2018 Fiscal Year Final Research Report
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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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 |
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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Free Research Field |
悪性脳腫瘍、小児中枢神経系腫瘍、腫瘍幹細胞、免疫療法、腫瘍血管新生
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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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