2020 Fiscal Year Final Research Report
Novel treatment for neuroblastoma by using live-attenuated poliovirus
Project/Area Number |
18K07817
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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 |
Review Section |
Basic Section 52050:Embryonic medicine and pediatrics-related
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Research Institution | Mie University |
Principal Investigator |
Toyoda Hidemi 三重大学, 医学系研究科, 准教授 (60525327)
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Project Period (FY) |
2018-04-01 – 2021-03-31
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Keywords | 神経芽腫 / ポリオウイルス |
Outline of Final Research Achievements |
We have demonstrated that neuroblastoma (NB) subcutaneously implanted in immuno-competent mice is eliminated by intratumoral administration of poliovirus (PV). Our results also suggested that the in vivo destruction of NB cells by virotherapy lead to a robust antitumor immune response. Since we used CD155-transfected NB for experiments, CD155 might be a target for antitumor immune response. Although NB can grow in naive mice, no tumor growth was observed in mice cured of NB that were reinnoculated with NB cells. Splenocytes harvested from NB-bearing mice treated with PV exhibited higher lytic activity against NB cells than did those from splenocytes derived from naive mice. In vitro T-cell depletion experiments indicated that CD8+ T cells were essential for the cytotoxic antitumor activity of splenocytes.
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Free Research Field |
小児血液腫瘍
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Academic Significance and Societal Importance of the Research Achievements |
ポリオウイルスに感染した腫瘍細胞が抗腫瘍免疫を誘導することを証明できれば、ポリオウイルスで細胞死を誘導した腫瘍細胞を将来がんワクチンとして使用できる可能性も広がります。さらにマイクロアレイを用いて抗腫瘍免疫誘導の原因遺伝子が同定できれば、その遺伝子のコードするタンパクをがんワクチンの抗原として使用することも可能になり、またCAR-T療法の応用につながります。さらに、ポリオウイルスは神経芽腫だけでなく脳腫瘍を初めとする他の固形腫瘍にも細胞死を誘導することが知られているため、神経芽腫の治療だけでなく脳腫瘍など他の難治性小児がんの治療への臨床応用が可能な研究成果です。
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