Development of Novel Vaccine Immunotherapy for Malignant Glioma
| Project/Area Number |
17H04306
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| Research Category |
Grant-in-Aid for Scientific Research (B)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
Neurosurgery
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| Research Institution | Keio University |
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Principal Investigator |
Toda Masahiro 慶應義塾大学, 医学部(信濃町), 准教授 (20217508)
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| Project Period (FY) |
2017-04-01 – 2020-03-31
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| Project Status |
Completed (Fiscal Year 2019)
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| Budget Amount *help |
¥17,030,000 (Direct Cost: ¥13,100,000、Indirect Cost: ¥3,930,000)
Fiscal Year 2019: ¥5,330,000 (Direct Cost: ¥4,100,000、Indirect Cost: ¥1,230,000)
Fiscal Year 2018: ¥5,330,000 (Direct Cost: ¥4,100,000、Indirect Cost: ¥1,230,000)
Fiscal Year 2017: ¥6,370,000 (Direct Cost: ¥4,900,000、Indirect Cost: ¥1,470,000)
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| Keywords | 悪性神経膠腫 / 免疫チェックポイント / PD-1 / VEGFR / ネオアンチゲン / 免疫療法 / 脳腫瘍学 / ワクチン / 腫瘍抗原 / 腫瘍免疫 |
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| Outline of Final Research Achievements |
In the present study, we established a novel combinational immunotherapy using epitope peptide targeting glioma neoantigen and vascular endothelial growth factor receptor (VEGFR)1/2, and anti-programmed cell death (PD)-1. Induced cytotoxic T lymphocytes could kill not only tumor vessel cells but also tumor cells and immunosuppressive regulatory T cells (Tregs) expressing VEGFRs. Remarkable prolonged survival was achieved in the glioma mouse model. Furthermore, we revealed that VEGFR2 is highly expressed in the glioma stem cells (GSCs). This approach could inhibit the proliferation of GSCs in an orthotopic mouse model. The histopathological findings of pre- and post-VEGFRs vaccination glioblastoma specimens demonstrated that more apoptosis was detected in tumor cells, and the number of Foxp3-positive cells decreased after vaccination.
This novel immunotherapy targeting a large variety of cells has the possibility to show higher treatment efficacy for the patients with malignant glioma.
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| Academic Significance and Societal Importance of the Research Achievements |
グリオーマ細胞におけるNeoantigenを標的とするエピトープペプチドと抗PD-1抗体を組み合わせた複合免疫療法に、さらにVEGFR1/VEGFR2を標的とするエピトープペプチドを上乗せすることで、腫瘍細胞のみならず、腫瘍血管内皮細胞や免疫抑制性の制御性T細胞といった腫瘍関連微小環境をも統合的に標的可能であった。さらにBTSCには特にVEGFR2が高発現するため、BTSCを標的とする治療にも応用可能であった。腫瘍の増大には、腫瘍細胞のみならず周囲微小環境が重要な役割を果たすため、本複合免疫療法は新たな治療戦略となり得る。
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Report
(4 results)
Research Products
(27 results)
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[Journal Article] Clinical and histopathological analyses of VEGF receptors peptide vaccine in patients with primary glioblastoma - a case series.2020
Author(s)
Tamura R, Morimoto Y, Kosugi K, Sato M, Oishi Y, Ueda R, Kikuchi R, Nagashima H, Noji S, Kawakami Y, Sasaki H, Yoshida K, Toda M.
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Journal Title
BMC Cancer.
Volume: Apr 14;20(1)
Issue: 1
Pages: 301-301
DOI
Related Report
Peer Reviewed / Open Access
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[Journal Article] A VEGF receptor vaccine demonstrates preliminary efficacy in neurofibromatosis type 2.2019
Author(s)
Tamura Ryota, Fujioka Masato, Morimoto Yukina, Ohara Kentaro, Kosugi Kenzo, Oishi Yumiko, Sato Mizuto, Ueda Ryo, Fujiwara Hirokazu, Noji Shinobu, Oishi Naoki, Ogawa Kaoru, Kawakami Yutaka, Ohira Takayuki, Yoshida Kazunari, Toda Masahiro.
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Journal Title
Nature Communications
Volume: 10
Issue: 1
Pages: 5758-5768
DOI
Related Report
Peer Reviewed
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[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
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Journal Title
Related Report
Peer Reviewed / Open Access
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[Patent(Industrial Property Rights)] 癌治療用キット2020
Inventor(s)
戸田正博、森本佑紀奈、田村亮太、河上裕、谷口智憲
Industrial Property Rights Holder
戸田正博、森本佑紀奈、田村亮太、河上裕、谷口智憲
Industrial Property Rights Type
特許
Industrial Property Number
2020-002439
Filing Date
2020
Related Report
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