Translational research for cancer immunotherapy targeting glioblastoma initiating cells based on WT1 vaccination
Project/Area Number |
15K10331
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Research Category |
Grant-in-Aid for Scientific Research (C)
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Allocation Type | Multi-year Fund |
Section | 一般 |
Research Field |
Neurosurgery
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Research Institution | Osaka University |
Principal Investigator |
Kagawa Naoki 大阪大学, 医学系研究科, 講師 (50444542)
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Co-Investigator(Kenkyū-buntansha) |
保仙 直毅 大阪大学, 医学系研究科, 寄附講座准教授 (10456923)
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Project Period (FY) |
2015-04-01 – 2019-03-31
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Project Status |
Completed (Fiscal Year 2018)
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Budget Amount *help |
¥4,810,000 (Direct Cost: ¥3,700,000、Indirect Cost: ¥1,110,000)
Fiscal Year 2017: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Fiscal Year 2016: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
Fiscal Year 2015: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
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Keywords | 腫瘍幹細胞 / 悪性神経膠腫 / 免疫逃避現象 / 分子標的治療 / 腫瘍血管正常化 / 免疫逃避 / WT1 / ALCAM / 腫瘍免疫 / 免疫療法 |
Outline of Final Research Achievements |
We established research technique using animal model to study resistance to current therapies and immune escape phenomenon of cancer initiating cells in malignant gliomas. We can estimate effects of cancer immunotherapies in vivo by mouse glioma model. Histopathological and molecular cytologic study showed high expression of WT1 protein in glioblastoma initiating cells and higher expression of TGF-b, lower level of CD4-positive T lymphocyte and decreased expression in tumor samples of HLA class I in recurrent cases. Cancer immunotherapy combined with tumor vessel normalization factor induced lymphocyte distribution in glioblastomas and enhanced tumor suppressive effects in glioblastoma models. On based on these new findings, WT1 vaccination combined with molecular targeting therapies (immune check point inhibitors or tumor vessel normalization factors) can overcome immune escape phenomenon of cancer initiating cells and contribute to better clinical outcome for glioblastomas.
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Academic Significance and Societal Importance of the Research Achievements |
悪性神経膠腫は放射線治療や化学療法が奏功しにくい腫瘍であり、免疫療法や分子標的治療、それらの複合的治療を含めたカスタムメイドな治療戦略が、患者にとって福音をもたらす可能性がある。生体での免疫療法効果判定が可能なマウスグリオーマモデルの確立は、悪性神経膠腫の治療開発にとって重要な役割を有すると考えられる。この研究を基に、悪性神経膠腫幹細胞の治療抵抗性の解明とともに免疫逃避機構の一端を明らかにできる可能性が示唆される。また、我々が開発してきたWT1免疫療法に加えて、免疫チェックポイント阻害剤、TGFβ阻害剤、血管正常化因子などを組み合わせることにより、難治性の悪性神経膠腫の治療改善に貢献できる。
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Report
(5 results)
Research Products
(58 results)
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[Journal Article] A phase I clinical study of a cocktail vaccine of Wilms’ tumor 1 (WT1) HLA class I and II peptides for recurrent malignant glioma2018
Author(s)
Tsuboi A, Hashimoto N, Fujiki F, Morimoto S, Kagawa N, Nakajima H, Hosen N, Nishida S, Nakata J, Morita S, Sakamoto J, Oji Y, Oka Y, Sugiyama H
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Journal Title
Cancer Immunology, Immunotherapy
Volume: 68(2)
Issue: 2
Pages: 331-340
DOI
Related Report
Peer Reviewed / Open Access
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[Journal Article] 11C-methionine-18F-FDG dual-PET-tracer-based target delineation of malignant glioma: evaluation of its geometrical and clinical features for planning radiation therapy.2018
Author(s)
Hirata T, Kinoshita M, Tamari, Seo Y, Suzuki O, Wakai N, Achiha T, Umehara T, Arita H, Kagawa N, Kanemura Y, Shimosegawa E, Hashimoto N, Hatazawa J, Kishima H, Teshima T, Ogawa K.
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Journal Title
Journal of Neurosurgery
Volume: 21
Issue: 3
Pages: 1-11
DOI
Related Report
Peer Reviewed / Open Access
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[Journal Article] Diagnostic and Prognostic Value of 11C-Methionine PET for Nonenhancing Gliomas.2016
Author(s)
Takano K, Kinoshita M, Arita H, Okita Y, Chiba Y, Kagawa N, Fujimoto Y, Kishima H, Kanemura Y, Nonaka M, Nakajima S, Shimosegawa E, Hatazawa J, Hashimoto N, Yoshimine T.
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Journal Title
AJNR Am J Neuroradiol
Volume: 37
Issue: 1
Pages: 44-50
DOI
Related Report
Peer Reviewed / Open Access
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[Journal Article] A combination of TERT promoter mutation and MGMT methylation status predicts clinically relevant subgroups of newly diagnosed glioblastomas.2016
Author(s)
Arita H, Yamasaki K, Matsushita Y, Nakamura T, Shimokawa A, Takami H, Tanaka S, Mukasa A, Shirahata M, Shimizu S, Suzuki K, Saito K, Kobayashi K, Higuchi F, Uzuka T, Otani R, Tamura K, Sumita K, Ohno M, Miyakita Y, Kagawa N, Hashimoto N, Hatae R, Yoshimoto K, Shinojima N, Nakamura H, Kanemura Y, Okita Y, et al.
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Journal Title
Acta Neuropathol Commun.
Volume: 4
Issue: 1
Pages: 79-79
DOI
Related Report
Peer Reviewed / Open Access
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[Journal Article] Association of WT1 IgG antibody against WT1 peptide with prolonged survival in glioblastoma multiforme patients vaccinated with WT1 peptide.2016
Author(s)
Oji Y, Hashimoto N, Tsuboi A, Murakami Y, Iwai M, Kagawa N, Chiba Y, Izumoto S, Elisseeva O, Ichinohasama R, Sakamoto J, Morita S, Nakajima H, Takashima S, Nakae Y, Nakata J, Kawakami M, Nishida S, Hosen N, Fujiki F, Morimoto S, Adachi M, Iwamoto M, Oka Y, Yoshimine T, Sugiyama H.
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Journal Title
Int J Cancer.
Volume: 139
Issue: 6
Pages: 1391-401
DOI
Related Report
Peer Reviewed / Open Access
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[Journal Article] Introduction of High Throughput Magnetic Resonance T2-Weighted Image Texture Analysis for WHO Grade 2 and 3 Gliomas.2016
Author(s)
Kinoshita M, Sakai M, Arita H, Shofuda T, Chiba Y, Kagawa N, Watanabe Y, Hashimoto N, Fujimoto Y, Yoshimine T, Nakanishi K, Kanemura Y.
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Journal Title
PLoS One
Volume: 11
Issue: 10
Pages: e0164268-e0164268
DOI
Related Report
Peer Reviewed / Open Access
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[Journal Article] Comparison of diffusion tensor imaging and 11C-methionine positron emission tomography for reliable prediction of tumor cell density in gliomas.2016
Author(s)
Kinoshita M, Arita H, Okita Y, Kagawa N, Kishima H, Hashimoto N, Tanaka H, Watanabe Y, Shimosegawa E, Hatazawa J, Fujimoto Y, Yoshimine T
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Journal Title
J Neurosurg
Volume: 印刷中
Issue: 5
Pages: 1136-1142
DOI
Related Report
Peer Reviewed / Open Access / Int'l Joint Research
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[Journal Article] Prognostic value of medulloblastoma extent of resection after accounting for molecular subgroup: a retrospective integrated clinical and molecular analysis.2016
Author(s)
Thompson EM, Hielscher T, Bouffet E, Remke M, Luu B, Kagawa N, Hashimoto N, Jabado N, Shih DJ, Kijima N, Northcott PA, Kool M, Jones DT, Chan JA, Hawkins CE, Tabori U, Drake J, Kulkarni A, Dirks P, Rutka JT, Korshunov A, Pfister SM, Packer RJ, Ramaswamy V, Taylor MD.
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Journal Title
Lancet Oncol.
Volume: 17(4)
Issue: 4
Pages: 484-495
DOI
Related Report
Peer Reviewed / Open Access / Int'l Joint Research
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[Journal Article] Association of WT1 IgG antibody against WT1 peptide with prolonged survival in glioblastoma multiforme patients vaccinated with WT1 peptide.2016
Author(s)
Oji Y, Naoya Hashimoto N, Tsuboi A, Murakami Y, Iwai M, Kagawa N, Chiba Y, Izumoto S, Eliseeva O, Ichinohasama R, Sakamoto J, Morita S, Nakajima H, Takashima S, Nakae Y, Nakata J, Kawakami M, Nishida S, Hosen N, Fujiki F, Morimoto S, Adachi M, Iwamoto M, Oka Y, Yoshimine T, Sugiyama H.
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Journal Title
Related Report
Peer Reviewed / Open Access
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[Journal Article] Comparison of diffusion tensor imaging and 11C-methionine positron emission tomography for reliable prediction of tumor cell density in gliomas.2016
Author(s)
Kinoshita M, Arita H, Okita Y, Kagawa N, Kishima H, Hashimoto N, Tanaka H, Watanabe Y, Shimosegawa E, Hatazawa J, Fujimoto Y, Yoshimine T.
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Journal Title
J Neurosurg.
Volume: -
Pages: 1-7
Related Report
Peer Reviewed / Open Access
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[Journal Article] Diagnostic and Prognostic Value of 11C-Methionine PET for Nonenhancing Gliomas.2016
Author(s)
Takano K, Kinoshita M, Arita H, Okita Y, Chiba Y, Kagawa N, Fujimoto Y, Kishima H, Kanemura Y, Nonaka M, Nakajima S, Shimosegawa E, Hatazawa J, Hashimoto N, Yoshimine T.
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Journal Title
AJNR Am J Neuroradiol.
Volume: 37(1)
Pages: 44-50
Related Report
Peer Reviewed / Open Access
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[Journal Article] Wilms tumor 1 peptide vaccination combined with temozolomide against newly diagnosed glioblastoma: safety and impact on immunological response2015
Author(s)
Naoya Hashimoto, Akihiro Tsuboi, Naoki Kagawa, Yasuyoshi Chiba, Shuichi Izumoto, Manabu Kinoshita, Noriyuki Kijima, Yoshihiro Oka, Soyoko Morimoto, Hiroko Nakajima, Satoshi Morita, Junichi Sakamoto, Sumiyuki Nishida, Naoki Hosen, Yusuke Oji, Norio Arita, Toshiki Yoshimine, Haruo Sugiyama
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Journal Title
Cancer Immunology Immunotherapy
Volume: -
Issue: 6
Pages: 707-16
DOI
Related Report
Peer Reviewed / Open Access / Acknowledgement Compliant
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[Journal Article] 3.Treatment outcomes using CyberKnife for brain metastases from lung cancer.2014
Author(s)
Tamari K, Suzuki O, Hashimoto N, Kagawa N, Fujiwara M, Sumida I, Seo Y , Isohashi F, Yoshioka Y, Yoshimine T, Ogawa K.
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Journal Title
J Radiat Res
Volume: -
Issue: 1
Pages: 151-8
DOI
Related Report
Peer Reviewed / Open Access / Acknowledgement Compliant
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[Presentation] Immunotherapy for malignant glioma in children: WT1 peptide vaccination and future direction2018
Author(s)
Naoki Kagawa, Yoshiko Hashii, Syogo Fukuya, Takamune Achiha, Chisato Yokota, Takanori Fukunaga, Daisuke Eino, Hideyuki Arita, Yasuyoshi Chiba, Yasunori Fujimoto, Naoya Hashimoto, Haruo Sugiyama, Haruhiko Kishima
Organizer
The 46th Annual Meeting of the International Society for Pediatric Neurosurgery
Related Report
Int'l Joint Research
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[Presentation] Therapeutic strategies and problems for radiation-induced intracranial tumors after irradiation for pediatric cancers2018
Author(s)
Naoki Kagawa, Chisato Yokota, Toru Umehara, Takamune Achiha, Takanori Fukunaga, Daisuke Eino, Shogo Fukuya, Yasuyoshi Chiba, Hideyuki Arita, Yasunori Fujimoto, Haruhiko Kishima
Organizer
The 46th Annual Meeting of the International Society for Pediatric Neurosurgery
Related Report
Int'l Joint Research
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[Presentation] Diagnostic exposure to low-dose radiation and spontaneous regression in intracranial germ cell tumors2018
Author(s)
Naoki Kagawa, Ryuichi Hirayama, Shogo Fukuya, Chisato Yokota, Yasunori Fujimoto, Yasuyoshi Chiba, Daisuke Eino, Toru Umehara, Takanori Fukunaga, Manabu Kinoshita, Haruhiko Kishima
Organizer
The 18th International Symposium on Pediatric Neuro-Oncology
Related Report
Int'l Joint Research
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[Presentation] Hypersensitivity of intracranial germinomas for low-dose radiation: relationship between diagnostic radiation dose and volumetric changes before chemoradiotherapy2016
Author(s)
Kagawa N, Hirayama R, Fujimoto Y, Chiba Y, Yokota C, Fukuya S, Eino D, Takano K, Kinoshita M, Hashimoto N, Yoshimine Y
Organizer
The 17th International Symposium on Pediatric Neuro-Oncology
Place of Presentation
Liverpool(UK)
Year and Date
2016-06-13
Related Report
Int'l Joint Research
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[Presentation] 再発小児悪性神経膠腫に対するWT1ペプチドワクチン療法2016
Author(s)
香川尚己, 橋井佳子, 橋本 直哉, 平山龍一, 千葉泰良, 有田英之, 藤本康倫,坪井昭博, 尾路祐介, 岡芳弘, 杉山治夫, 吉峰俊樹
Organizer
一般社団法人日本脳神経外科学会第75回学術総会
Place of Presentation
福岡
Related Report
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[Presentation] 再発小児悪性神経膠腫に対するWT1ペプチドワクチン療法の有効性と問題点2016
Author(s)
香川尚己, 橋井佳子, 橋本 直哉, 平山龍一, 千葉泰良, 有田英之, 藤本康倫,坪井昭博, 尾路祐介, 岡芳弘, 杉山治夫, 吉峰俊樹
Organizer
第34回日本脳腫瘍学会学術集会
Place of Presentation
山梨
Related Report
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