Development of immuno-gene therapy strategy using co-stimulatorymolecule linking local treatment and systemic anti-tumor effect.

• Project/Area Number: 23791583
• Research Category: Grant-in-Aid for Young Scientists (B)
• Allocation Type: Multi-year Fund
• Research Field: Cerebral neurosurgery
• Research Institution: Tohoku University
• Principal Investigator: SAITO Ryuta 東北大学, 大学院・医学系研究科, 助教 (10400243)
• Project Period (FY): 2011 – 2012
• Project Status: Completed (Fiscal Year 2012)
• Budget Amount: ¥4,290,000 (Direct Cost: ¥3,300,000、Indirect Cost: ¥990,000); Fiscal Year 2012: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000); Fiscal Year 2011: ¥2,470,000 (Direct Cost: ¥1,900,000、Indirect Cost: ¥570,000)
• Keywords: 中枢神経系薬剤送達 / 腫瘍ワクチン / 脳腫瘍 / 化学療法 / 免疫治療 / 共刺激因子 / 薬剤送達 / 局所治療 / OX40

Research Abstract

In this study, we confirmed that co-stimulatory molecule OX-40 plays pivotal role in inducing strong anti-tumor efficacy. Using OX-40 agonistic antibody, immunostimulatory effect was evaluated. Induction of anti-tumor effect was strongest when OX-40 signal was activated together with subcutaneous tumor vaccination. Thus, we tried to develop new immunotherapeutic strategy against glioblastoma. Activation of OX-40 signaling can be promising immunotherapy for glioblastoma.

Research Products

• [Journal Article] Computational simulation of convection enhanced drug delivery in the non-human primate brainstem: a simple model predicting the drug distribution (2013)
  • Author(s): Sugiyama S,Saito R, 他8名
  • Journal Title: Neurol Res Volume: (In press) Issue: 8 Pages: 773-781
  • DOI: 10.1179/1743132813y.0000000215
  • Peer Reviewed
• [Journal Article] グリオーマ治療におけるConvection-enhanced Delivery (2013)
  • Author(s): 齋藤竜太、冨永悌二
  • Journal Title: 癌と化学療法 Volume: 40(6)(in press)
• [Journal Article] The expression status of CD133 is associated with the pattern and timing of primary glioblastoma recurrence (2013)
  • Author(s): Shibahara I, Sonoda Y, Saito R, 他8名
  • Journal Title: Neuro Oncol
  • Peer Reviewed
• [Journal Article] Pilomyxoid astrocytoma of the cerebellum with Williams syndrome (2013)
  • Author(s): Chonan M, Kanamori M, Kumabe T, Saito R, 他2名
  • Journal Title: Childs Nerv Syst
  • Peer Reviewed
• [Journal Article] Infarction of the lateral posterior choroidal artery territory after manipulation of the choroid plexus at the atrium: causal association with subependymal artery injury (2013)
  • Author(s): Saito R, 他6名
  • Journal Title: J Neurosurg
  • Peer Reviewed
• [Journal Article] Dynamic changes in magnetic resonance imaging appearance of dysembryoplastic neuroepithelial tumor with or without malignant transformation (2013)
  • Author(s): Mano Y,Kumabe T,Shibahara I, Saito R, 他3名
  • Journal Title: J Neurosurg Pediatr Volume: 11(5) Issue: 5 Pages: 518-525
  • DOI: 10.3171/2013.1.peds11449
  • Peer Reviewed
• [Journal Article] Malignant pediatric brain tumor of primitive small round cell proliferation withbland-looking mesenchymal spindle cell elements (2013)
  • Author(s): Ito A,Kumabe T,Saito R, 他4名
  • Journal Title: Brain Tumor Pathol Volume: 30(2) Issue: 2 Pages: 109-116
  • DOI: 10.1007/s10014-012-0106-0
  • Peer Reviewed
• [Journal Article] Clinicopathological analysis of nine consecutive central nervous systemprimitive neuroectodermal tumors in a single institute (2013)
  • Author(s): Aizawa-Kohama M,Kumabe T,Saito R, 他5名
  • Journal Title: Brain Tumor Pathol Volume: 30(1) Issue: 1 Pages: 15-27
  • DOI: 10.1007/s10014-012-0097-x
  • Peer Reviewed
• [Journal Article] Metachronous, multicentric glioma of pilocytic astrocytoma with oligodendroglioma-like component and oligodendroglioma through distinct genetic aberrations (2013)
  • Author(s): Kanoke A,Kanamori M,Kumabe T,Saito R, 他2名
  • Journal Title: J Neurosurg Volume: 118(4) Issue: 4 Pages: 854-858
  • DOI: 10.3171/2012.9.jns112353
  • Peer Reviewed
• [Journal Article] Medial posterior choroidal artery territory infarction associated with tumor removal in the pineal/tectum/thalamus region through the occipital transtentorial approach. (2013)
  • Author(s): aito R, Kumabe T, Kanamori M, Sonoda Y, Mugikura S, Takahashi S, Tominaga T.
  • Journal Title: Clin Neurol Neurosurg. Volume: 印刷中 Issue: 8 Pages: 1257-1263
  • DOI: 10.1016/j.clineuro.2012.11.020
  • Peer Reviewed
• [Journal Article] Infarction of the lateral posterior choroidal artery territory after manipulation of the choroid plexus at the atrium: causal association with subependymal artery injury. (2013)
  • Author(s): Saito R, Kumabe T, Sonoda Y, Kanamori M, Mugikura S, Takahashi S, Tominaga T.
  • Journal Title: J Neurosurg. Volume: in press
  • Peer Reviewed
• [Journal Article] グリオーマ治療におけるコンベクションエンハンストデリバリー (2013)
  • Author(s): 齋藤竜太、冨永悌二
  • Journal Title: 癌と化学療法 Volume: 40
• [Journal Article] Clinical and histological characteristics of recurrent oligodendroglial tumors: comparison between primary and recurrent tumors in 18 cases (2012)
  • Author(s): Kanamori M, Kumabe T,Shibahara I,Saito R, 他5名
  • Journal Title: Brain Tumor Pathol
  • Peer Reviewed
• [Journal Article] Convection-enhanced delivery: from mechanisms to clinical drug delivery fordiseases of the central nervous system (2012)
  • Author(s): Saito R,Tominaga T
  • Journal Title: Neurol Med Chir (Tokyo) Volume: 52(8) Pages: 531-538
  • NAID: 10030694427
  • Peer Reviewed
• [Journal Article] Safety and feasibility of convection-enhanced delivery of nimustine hydrochloride co-infused with free gadolinium for real-time monitoring in the primate brain. (2012)
  • Author(s): Sugiyama S、ほか８名
  • Journal Title: Neurol Res Volume: 34 Issue: 6 Pages: 581-7
  • DOI: 10.1179/1743132812y.0000000050
  • Peer Reviewed
• [Journal Article] IDH1/2 gene status defines the prognosis and molecular profiles in patients with grade III gliomas. (2012)
  • Author(s): Shibahara I、ほか10名
  • Journal Title: Int J Clin Oncol Volume: 17 Issue: 6 Pages: 551-61
  • DOI: 10.1007/s10147-011-0323-2
  • Peer Reviewed
• [Journal Article] Convection-Enhanced Delivery: From Mechanisms to Clinical Drug Delivery for Diseases of the Central Nervous System (2012)
  • Author(s): Saito R, Tominaga T
  • Journal Title: Neurologia medico-chirurgica Volume: 52 Issue: 8 Pages: 531-538
  • DOI: 10.2176/nmc.52.531
  • NAID: 10030694427
  • ISSN: 0470-8105, 1349-8029
  • Peer Reviewed
• [Journal Article] Local convection-enhanced delivery of chemotherapeutic agent transiently opens blood-brain barrier and improves efficacy of systemic chemotherapy in intracranial xenograft tumor model (2011)
  • Author(s): Nakamura T, Saito R, Sugiyama S, Sonoda Y, Kumabe T, Tominaga T
  • Journal Title: Cancer Letter Volume: 310 Issue: 1 Pages: 77-83
  • DOI: 10.1016/j.canlet.2011.06.018
  • Peer Reviewed
• [Journal Article] Regression of recurrent glioblastoma infiltrating the brainstem after convection-enhanced delivery of nimustine hydrochloride (2011)
  • Author(s): Saito R, Sonoda Y, Kumabe T, Nagamatsu K, Watanabe M, Tominaga T
  • Journal Title: J Neurosurg Pediatr Volume: 7 Issue: 5 Pages: 522-526
  • DOI: 10.3171/2011.2.peds10407
  • Peer Reviewed
• [Journal Article] Preoperative evaluation of the deep cerebral veins using 3-tesla magnetic resonance imaging (2011)
  • Author(s): Saito R, Kumabe T, Kanamori M, Yamashita Y, Sonoda Y, Higano S, Takahashi S, Tominaga T
  • Journal Title: Minim Invasive Neurosurg Volume: 54 Issue: 03 Pages: 105-109
  • DOI: 10.1055/s-0031-1279715
  • Peer Reviewed
• [Journal Article] Combination chemotherapy with ifosfamide, cisplatin, and etoposide for medulloblastoma : single-institute experience and differences in efficacy for subgroups of medulloblastoma (2011)
  • Author(s): Saito R, Kumabe T, Sonoda Y, Kanamori M, Yamashita Y, Watanabe M, Tominaga T
  • Journal Title: Childs Nerv Syst Volume: 27 Issue: 9 Pages: 1399-1406
  • DOI: 10.1007/s00381-011-1485-y
  • Peer Reviewed
• [Presentation] 脳幹部再発神経膠腫に対するMRIガイド下CEDによる塩酸ニムスチン投与 (2012)
  • Author(s): 齋藤竜太, 他5名
  • Organizer: 第30回日本脳腫瘍学会学術集会
  • Place of Presentation: 広島
• [Presentation] Convection-enhanced delivery of nimustine hydrochloride (ACNU) for recurrent glioma patients (2012)
  • Author(s): Saito R, 他5名
  • Organizer: 2012Society for Neurooncology Annual Meeting
  • Place of Presentation: Washington DC, USA
• [Presentation] 再発神経膠腫に対するコンベクション・エンハンスト・デリバリー:Update (2012)
  • Author(s): 齋藤竜太, 他5名
  • Organizer: 第71回日本脳神経外科学術総会
  • Place of Presentation: 大阪
• [Presentation] Convection-enhanced Delivery of ACNU (2012)
  • Author(s): Saito R, 他5名
  • Organizer: Second InternationalMeeting of the Society for CNS Interstitial Delivery of Therapeutics
  • Place of Presentation: Chicago USA
• [Presentation] 抗癌剤分子性質による局所投薬時の脳局所毒性発現パターンの違いに関する研究 (2012)
  • Author(s): 齋藤竜太, 他6名
  • Organizer: 第13回日本分子脳神経外科学会
  • Place of Presentation: 熊本
• [Presentation] Surgery for Thalamic Glioma (2012)
  • Author(s): Saito R, 他5名
  • Organizer: 第17回日本脳腫瘍の外科学会
  • Place of Presentation: 横浜
• [Presentation] 毛様性星細胞腫のMRI所見と病理 (2012)
  • Author(s): 齋藤竜太、略
  • Organizer: 第30回日本脳腫瘍病理学会学術集会
  • Place of Presentation: 名古屋
• [Presentation] 膠芽腫における共刺激シグナルOX40の相反する役割及び免疫治療への応用 (2012)
  • Author(s): 柴原一陽、齋藤竜太
  • Organizer: 第71回日本脳神経外科学会学術総会
  • Place of Presentation: 大阪国際会議場
• [Presentation] 膠芽腫における共刺激シグナルOX40の相反する役割及び免疫治療への応用 (2012)
  • Author(s): 柴原一陽、齋藤竜太
  • Organizer: 第30回日本脳腫瘍学会
  • Place of Presentation: グランドプリンスホテル広島
• [Presentation] 膠芽腫における共刺激シグナルOX40の相反する役割及び免疫治療への応用 (2012)
  • Author(s): 柴原一陽、齋藤竜太
  • Organizer: 第13回日本分子脳神経外科学会
  • Place of Presentation: 熊本市国際交流会館
• [Presentation] CED of ACNU (2012)
  • Author(s): Ryuta Saito
  • Organizer: Second International Meeting of the Society for CNS Interstital Delivery of Therapeutics
  • Place of Presentation: 米国、シカゴ
  • Invited
• [Presentation] 再発神経膠腫に対するコンベクション エンハンスト デリバリー：Up date (2012)
  • Author(s): 齋藤竜太
  • Organizer: 第71回日本脳神経外科学会学術総会
  • Place of Presentation: 大阪国際会議場
• [Presentation] Local Application of Chemotherapeutics Transiently Opens Blood-Brain Barrier and Improves Efficacy of Systemic Chemotherapy against Intracranial Xenograft Tumor Model (2011)
  • Author(s): Saito R, 他4名
  • Organizer: 2011Society forNeurooncology Annual Meeting
  • Place of Presentation: Orange County USA
• [Presentation] 脳腫瘍への有効な薬剤送達技術:コンベクション・エンハンスト・デリバリー (2011)
  • Author(s): 齋藤竜太, 他3名
  • Organizer: 第29回日本脳腫瘍学会学術集会
  • Place of Presentation: 岐阜
• [Presentation] MRIモニタリング下ニトロソウレア剤局所投薬による悪性神経膠腫新規治療法の開発 (2011)
  • Author(s): 齋藤竜太, 他6名
  • Organizer: 第49回日本癌治療学会学術集会
  • Place of Presentation: 名古屋
• [Presentation] 悪性神経膠腫に対するConvection-enhanced delivery:現状と展望 (2011)
  • Author(s): 齋藤竜太, 他5名
  • Organizer: 第70回日本脳神経外科学術総会
  • Place of Presentation: 横浜
• [Presentation] 側脳室三角部近傍の腫瘍摘出における虚血性合併症に関して:脈絡叢障害による外側後脈絡動脈梗塞 (2011)
  • Author(s): 齋藤竜太, 他6名
  • Organizer: 第16回日本脳腫瘍の外科学会
  • Place of Presentation: 横浜
• [Presentation] MRI Guided Convection-Enhanced Delivery of Nimustine Hydrochloride Against Recurrent Glioma Affecting Brain Stem (2011)
  • Author(s): Saito R, 他5名
  • Organizer: 8th Annual WorldCongress of IBMISPS on Brain, Spinal Cord Mapping and Image Guided Therapy
  • Place of Presentation: San Francisco, USA
• [Presentation] Infratentorial oligodendroglial tumor4例の臨床病理学的検討 (2011)
  • Author(s): 齋藤竜太, 他8名
  • Organizer: 第29回日本脳腫瘍病理学会学術集会
  • Place of Presentation: 東京
• [Presentation] Convection-enhanced Delivery:現状と展望 (2011)
  • Author(s): 齋藤竜太, 他3名
  • Organizer: 第31回日本脳神経外科コングレス総会
  • Place of Presentation: 横浜
• [Presentation] MRI Guided Convection-Enhanced Delivery of Nimustine Hydrochloride Against Recurrent Glioma Affecting Brain Stem (2011)
  • Author(s): Ryuta Saito, Yukihiko Sonoda, Yoji Yamashita, Masayuki Kanamori, Toshihiro Kumabe, Teiji Tominaga
  • Organizer: 8th Annual World Congress of IBMISPS on Brain, Spinal Cord Mapping and Image Guided Therapy
  • Place of Presentation: San Francisco, USA
• [Presentation] Convection-enhanced Delivery ： 現状と展望 (2011)
  • Author(s): 齋藤竜太, 園田順彦, 隈部俊宏, 冨永悌二
  • Organizer: 第31回日本脳神経外科コングレス総会(招待講演)
  • Place of Presentation: 横浜
• [Presentation] 悪性神経膠腫に対するConvection-enhanced delivery：現状と展望 (2011)
  • Author(s): 齋藤竜太、園田順彦、山下洋二、金森政之、隈部俊宏、冨永悌二
  • Organizer: 第70回日本脳神経外科学術総会
  • Place of Presentation: 横浜
• [Presentation] MRI モニタリング下ニトロソウレア剤局所投薬による悪性神経膠腫新規治療法の開発 (2011)
  • Author(s): 齋藤竜太、園田順彦、山下洋二、金森政之、永松謙一、隈部俊宏、冨永悌二
  • Organizer: 第49回日本癌治療学会学術集会
  • Place of Presentation: 名古屋
• [Presentation] 脳腫瘍への有効な薬剤送達技術：コンベクション・エンハンスト・デリバリー (2011)
  • Author(s): 齋藤竜太、園田順彦、隈部俊宏、冨永悌二
  • Organizer: 第29回日本脳腫瘍学会学術集会
  • Place of Presentation: 下呂
• [Presentation] Safety and feasibility of MRI guided convection-enhanced delivery of nimustine hydrochloride against recurrent glioma affecting brainstem. (2011)
  • Author(s): Ryuta Saito, Yukihiko Sonoda, Yoji Yamashita, Masayuki Kanamori, Toshihiro Kumabe, Teiji Tominaga
  • Organizer: 16th annual meeting, Society for Neuro-Oncology
  • Place of Presentation: Orange County, USA