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Novel treatment strategy targeting neoantigen induced by epigenetic alterations in malignant glioma formation

Research Project

Project/Area Number 19KK0228
Research Category

Fund for the Promotion of Joint International Research (Fostering Joint International Research (B))

Allocation TypeMulti-year Fund
Review Section Medium-sized Section 56:Surgery related to the biological and sensory functions and related fields
Research InstitutionNagoya University

Principal Investigator

Natsume Atsushi  名古屋大学, 未来社会創造機構, 特任教授 (30362255)

Co-Investigator(Kenkyū-buntansha) 大岡 史治  名古屋大学, 医学系研究科, 講師 (10725724)
青木 恒介  名古屋大学, 医学系研究科, 特任助教 (10759773)
平野 雅規  愛知県がんセンター(研究所), 分子腫瘍学分野, 研修生 (40823076)
加藤 彰  名古屋大学, 未来社会創造機構, 研究員 (50793056)
Project Period (FY) 2019-10-07 – 2023-03-31
Project Status Completed (Fiscal Year 2022)
Budget Amount *help
¥18,330,000 (Direct Cost: ¥14,100,000、Indirect Cost: ¥4,230,000)
Fiscal Year 2022: ¥4,420,000 (Direct Cost: ¥3,400,000、Indirect Cost: ¥1,020,000)
Fiscal Year 2021: ¥4,420,000 (Direct Cost: ¥3,400,000、Indirect Cost: ¥1,020,000)
Fiscal Year 2020: ¥4,160,000 (Direct Cost: ¥3,200,000、Indirect Cost: ¥960,000)
Fiscal Year 2019: ¥5,330,000 (Direct Cost: ¥4,100,000、Indirect Cost: ¥1,230,000)
Keywords脳腫瘍 / ネオアンチゲン / 細胞免疫療法 / キメラ抗原受容体T細胞 / ポドプラニン / シングルセル解析 / マウスモデル / 染色体構造異常 / エピゲノム異常 / 悪性脳腫瘍
Outline of Research at the Start

本研究では脳腫瘍のオルガノイドモデルを作成し、詳細な分子解析を行うことで、脳腫瘍の悪性性質に関わるエピゲノム異常とネオアンチゲン形成のクロストークメカニズムの解明を目指す。悪性脳腫瘍の免疫治療研究の第一人者である米国University of California, San Francisco (UCSF) 岡田秀穂教授、脳腫瘍の分子解析研究の第一人者であるカナダ・トロントのLabatt Brain Tumor Research Centre(LBTRC)Michael Taylor 教授との共同研究にてエピゲノム治療と免疫治療を組み合わせた治療法の前臨床研究を目指す。

Outline of Final Research Achievements

We have focused on a molecule named Podoplanin (PDPN) as a therapeutic target of malignant brain tumors. PDPN, a type I transmembrane mucin-like glycoprotein, is abundant in several solid tumors including squamous cell carcinoma, malignant mesothelioma, Kaposi sarcoma, angiosarcoma, testicular seminoma, and brain tumor. The expression level of PDPN is reported to be in accordance with tumor malignancy. We can relieve patients from suffering potential side effects if new measures are developed by which PDPN-expressing tumor cells are only killed.

Academic Significance and Societal Importance of the Research Achievements

本研究により、悪性脳腫瘍の治療にもキメラ抗原受容体(CAR)-T細胞療法が期待できる可能性が明らかになった。マウスの実験では、副作用は確認されず高い安全性が確認されたが、今後の臨床試験での応用を目標に、ヒトへの安全性を十分に検討しなければいけない。また、CAR-T細胞療法とウイルス療法の併用療法がCAR-T細胞療法の効果を強めるという結果が得られたことから、悪性脳腫瘍である膠芽腫の新規治療法が期待される。また、この併用療法の実現に向けて更なる免疫学的メカニズムの解明が必要である。

Report

(5 results)
  • 2022 Annual Research Report   Final Research Report ( PDF )
  • 2021 Research-status Report
  • 2020 Research-status Report
  • 2019 Research-status Report
  • Research Products

    (31 results)

All 2023 2022 2021 2020 2019 Other

All Int'l Joint Research (4 results) Journal Article (18 results) (of which Int'l Joint Research: 5 results,  Peer Reviewed: 17 results,  Open Access: 11 results) Presentation (7 results) (of which Int'l Joint Research: 5 results,  Invited: 5 results) Remarks (2 results)

  • [Int'l Joint Research] Rowan University(米国)

    • Related Report
      2022 Annual Research Report
  • [Int'l Joint Research] Labatt Brain Tumor Research Centre(カナダ)

    • Related Report
      2021 Research-status Report
  • [Int'l Joint Research] UCSF(米国)

    • Related Report
      2019 Research-status Report
  • [Int'l Joint Research] Sick Kids(カナダ)

    • Related Report
      2019 Research-status Report
  • [Journal Article] All-in-One Nanowire Assay System for Capture and Analysis of Extracellular Vesicles from an <i>ex Vivo</i> Brain Tumor Model2023

    • Author(s)
      Chattrairat Kunanon、Yasui Takao、Suzuki Shunsuke、Natsume Atsushi、Nagashima Kazuki、Iida Mikiko、Zhang Min、Shimada Taisuke、Kato Akira、Aoki Kosuke、Ohka Fumiharu、Yamazaki Shintaro、Yanagida Takeshi、Baba Yoshinobu
    • Journal Title

      ACS Nano

      Volume: 17 Issue: 3 Pages: 2235-2244

    • DOI

      10.1021/acsnano.2c08526

    • Related Report
      2022 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Electron-transfer kinetics through nucleic acids untangled by single-molecular fluorescence blinking2022

    • Author(s)
      Fan Shuya、Xu Jie、Osakada Yasuko、Hashimoto Katsunori、Takayama Kazuya、Natsume Atsushi、Hirano Masaki、Maruyama Atsushi、Fujitsuka Mamoru、Kawai Kumi、Kawai Kiyohiko
    • Journal Title

      Chem

      Volume: 8 Issue: 11 Pages: 3109-3119

    • DOI

      10.1016/j.chempr.2022.07.025

    • Related Report
      2022 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] The first-in-human phase I study of a brain-penetrant mutant IDH1 inhibitor DS-1001 in patients with recurrent or progressive IDH1-mutant gliomas2022

    • Author(s)
      Natsume Atsushi、et al.
    • Journal Title

      Neuro-Oncology

      Volume: 25 Issue: 2 Pages: 326-336

    • DOI

      10.1093/neuonc/noac155

    • Related Report
      2022 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Efficacy of cancer-specific anti-podoplanin CAR-T cells and oncolytic herpes virus G47Δ combination therapy against glioblastoma2022

    • Author(s)
      Chalise Lushun、Kato Akira、Ohno Masasuke、Maeda Sachi、Yamamichi Akane、Kuramitsu Shunichiro、Shiina Satoshi、Takahashi Hiromi、Ozone Sachiko、Yamaguchi Junya、Kato Yukinari、Rockenbach Yumi、Natsume Atsushi、Todo Tomoki
    • Journal Title

      Molecular Therapy - Oncolytics

      Volume: 26 Pages: 265-274

    • DOI

      10.1016/j.omto.2022.07.006

    • Related Report
      2022 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Urinary MicroRNA-Based Diagnostic Model for Central Nervous System Tumors Using Nanowire Scaffolds2021

    • Author(s)
      Kitano Yotaro、Aoki Kosuke、Ohka Fumiharu、Yamazaki Shintaro、Motomura Kazuya、Tanahashi Kuniaki、Hirano Masaki、Naganawa Tsuyoshi、Iida Mikiko、Shiraki Yukihiro、Nishikawa Tomohide、Shimizu Hiroyuki、Yamaguchi Junya、Maeda Sachi、Suzuki Hidenori、Wakabayashi Toshihiko、Baba Yoshinobu、Yasui Takao、Natsume Atsushi
    • Journal Title

      ACS Applied Materials & Interfaces

      Volume: 13 Issue: 15 Pages: 17316-17329

    • DOI

      10.1021/acsami.1c01754

    • Related Report
      2021 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Effects of insular resection on interactions between cardiac interoception and emotion recognition.2021

    • Author(s)
      2.Terasawa Y, Motomura K, Natsume A, Iijima K, Chalise L, Sugiura J, Yamamoto H, Koyama K, Wakabayashi T, Umeda S.
    • Journal Title

      Cortex

      Volume: 137 Pages: 271-81

    • Related Report
      2021 Research-status Report
    • Peer Reviewed
  • [Journal Article] Effects of aspirin and heparin treatment on perioperative outcomes in patients with Moyamoya disease.2021

    • Author(s)
      3.Kanamori F, Araki Y, Yokoyama K, Uda K, Mamiya T, Nishihori M, Izumi T, Okamoto S, Natsume A.
    • Journal Title

      Acta Neurochir (Wien)

      Volume: 163 Issue: 5 Pages: 1485-91

    • DOI

      10.1007/s00701-020-04668-0

    • Related Report
      2021 Research-status Report
  • [Journal Article] Mathematical Modeling and Mutational Analysis Reveal Optimal Therapy to Prevent Malignant Transformation in Grade II IDH-Mutant Gliomas.2021

    • Author(s)
      Aoki K, Suzuki H, Yamamoto T, Yamamoto KN, Maeda S, Okuno Y, Ranjit M, Kitano Y, Yamaguchi J, Yamazaki S, Nakamura H, Takahashi M, Narita Y, Nakada M, Deguchi S, Mizoguchi M, Momii Y, Muragaki Y, Abe T, Akimoto J, Wakabayashi T, Saito R, Ogawa S, Haeno H, Natsume A.
    • Journal Title

      Cancer Res.

      Volume: 81 Pages: 4861-4873

    • Related Report
      2021 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Ependymoma-like tumor with mesenchymal differentiation harboring C11orf95-NCOA1/2 or -RELA fusion: A hitherto unclassified tumor related to ependymoma2021

    • Author(s)
      Tomomasa R, Arai Y, Kawabata-Iwakawa R, Fukuoka K, Nakano Y, Hama N, Nakata S, Suzuki N, Ishi Y, Tanaka S, Takahashi JA, Yuba Y, Shiota M, Natsume A, Kurimoto M, Shiba Y, Aoki M, Nabeshima K, Enomoto T, Inoue T, Fujimura J, Kondo A, Yao T, Okura N, Hirose T, Sasaki A, Hirato J, Yokoo H, Nobusawa S.
    • Journal Title

      Brain Pathol .

      Volume: 1 Issue: 3 Pages: 1-9

    • DOI

      10.1111/bpa.12943

    • Related Report
      2020 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Navigated repetitive transcranial magnetic stimulation as preoperative assessment in patients with brain tumors2020

    • Author(s)
      Motomura Kazuya、Takeuchi Hiroki、Nojima Ippei、Aoki Kosuke、Chalise Lushun、Iijima Kentaro、Wakabayashi Toshihiko、Natsume Atsushi
    • Journal Title

      Scientific Reports

      Volume: 10 Issue: 1 Pages: 1-1

    • DOI

      10.1038/s41598-020-65944-8

    • Related Report
      2020 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] H3F3A mutant allele specific imbalance in an aggressive subtype of diffuse midline glioma, H3 K27M-mutant.2020

    • Author(s)
      Maeda S, Ohka F, Okuno Y, Aoki K, Motomura K, Takeuchi K, Kusakari H, Yanagisawa N, Sato S, Yamaguchi J, Tanahashi K, Hirano M, Kato A, Shimizu H, Kitano Y, Yamazaki S, Yamashita S, Takeshima H, Shinjo K, Kondo Y, Wakabayashi T, Natsume A.
    • Journal Title

      Acta Neuropathologica Communications

      Volume: 8 Issue: 1 Pages: 8-19

    • DOI

      10.1186/s40478-020-0882-4

    • Related Report
      2019 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Preoperative predictive factors affecting return to work in patients with gliomas undergoing awake brain mapping.2020

    • Author(s)
      Yoshida A, Motomura K, Natsume A, Chalise L, Iijima K, Hara D, Kadono I, Wakai K, Wakabayashi T.
    • Journal Title

      J Neurooncol.

      Volume: 146(1) Issue: 1 Pages: 195-205

    • DOI

      10.1007/s11060-019-03371-0

    • Related Report
      2019 Research-status Report
    • Peer Reviewed
  • [Journal Article] Trautmann-focused mastoidectomy for a simple, safe presigmoid approach: technical note.2020

    • Author(s)
      Tanahashi K, Uda K, Araki Y, Takeuchi K, Choo J, Chalise L, Motomura K, Ohka F, Wakabayashi T, Natsume A.
    • Journal Title

      J Neurosurg.

      Volume: 3 Issue: 3 Pages: 1-5

    • DOI

      10.3171/2020.1.jns193179

    • Related Report
      2019 Research-status Report
    • Peer Reviewed
  • [Journal Article] Pathogenic Epigenetic Consequences of Genetic Alterations in IDH-Wild-Type Diffuse Astrocytic Gliomas2019

    • Author(s)
      Ohka Fumiharu、Shinjo Keiko、Deguchi Shoichi、Matsui Yusuke et al.
    • Journal Title

      Cancer Research

      Volume: 79 Issue: 19 Pages: 4814-4827

    • DOI

      10.1158/0008-5472.can-19-1272

    • Related Report
      2019 Research-status Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Aberrant Transcriptional Regulation of Super-enhancers by RET Finger Protein-histone Deacetylase 1 Complex in Glioblastoma: Chemoresistance to Temozolomide2019

    • Author(s)
      NATSUME Atsushi、HIRANO Masaki、RANJIT Melissa、AOKI Kosuke、WAKABAYASHI Toshihiko
    • Journal Title

      Neurologia medico-chirurgica

      Volume: 59 Issue: 8 Pages: 293-298

    • DOI

      10.2176/nmc.ra.2019-0049

    • NAID

      130007690186

    • ISSN
      0470-8105, 1349-8029
    • Related Report
      2019 Research-status Report
    • Peer Reviewed
  • [Journal Article] Neurocognitive and functional outcomes in patients with diffuse frontal lower-grade gliomas undergoing intraoperative awake brain mapping.2019

    • Author(s)
      Motomura K, Chalise L, Ohka F, Aoki K, Tanahashi K, Hirano M, Nishikawa T, Yamaguchi J, Shimizu H, Wakabayashi T, Natsume A.
    • Journal Title

      J Neurosurg.

      Volume: 17 Issue: 6 Pages: 1-9

    • DOI

      10.3171/2019.3.jns19211

    • Related Report
      2019 Research-status Report
    • Peer Reviewed
  • [Journal Article] Posterior Cerebral Artery Reconstruction by In-Situ Bypass with Superior Cerebellar Artery via Occipital Transtentorial Approach2019

    • Author(s)
      Tanahashi Kuniaki、Araki Yoshio、Uda Kenji、Muraoka Shinsuke、Motomura Kazuya、Lushun Chalise、Wakabayashi Toshihiko、Natsume Atsushi
    • Journal Title

      World Neurosurgery

      Volume: 126 Pages: 24-29

    • DOI

      10.1016/j.wneu.2019.02.127

    • Related Report
      2019 Research-status Report
    • Peer Reviewed
  • [Journal Article] Aberrant Active cis-Regulatory Elements Associated with Downregulation of RET Finger Protein Overcome Chemoresistance in Glioblastoma2019

    • Author(s)
      Ranjit Melissa、Hirano Masaki、Aoki Kosuke、Okuno Yusuke、Ohka Fumiharu、Yamamichi Akane、Kato Akira、Maeda Sachi、Motomura Kazuya、Matsuo Keitaro、Enomoto Atsushi、Ino Yasushi、Todo Tomoki、Takahashi Masahide、Wakabayashi Toshihiko、Kato Takuya、Natsume Atsushi
    • Journal Title

      Cell Reports

      Volume: 26 Issue: 9 Pages: 2274

    • DOI

      10.1016/j.celrep.2019.01.109

    • Related Report
      2019 Research-status Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Presentation] 脳腫瘍におけるゲノム医療・遺伝子パネル検査2021

    • Author(s)
      夏目敦至
    • Organizer
      第62回日本神経病理学会総会
    • Related Report
      2021 Research-status Report
    • Invited
  • [Presentation] 次現世代における成人脳腫瘍の診断と治療2021

    • Author(s)
      夏目敦至
    • Organizer
      第32回日本脳腫瘍学会学術総会
    • Related Report
      2021 Research-status Report
    • Invited
  • [Presentation] Impact of molecular-genetic crowding on clonal evolution of glioma2021

    • Author(s)
      Atsushi Natsume
    • Organizer
      World Federation of Neuro-Oncology Societies
    • Related Report
      2021 Research-status Report
    • Int'l Joint Research / Invited
  • [Presentation] Molecular and genetic classification of brain tumors2019

    • Author(s)
      Atsushi Natsume
    • Organizer
      The WFNS Educational Course
    • Related Report
      2019 Research-status Report
    • Int'l Joint Research / Invited
  • [Presentation] Brain functional mapping and awake craniotomy for brain tumors2019

    • Author(s)
      Atsushi Natsume
    • Organizer
      The WFNS Educational Course
    • Related Report
      2019 Research-status Report
    • Int'l Joint Research / Invited
  • [Presentation] Phase I study of a brain penetrant mutant IDH1 inhibitor DS-1001b in patients with recurrent or progressive IDH1 mutant gliomas2019

    • Author(s)
      Atsushi Natsume(発表者), Hiroshi Tsubouchi(17人中17番目)
    • Organizer
      ASCO2019
    • Related Report
      2019 Research-status Report
    • Int'l Joint Research
  • [Presentation] Mathematical prediction for precision medicine of CNS glial tumors2019

    • Author(s)
      Kosuke Aoki(17人中1番目), Atsushi Natsume (演者:17人中17番目)
    • Organizer
      11th AACR-JCA Joint Conference on Breakthroughs in Cancer Research: Biology to Precision Medicine
    • Related Report
      2019 Research-status Report
    • Int'l Joint Research
  • [Remarks] PDPN Central

    • URL

      https://pdpn.info

    • Related Report
      2022 Annual Research Report
  • [Remarks] 名古屋大学大学院医学系研究科 脳神経外科 脳腫瘍グループ

    • URL

      https://med-nagoya-neurosurgery.jp/intro/group/group1

    • Related Report
      2019 Research-status Report

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Published: 2019-10-10   Modified: 2024-01-30  

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