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Gene-cell therapy using iPS cells for the treatment of brain tumor

Research Project

Project/Area Number 16K15648
Research Category

Grant-in-Aid for Challenging Exploratory Research

Allocation TypeMulti-year Fund
Research Field Neurosurgery
Research InstitutionKeio University

Principal Investigator

TODA MASAHIRO  慶應義塾大学, 医学部(信濃町), 准教授 (20217508)

Co-Investigator(Renkei-kenkyūsha) MINE Yutaka  慶應義塾大学, 医学部, 訪問研究員 (10306730)
Project Period (FY) 2016-04-01 – 2018-03-31
Project Status Completed (Fiscal Year 2017)
Budget Amount *help
¥3,380,000 (Direct Cost: ¥2,600,000、Indirect Cost: ¥780,000)
Fiscal Year 2017: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
Fiscal Year 2016: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
Keywords脳腫瘍学 / ゲノム編集 / 幹細胞 / 自殺遺伝子
Outline of Final Research Achievements

In this study, the HSV-tK gene was firstly transduced into neural stem cells (NSCs) differentiated from human iPS cells using a viral vector. HSV-tk expressing iPS-NSCs were transplanted into human brain tumor model mice, and the effectiveness of this therapy by administration of ganciclovir (GCV) was demonstrated. Next, HSV-tk gene was introduced into iPS by genome editing, but HSV-tk expressing iPS cell line could not be established due to cytotoxicity. Then, Tet-inducible HSV-tk transduced iPS cells were established using gene expression induction system. After induction of differentiation into therapeutic NSCs, these NSCs were transplanted into brain tumor model mice. After administration of GCV with Doxycycline, a remarkable therapeutic effect of this therapy using gene expression induction system was confirmed.

Report

(3 results)
  • 2017 Annual Research Report   Final Research Report ( PDF )
  • 2016 Research-status Report
  • Research Products

    (31 results)

All 2018 2017 2016

All Journal Article (14 results) (of which Peer Reviewed: 13 results,  Open Access: 12 results) Presentation (12 results) (of which Int'l Joint Research: 3 results,  Invited: 5 results) Book (2 results) Patent(Industrial Property Rights) (3 results)

  • [Journal Article] An Analysis of Various Tracts of Mastoid Air Cells Related to Cerebrospinal Fluid Leak after the Anterior Transpetrosal Approach.2018

    • Author(s)
      Tamura R, Tomio R, Mohammad F, Toda M, Yoshida K.
    • Journal Title

      J Neurosurg.

      Volume: -

    • Related Report
      2017 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Histopathological vascular investigation of the peritumoral brain zone of glioblastomas.2018

    • Author(s)
      Tamura R, Ohara K, Sasaki H, Morimoto Y, Yoshida K, Toda M.
    • Journal Title

      J Neurooncol.

      Volume: 136 Issue: 2 Pages: 233-241

    • DOI

      10.1007/s11060-017-2648-9

    • Related Report
      2017 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] The analysis of the cerebral venous blood volume in cavernous sinus using 320 row multi-detector CT.2018

    • Author(s)
      Mizutania K, Toda M, Yajima Y, Akiyama T, Fujiwara H, Yoshida K, Jinzaki M
    • Journal Title

      Clin Neurol Neurosurg

      Volume: 167 Pages: 11-16

    • DOI

      10.1016/j.clineuro.2018.02.007

    • Related Report
      2017 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Intraosseous venous structures adjacent to the jugular tubercle associated with an anterior condylar dural arteriovenous fistula.2018

    • Author(s)
      Mizutani T, Akiyama T, Minami Y, Toda M, Fujiwara H, Jinzaki M, Yoshida K
    • Journal Title

      Neuroradiology

      Volume: 60 Issue: 5 Pages: 487-496

    • DOI

      10.1007/s00234-018-1990-8

    • Related Report
      2017 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Stem cell-based therapies for neurological disorders2018

    • Author(s)
      Tamura R, Toda M
    • Journal Title

      AIMS Cell and Tissue Engineering

      Volume: 2 Pages: 24-47

    • Related Report
      2017 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] A pilot study of peptide vaccines for VEGF receptor 1 and 2 in patients with recurrent/progressive high grade glioma2018

    • Author(s)
      Shibao S, Ueda R, Saito K, Kikuchi R, Nagashima H, Kojima A, Kagami H, Sasaki H, Noji S, Kawakami Y, Yoshida K, Toda M
    • Journal Title

      Oncotarget

      Volume: -

    • Related Report
      2017 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Clinical and molecular prognostic factors for long-term survival of the patients with glioblastomas in a single institutional consecutive cohort.2017

    • Author(s)
      Nakagawa Y, Sasaki H, Ohara K, Ezaki T, Toda M, Ohira T, Kawase T, Yoshida K.
    • Journal Title

      World Neurosurg.

      Volume: 106 Pages: 165-173

    • DOI

      10.1016/j.wneu.2017.06.126

    • Related Report
      2017 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Surgical Outcome of Endoscopic Endonasal Surgery for Non-Functional Pituitary Adenoma by a Team of Neurosurgeons and Otolaryngologists Adenoma by a Team of Neurosurgeons and Otolaryngologists.2017

    • Author(s)
      Kikuchi R, Toda M, Tomita T, Ogawa K, Yoshida K.
    • Journal Title

      Turkish Neurosurg.

      Volume: 27 Pages: 1-7

    • DOI

      10.5137/1019-5149.jtn.14354-15.0

    • Related Report
      2017 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Vascularized middle turbinate flap for the endoscopic endonasal reconstruction of the anterior olfactory groove.2016

    • Author(s)
      Tamura R, Toda M, Kohno M, Watanabe Y, Ozawa H, Tomita T, Ogawa K, Yoshida K.
    • Journal Title

      Neurosurg Rev

      Volume: 39(2) Issue: 2 Pages: 297-302

    • DOI

      10.1007/s10143-015-0688-1

    • Related Report
      2016 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] The analysis of the petrosal vein to prevent venous complications during the anterior transpetrosal approach in the resection of petroclival meningioma2016

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

      World Neurosurg.

      Volume: 93 Pages: 175-182

    • DOI

      10.1016/j.wneu.2016.06.018

    • Related Report
      2016 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Analysis of the medial opticocarotid recess in patients with pituitary macroadenoma using three-dimensional images.2016

    • Author(s)
      Kikuchi R, Toda M, Wakahara S, Fujiwara H, Jinzaki M, Yoshida K
    • Journal Title

      World Neurosurg.

      Volume: 93 Pages: 139-143

    • DOI

      10.1016/j.wneu.2016.05.094

    • Related Report
      2016 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Endonasal endoscopic approach for a giant cavernous sinus meningioma that extended to the middle cranial fossa with preoperative embolization2016

    • Author(s)
      Tamura R, Toda M, Kohno M, Ozawa H, Tomita T, Akiyama T, Ogawa K, Yoshida K
    • Journal Title

      Interdisciplinary Neurosurgery

      Volume: 6 Pages: 20-22

    • DOI

      10.1016/j.inat.2016.05.006

    • Related Report
      2016 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] 脳腫瘍の手術のための術前・術中支援 (1)トルコ鞍、斜台近傍腫瘍に対する経鼻内視鏡手術2016

    • Author(s)
      戸田正博
    • Journal Title

      No Shinkei Geka

      Volume: 44 Pages: 975-987

    • Related Report
      2016 Research-status Report
  • [Journal Article] Transvenous Embolization of the Basilar Plexus Before Endoscopic Transsphenoidal Transclival Surgery.2016

    • Author(s)
      Mizutani K, Akiyama T, Toda M, Kanazawa T, Kamamoto D, Yoshida K
    • Journal Title

      World Neurosurg.

      Volume: S1878-8750 Pages: 31010-31015

    • DOI

      10.1016/j.wneu.2016.10.022

    • Related Report
      2016 Research-status Report
    • Peer Reviewed / Open Access
  • [Presentation] 悪性脳腫瘍および神経線維腫症2型に対するワクチン療法2017

    • Author(s)
      戸田 正博
    • Organizer
      第12回信濃町脳腫瘍セミナー
    • Place of Presentation
      慶應義塾大学病院(東京都新宿区)
    • Year and Date
      2017-01-14
    • Related Report
      2016 Research-status Report
  • [Presentation] Endoscopic endonasal approach for the treatment of parasellar lesions2017

    • Author(s)
      戸田正博
    • Organizer
      8th World Congress of Neuroendoscopy
    • Related Report
      2017 Annual Research Report
    • Int'l Joint Research / Invited
  • [Presentation] 神経線維腫症2型に対するVEGFR1/2ペプチドワクチンの臨床試験2017

    • Author(s)
      戸田正博、田村亮太、大平貴之、吉田一成
    • Organizer
      第26回日本聴神経腫瘍研究会
    • Related Report
      2017 Annual Research Report
  • [Presentation] 下垂体-傍鞍部腫瘍2017

    • Author(s)
      戸田正博
    • Organizer
      第22回日本脳腫瘍の外科学会
    • Related Report
      2017 Annual Research Report
    • Invited
  • [Presentation] 悪性神経膠腫に対するヒトiPS細胞を用いた自殺遺伝子細胞療法2017

    • Author(s)
      田村亮太、戸田正博、三好浩之、岩澤千鶴、峯 裕、森本佑紀奈、Sampetrean Oltea、佐谷秀行、岡野栄之、吉田一成
    • Organizer
      第35回日本脳腫瘍学会学術集会
    • Related Report
      2017 Annual Research Report
  • [Presentation] 神経線維腫症2型に対するVEGFRペプチドワクチンの臨床試験2017

    • Author(s)
      戸田正博、田村亮太、大平貴之、吉田一成
    • Organizer
      第35回日本脳腫瘍学会学術集会
    • Related Report
      2017 Annual Research Report
  • [Presentation] 再発悪性神経膠腫に対するカクテルペプチドワクチン療法第1/2相臨床試験2016

    • Author(s)
      菊地亮吾、戸田正博、田村亮太、長島秀明、柴尾俊輔、齋藤克也、植田良、佐々木光、吉田一成
    • Organizer
      第34回日本脳腫瘍学会学術集会
    • Place of Presentation
      甲府富士屋ホテル(山梨県甲府市)
    • Year and Date
      2016-12-05
    • Related Report
      2016 Research-status Report
  • [Presentation] Glioma組織におけるMIFの免疫組織学的発現解析2016

    • Author(s)
      深谷雷太、大多茂樹、谷口智憲、松崎有未、杉原英志、岡野栄之、佐谷秀行、河上裕、河瀬斌、吉田一成、戸田正博
    • Organizer
      第34回日本脳腫瘍学会学術集会
    • Place of Presentation
      甲府富士屋ホテル(山梨県甲府市)
    • Year and Date
      2016-12-05
    • Related Report
      2016 Research-status Report
  • [Presentation] Endoscopic endonasal skull base surgery2016

    • Author(s)
      戸田 正博
    • Organizer
      World Skull Base 2016
    • Place of Presentation
      大阪国際会議場(大阪府大阪市)
    • Year and Date
      2016-06-17
    • Related Report
      2016 Research-status Report
    • Int'l Joint Research / Invited
  • [Presentation] Recent trends Hemostasis in Skull Base Surgery (in Japan)2016

    • Author(s)
      戸田 正博
    • Organizer
      World Skull Base 2016
    • Place of Presentation
      大阪国際会議場(大阪府大阪市)
    • Year and Date
      2016-06-16
    • Related Report
      2016 Research-status Report
    • Int'l Joint Research / Invited
  • [Presentation] 腫瘍血管を標的とした脳腫瘍治療 -新たな免疫療法と手術アプローチの工夫について-2016

    • Author(s)
      戸田 正博
    • Organizer
      第34回日本脳腫瘍病理学会 ランチョンセミナー5
    • Place of Presentation
      東京コンファレンスセンター・有明(東京都江東区)
    • Year and Date
      2016-05-28
    • Related Report
      2016 Research-status Report
    • Invited
  • [Presentation] Subtemporal approach2016

    • Author(s)
      戸田 正博
    • Organizer
      第36回日本脳神経外科コングレス総会
    • Place of Presentation
      大阪国際会議場(大阪府大阪市)
    • Year and Date
      2016-05-19
    • Related Report
      2016 Research-status Report
  • [Book] Brain Tumor-Stem cell research for the treatment of malignant glioma.-2018

    • Author(s)
      Toda M, Tamura R
    • Total Pages
      10
    • Publisher
      InTech
    • Related Report
      2017 Annual Research Report
  • [Book] Annual Review 神経 2017 3.脳腫瘍  1脳腫瘍の免疫療法2017

    • Author(s)
      戸田正博
    • Publisher
      中外医学社
    • Related Report
      2016 Research-status Report
  • [Patent(Industrial Property Rights)] 神経線維腫症ⅠⅠ型患者に発生する腫瘍に対するペプチドワクチン及びペプチドワクチン組成物2017

    • Inventor(s)
      戸田正博、田村亮太
    • Industrial Property Rights Holder
      慶應義塾
    • Industrial Property Rights Type
      特許
    • Filing Date
      2017
    • Related Report
      2017 Annual Research Report
  • [Patent(Industrial Property Rights)] 脳腫瘍治療用細胞製剤2017

    • Inventor(s)
      戸田正博、岡野栄之、三好浩之、田村亮太
    • Industrial Property Rights Holder
      慶應義塾
    • Industrial Property Rights Type
      特許
    • Filing Date
      2017
    • Related Report
      2017 Annual Research Report
  • [Patent(Industrial Property Rights)] iPS細胞を用いた自殺遺伝子脳腫瘍治療薬2017

    • Inventor(s)
      戸田正博、岡野栄之、三好浩之、田村亮太
    • Industrial Property Rights Holder
      慶應義塾
    • Industrial Property Rights Type
      特許
    • Filing Date
      2017
    • Related Report
      2017 Annual Research Report

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Published: 2016-04-21   Modified: 2019-03-29  

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