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Immunotherapy targeting brain tumor stem cell antigen and niche

Research Project

Project/Area Number 24659657
Research Category

Grant-in-Aid for Challenging Exploratory Research

Allocation TypeMulti-year Fund
Research Field Cerebral neurosurgery
Research InstitutionKeio University

Principal Investigator

TODA Masahiro  慶應義塾大学, 医学部, 准教授 (20217508)

Co-Investigator(Renkei-kenkyūsha) UEDA Ryo  慶應義塾大学, 医学部, 共同研究員 (30317143)
Project Period (FY) 2012-04-01 – 2015-03-31
Project Status Completed (Fiscal Year 2014)
Budget Amount *help
¥3,900,000 (Direct Cost: ¥3,000,000、Indirect Cost: ¥900,000)
Fiscal Year 2014: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000)
Fiscal Year 2013: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000)
Fiscal Year 2012: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Keywords腫瘍幹細胞 / 免疫療法 / 微小環境 / 脳腫瘍幹細胞 / 免疫抑制 / グリオーマ
Outline of Final Research Achievements

In this study, we demonstrated that glioma cells and brain tumor stem cells (BTSCs) expressed highly VEGF (vascular endothelial growth factor) and VEGFR (vascular endothelial growth factor receptor) in vitro. Furthermore, VEGFR was shown to express highly within malignant glioma tissues compared with surrounding brain tissue. In a clinical study, we performed a novel immunotherapy using VEGFR1/VEGFR2 peptides in 8 patients with recurrent malignant glioma and analyzed the cytotoxic T lymphocytes (CTLs) specific to VEGFR1/VEGFR2. After the vaccination with VEGFR1/VEGFR2, CTLs specific to VEGFR1 were induced in 6 out of 6 patients analyzed and CTLs specific to VEGFR2 in 2 out of 6 patients. These results suggest that an immunotherapy using VEGFR1/2 peptides to inhibit the VEGF/VEGFR signal may be effective for the treatment of malignant glioma.

Report

(4 results)
  • 2014 Annual Research Report   Final Research Report ( PDF )
  • 2013 Research-status Report
  • 2012 Research-status Report
  • Research Products

    (43 results)

All 2015 2014 2013 2012 Other

All Journal Article (24 results) (of which Peer Reviewed: 24 results,  Acknowledgement Compliant: 1 results,  Open Access: 2 results) Presentation (17 results) (of which Invited: 4 results) Book (2 results)

  • [Journal Article] Pilocytic astrocytoma with anaplastic features presenting good long-term clinical course after surgery alone: a case report2015

    • Author(s)
      Saito K, Toda M, Yoshida K
    • Journal Title

      Childs Nerv Syst

      Volume: 31 Issue: 1 Pages: 167-171

    • DOI

      10.1007/s00381-014-2509-1

    • Related Report
      2014 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Gruber's ligament as a useful landmark of Abducens nerve in transnasal approach2015

    • Author(s)
      Tomio R, Toda M, Sutiono AB, Horiguchi T, Aiso S, Yoshida K
    • Journal Title

      J Neurosurg

      Volume: 122 Issue: 3 Pages: 499-503

    • DOI

      10.3171/2014.10.jns132437

    • Related Report
      2014 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Various patterns of the middle cerebral vein and preservation of venous drainage during the anterior transpetrosal approach2015

    • Author(s)
      Shibao S, Toda M, Orii M, Fujiwara H, Yoshida K
    • Journal Title

      J Neurosurg

      Volume: なし

    • Related Report
      2014 Annual Research Report
    • Peer Reviewed
  • [Journal Article] GH-producing Pituitary Adenoma and Concomitant Rathke’s Cleft Cyst: A case report and short review2015

    • Author(s)
      Tamura R, Takahashi S, Emoto K, Nagashima H, Toda M, Yoshida K
    • Journal Title

      Case Reports in Neurological Medicine

      Volume: なし

    • Related Report
      2014 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Anterior petrosal approach (Letter to the Editor)2014

    • Author(s)
      Tomio R, Toda M, Yoshida K, Borghei-Razavi H
    • Journal Title

      J Neurosurg

      Volume: 120 Issue: 5 Pages: 1249-1250

    • DOI

      10.3171/2013.10.jns132121

    • Related Report
      2014 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Primary dural closure and anterior cranial base reconstruction using pericranial and nasoseptal multi-layered flaps in endoscopic-assisted skull base surgery2014

    • Author(s)
      Tomio R, Toda M, Tomita T, Yazawa M, Kono M, Ogawa K, Yoshida K
    • Journal Title

      Acta Neurochirurgica

      Volume: なし Issue: 10 Pages: 1911-1915

    • DOI

      10.1007/s00701-014-2174-x

    • Related Report
      2014 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Isolated Pituitary Tuberculoma2014

    • Author(s)
      Saito K, Toda M, Shido S, Tomita T, Ogawa K, Yoshida K
    • Journal Title

      NMC Case Report Journal

      Volume: 1 Issue: 1 Pages: 33-36

    • DOI

      10.2176/nmccrj.2013-0330

    • NAID

      130004648821

    • ISSN
      2188-4226
    • Related Report
      2014 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Analysis of the Bacterial Flora in the Nasal Cavity and the Sphenoid Sinus Mucosa in Patients Operated on with an Endoscopic Endonasal Transsphenoidal Approach2014

    • Author(s)
      Shibao S, Toda M, Tomita T, Ogawa K, Yoshida K
    • Journal Title

      Neurologia medico-chirurgica

      Volume: 54 Issue: 12 Pages: 1009-1013

    • DOI

      10.2176/nmc.oa.2014-0129

    • NAID

      130004704537

    • ISSN
      0470-8105, 1349-8029
    • Related Report
      2014 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Transoral vs. Endoscopic Endonasal Approach for Clival/Upper Cervical Chordoma2014

    • Author(s)
      Shidoh S, Toda M, Kawase T, Nakajima H, Tomita T, Ogawa K, Yoshida K
    • Journal Title

      Neurologia medico-chirurgica

      Volume: 54 Issue: 12 Pages: 991-998

    • DOI

      10.2176/nmc.st.2014-0135

    • NAID

      130004704542

    • ISSN
      0470-8105, 1349-8029
    • Related Report
      2014 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Functional analysis of a novel glioma antigen, EFTUD12014

    • Author(s)
      Saito K, Iizuka Y, Ohta S, Takahashi S, Nakamura K, Saya H, Yoshida K, Kawakami Y, Toda M
    • Journal Title

      Neuro Oncol

      Volume: 16 Issue: 12 Pages: 1618-1629

    • DOI

      10.1093/neuonc/nou132

    • Related Report
      2014 Annual Research Report
    • Peer Reviewed / Acknowledgement Compliant
  • [Journal Article] Petrous apex cholesterol granuloma: importance of pedicled nasoseptal flap in addition to silicone T-tube for prevention of occlusion of drainage route in transsphenoidal approach – a technical note2014

    • Author(s)
      Shibao S, Toda M, Tomita T, Saito K ,Kawase T, Ogawa K, Yoshida K
    • Journal Title

      Neurol Med Chir (Tokyo)

      Volume: なし

    • NAID

      130005065370

    • Related Report
      2014 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Steroid psychosis caused by perioperative steroid replacement for pituitary adenoma: A case report2014

    • Author(s)
      Mizutani K, Toda M, Kikuchi R, Uchida H, Yoshida K
    • Journal Title

      Keio J Med

      Volume: なし

    • NAID

      130005060926

    • Related Report
      2014 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Isolated Pituitary Tuberculoma - Case Reports -2014

    • Author(s)
      Saito K, Toda M, Shido S, Tomita T, Ogawa K, Yoshida K
    • Journal Title

      Neurologia medico-chirurgica

      Volume: -

    • Related Report
      2013 Research-status Report
    • Peer Reviewed
  • [Journal Article] Our experience in anterior petrosal approach. Letter to the editor2014

    • Author(s)
      Tomio R, Borghei-Razavi H, Toda M, Yoshida K
    • Journal Title

      J Neurosurg

      Volume: -

    • Related Report
      2013 Research-status Report
    • Peer Reviewed
  • [Journal Article] Transoral-transpalatal approach and endoscopic endonasal approach for chordomas of the craniovertebral junction2013

    • Author(s)
      Shidoh S, Toda M, Nakajima H, Tomita T, Ogawa K, Kawase T, Yoshida K
    • Journal Title

      J Neurol Neurophysiol

      Volume: 4(4) Issue: 04 Pages: 162-162

    • DOI

      10.4172/2155-9562.1000162

    • Related Report
      2013 Research-status Report
    • Peer Reviewed
  • [Journal Article] Sox6 up-regulation by macrophage migration inhibitory factor promotes survival and maintenance of mouse neural stem/progenitor cells2013

    • Author(s)
      Ohta S, Misawa A, Lefebvre V, Okano H, Kawakami Y, Toda M
    • Journal Title

      PLoS One

      Volume: 8(9) Issue: 9 Pages: e74315-e74315

    • DOI

      10.1371/journal.pone.0074315

    • Related Report
      2013 Research-status Report
    • Peer Reviewed
  • [Journal Article] Glioma Stem Cells and Immunotherapy for the Treatment of Malignant Gliomas2013

    • Author(s)
      Toda M
    • Journal Title

      ISRN Oncology

      Volume: 2013 Pages: 1-13

    • DOI

      10.1155/2013/673793

    • Related Report
      2013 Research-status Report
    • Peer Reviewed
  • [Journal Article] Infratentorial low-grade oligoastrocytoma with aggressive clinical behavior in an adult: a case report with genetic characterization2013

    • Author(s)
      Sano K, Toda M, Sasaki H, Kitamura Y, Mikami S, Hirato J, Inoue S, Kawase T, Yoshida K
    • Journal Title

      Brain Tumor Pathol

      Volume: 30(2) Issue: 2 Pages: 99-103

    • DOI

      10.1007/s10014-012-0111-3

    • Related Report
      2013 Research-status Report
    • Peer Reviewed
  • [Journal Article] Surgical results of an endoscopic endonasal approach for clival chordomas2012

    • Author(s)
      Saito K, Toda M, Tomita T, Ogawa K, Yoshida K
    • Journal Title

      Acta Neurochir (Wien)

      Volume: 154 (5) Issue: 5 Pages: 879-886

    • DOI

      10.1007/s00701-012-1317-1

    • Related Report
      2012 Research-status Report
    • Peer Reviewed
  • [Journal Article] Application of endoscopic transsphenoidal approach to true type transsellar transsphenoidal meningoencephalocele in an adult: A case report and literature review2012

    • Author(s)
      Saito K, Toda M, Tomita T, Sano K, Ogawa K, Yoshida K
    • Journal Title

      Acta Neurochir (Wien)

      Volume: 154 Issue: 8 Pages: 1511-1515

    • DOI

      10.1007/s00701-012-1346-9

    • Related Report
      2012 Research-status Report
    • Peer Reviewed
  • [Journal Article] Epidural anterior petrosectomy with subdural visualization of sphenobasal vein via the anterior transpetrosal approach-technical case report.2012

    • Author(s)
      Ichimura S, Yoshida K, Kagami H, Inaba M, Orii M, Kitamura Y, Saga I, Toda M
    • Journal Title

      Neurosurg Rev

      Volume: 35 Issue: 4 Pages: 609-613

    • DOI

      10.1007/s10143-012-0405-2

    • Related Report
      2012 Research-status Report
    • Peer Reviewed
  • [Journal Article] Macrophage migration inhibitory factor (MIF) promotes cell survival and proliferation of neural stem/progenitor cells2012

    • Author(s)
      Ohta S, Misawa A, Fukaya R, Inoue S,Kanemura Y, Okano H, Kawakami Y, Toda M
    • Journal Title

      J Cell Sci

      Volume: 125 Pages: 3210-3220

    • DOI

      10.1242/jcs.102210

    • Related Report
      2012 Research-status Report
    • Peer Reviewed
  • [Journal Article] Brain Tumor Stem Cells and Immunotherapy2012

    • Author(s)
      Saga I, Toda M
    • Journal Title

      Journal of Cancer Research Updates

      Volume: 1 Issue: 1 Pages: 28-38

    • DOI

      10.6000/1929-2279.2012.01.01.06

    • Related Report
      2012 Research-status Report
    • Peer Reviewed
  • [Journal Article] Infratentorial low-grade oligoastrocytoma with aggressive clinical behavior in an adult: a case report with genetic characterization2012

    • Author(s)
      Sano K, Toda M, Sasaki H, Kitamura Y, Mikami S, Hirato J, Inoue S, Kawase T, Yoshida K
    • Journal Title

      Brain Tumor Pathol

      Volume: -

    • Related Report
      2012 Research-status Report
    • Peer Reviewed
  • [Presentation] ペプチドワクチンの臨床経験2015

    • Author(s)
      戸田正博
    • Organizer
      第10回信濃町脳腫瘍セミナー
    • Place of Presentation
      慶應義塾大学病院新教育研究棟講堂(東京都)
    • Year and Date
      2015-02-07
    • Related Report
      2014 Annual Research Report
    • Invited
  • [Presentation] 悪性神経膠腫に対するVEGFR1/2ワクチン療法2014

    • Author(s)
      柴尾俊輔、戸田正博、菊地亮吾、斉藤克也、植田 良、佐々木光、吉田一成
    • Organizer
      第32回日本脳腫瘍学会学術集会
    • Place of Presentation
      シェラトン・グランデ・トーキョーベイ・ホテル(千葉県)
    • Year and Date
      2014-12-01
    • Related Report
      2014 Annual Research Report
  • [Presentation] 神経膠芽腫における新規標的抗原の発現・機能解析2014

    • Author(s)
      菊地亮吾、戸田正博、斉藤克也、吉田一成
    • Organizer
      日本脳神経外科学会第73回学術総会
    • Place of Presentation
      グランドプリンスホテル新高輪(東京都)
    • Year and Date
      2014-10-09
    • Related Report
      2014 Annual Research Report
  • [Presentation] 脳腫瘍の最新治療2014

    • Author(s)
      戸田正博
    • Organizer
      第19回日本脳腫瘍の外科学会 市民公開講座
    • Place of Presentation
      慶應義塾大学病院3号館北棟1階ラウンジ(東京都)
    • Year and Date
      2014-09-14
    • Related Report
      2014 Annual Research Report
    • Invited
  • [Presentation] Glioblastoma長期生存例の検討2014

    • Author(s)
      中川 佑、佐々木光、戸田正博、大平貴之、河瀬 斌、吉田一成
    • Organizer
      第19回日本脳腫瘍の外科学会
    • Place of Presentation
      東京ドームホテル(東京都)
    • Year and Date
      2014-09-12
    • Related Report
      2014 Annual Research Report
  • [Presentation] 神経膠芽腫における新規標的抗原の発現解析2014

    • Author(s)
      菊地亮吾、戸田正博、斉藤克也、吉田一成
    • Organizer
      第32回日本脳腫瘍病理学会学術集会
    • Place of Presentation
      あわぎんホール(徳島県郷土文化会館)(徳島県)
    • Year and Date
      2014-05-23
    • Related Report
      2014 Annual Research Report
  • [Presentation] 進行及び再発悪性神経膠腫に対するVEGFR1/2ワクチン療法

    • Author(s)
      柴尾俊輔、戸田正博、斉藤克也、植田 良、吉田一成
    • Organizer
      第31回日本脳腫瘍学会学術集会
    • Place of Presentation
      フェニックス・シーガイア・リゾート(宮崎県)
    • Related Report
      2013 Research-status Report
  • [Presentation] Gliomaに対する遺伝子診断に基づくneoadjuvant approach

    • Author(s)
      佐々木光、廣瀬雄一、矢崎貴仁、片山 真、北村洋平、戸田正博、大平貴之、吉田一成
    • Organizer
      第18回日本脳腫瘍の外科学会
    • Place of Presentation
      大津プリンスホテル
    • Related Report
      2013 Research-status Report
  • [Presentation] 脳腫瘍幹細胞抗原の解析と新たな免疫療法の臨床試験

    • Author(s)
      戸田正博
    • Organizer
      第46回慶應ニューロサイエンス研究会
    • Place of Presentation
      慶應義塾大学医学部新教育研究棟講堂3(東京都)
    • Related Report
      2013 Research-status Report
    • Invited
  • [Presentation] Pilocytic astrocytoma with anaplastic (atypical) features の一例

    • Author(s)
      斉藤克也、戸田正博、木村徳宏、池田栄二、吉田一成
    • Organizer
      第31回日本脳腫瘍病理学会
    • Place of Presentation
      KFC Hall 国際ファッションセンター(東京都)
    • Related Report
      2013 Research-status Report
  • [Presentation] Moleclar-guided neoadjuvant approach for gliomas regardless of histology

    • Author(s)
      Sasaki H, Hirose Y, Katayama M, Yazaki T, Toda M, Ohira T, Yoshida K
    • Organizer
      第4回国際脳腫瘍病理シンポジウム
    • Place of Presentation
      名古屋国際会議場 (名古屋)
    • Related Report
      2012 Research-status Report
  • [Presentation] Molecular-guided neoadjuvant aproach for gliomas

    • Author(s)
      Sasaki H, Hirose Y, Katayama M, Yazaki T, Toda M, Ohira T, Yoshida K
    • Organizer
      The 19th International Brain Tumor Research and Therapy Conference
    • Place of Presentation
      Niagara Falls (Cnada)
    • Related Report
      2012 Research-status Report
  • [Presentation] Low-grade gliomaに対する遺伝子診断に基づくneoadjuvant approach

    • Author(s)
      佐々木光、廣瀬雄一、片山 真、 矢崎貴仁、北村洋平、戸田正博、大平貴之、吉田一成
    • Organizer
      日本脳神経外科学会第71回学術総会
    • Place of Presentation
      大阪国際会議場 (大阪)
    • Related Report
      2012 Research-status Report
  • [Presentation] 遺伝学的解析に基づいた神経膠腫の治療戦略 指定発言

    • Author(s)
      戸田正博
    • Organizer
      第24回脳神経外科臨床講座
    • Place of Presentation
      ベルサール八重洲 (東京)
    • Related Report
      2012 Research-status Report
    • Invited
  • [Presentation] 進行・再発悪性グリオーマに対するVEGFRワクチンの第1/2相臨床試験

    • Author(s)
      戸田 正博、斉藤克也、植田 良、佐々木光、吉田一成
    • Organizer
      第30回日本脳腫瘍学会学術集会
    • Place of Presentation
      グランドプリンスホテル広島 (広島)
    • Related Report
      2012 Research-status Report
  • [Presentation] リボソーム合成阻害を介した治療標的分子としてのグリオーマ新規抗原EFTUD1の解析

    • Author(s)
      斉藤克也、戸田正博、吉田一成
    • Organizer
      第30回日本脳腫瘍学会学術集会
    • Place of Presentation
      グランドプリンスホテル広島 (広島)
    • Related Report
      2012 Research-status Report
  • [Presentation] 再発悪性グリオーマに対するペプチドワクチン

    • Author(s)
      戸田正博
    • Organizer
      第9回信濃町脳腫瘍セミナー
    • Place of Presentation
      慶應義塾大学医学部 新教育研究棟 (東京)
    • Related Report
      2012 Research-status Report
  • [Book] 先端医療シリーズ45        臨床医のための最新脳神経外科2014

    • Author(s)
      戸田正博
    • Total Pages
      628
    • Publisher
      寺田国際事務所/先端医療技術研究所
    • Related Report
      2014 Annual Research Report
  • [Book] Glioma: Immunotherapeutic approaches2012

    • Author(s)
      Toda M
    • Total Pages
      232
    • Publisher
      In Landes Bioscience
    • Related Report
      2012 Research-status Report

URL: 

Published: 2013-05-31   Modified: 2019-07-29  

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