Development of new treatment for brain tumor stem cells
| Project/Area Number |
17K16661
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| Research Category |
Grant-in-Aid for Young Scientists (B)
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| Allocation Type | Multi-year Fund |
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| Research Field |
Neurosurgery
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| Research Institution | Keio University |
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Principal Investigator |
Kikuchi Ryogo 慶應義塾大学, 医学部(信濃町), 共同研究員 (10594723)
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| Project Period (FY) |
2017-04-01 – 2019-03-31
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| Project Status |
Completed (Fiscal Year 2018)
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| Budget Amount *help |
¥4,160,000 (Direct Cost: ¥3,200,000、Indirect Cost: ¥960,000)
Fiscal Year 2018: ¥2,080,000 (Direct Cost: ¥1,600,000、Indirect Cost: ¥480,000)
Fiscal Year 2017: ¥2,080,000 (Direct Cost: ¥1,600,000、Indirect Cost: ¥480,000)
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| Keywords | 脳腫瘍幹細胞 / ペプチドワクチン / DEPDC1 / PD-1抗体 / ワクチン療法 / 脳腫瘍学 / 免疫療法 |
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| Outline of Final Research Achievements |
DEPDC1 knockdown prolonged overall survival and increased apoptosis / necrosis cells. Immunohistochemical staining showed that CD4 or CD8 positive lymphocytes proliferated around the tumor, suggesting that suppression of DEPDC1 might inhibit tumor immune tolerance.
Treatment experiments were conducted in brain tumor mouse model using GL261. The combined therapy of the peptide vaccine and the PD-1 antibody confirmed suppression of tumor growth and prolongation of survival time. Analysis using immunohistochemical staining suggested that PD-1 antibody combination may increase T cell infiltration.
Our data suggested potential of clinical application using peptide vaccine.
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| Academic Significance and Societal Importance of the Research Achievements |
悪性脳腫瘍の代表格である膠芽腫の標準治療は、最大限の手術摘出と、引き続くtemozolomideを用いた化学療法と放射線療法を組み合わせた集学的療法であるが、近年でもその生存予後は1.5年程度と過去数十年間ほとんど改善していない。特に術前画像・術中所見にて判別できない正常脳への腫瘍細胞の浸潤が問題で、腫瘍特異的に作用する新たな分子標的療法の開発が望まれる。本研究では腫瘍幹細胞の発現する腫瘍抗原DEPDC1と、標的分子に対するペプチドワクチンに着目し、DEPDC1を用いたペプチドワクチンの臨床応用に向け基礎研究を行なった。
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Report
(3 results)
Research Products
(3 results)
