Acknowledgement Compliant
  • [Journal Article] Concentration rather than dose defines the local brain toxicity of agents that are effectively distributed by convection-enhanced delivery.2014

    • Author(s)
      Zhang R, Saito R, Mano Y, Kanamori M, Sonoda Y, Kumabe T, Tominaga T
    • Journal Title

      J Neurosci Methods

      Volume: 222 Pages: 131-137

    • DOI

      10.1016/j.jneumeth.2013.11.004

    • Related Report
      2013 Research-status Report
    • Peer Reviewed
  • [Journal Article] Early response to chemotherapy as an indicator for the management of germinoma-like tumors of the pineal and/or suprasellar regions.2014

    • Author(s)
      Saito R, Kumabe T, Kanamori M, Sonoda Y, Watanabe M, Mugikura S, Takahashi S, Tominaga T
    • Journal Title

      J Clin Neurosci

      Volume: 21 Issue: 1 Pages: 124-130

    • DOI

      10.1016/j.jocn.2013.05.014

    • Related Report
      2013 Research-status Report
    • Peer Reviewed
  • [Presentation] Convection-enhanced delivery of nimustine hydrochloride for brainstem malignant glioma: current study and development of new device.2014

    • Author(s)
      Ryuta Saito
    • Organizer
      20th International Conference on Brain Tumor Research and Therapy
    • Place of Presentation
      Lake Tahoe, California, USA
    • Year and Date
      2014-07-22
    • Related Report
      2014 Annual Research Report
    • Invited
  • [Presentation] 脳腫瘍幹細胞モデルに対する共刺激因子CD40免疫治療の開発2013

    • Author(s)
      長南雅志、齋藤竜太、柴原一陽、金森政之、園田順彦、隈部俊宏、渡辺みか、菊池利明、石井直人、冨永悌二
    • Organizer
      第31回日本脳腫瘍学会学術集会
    • Place of Presentation
      宮崎
    • Related Report
      2013 Research-status Report
  • [Presentation] Convection-enhanced delivery of nimustine hydrochloride for malignant glioma affecting brainstem2013

    • Author(s)
      Ryuta Saito, Yukihiko Sonoda, Teiji Tominaga
    • Organizer
      15th World Congress of Neurosurgery
    • Place of Presentation
      Seoul, Korea
    • Related Report
      2013 Research-status Report
    • Invited

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Published: 2014-07-25   Modified: 2019-07-29  

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