2021 Fiscal Year Final Research Report
Novel therapeutic strategy for brain metastasis of lung cancer using herpes simplex thymidine kinase bearing Muse cells.
| Project/Area Number |
19K09523
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Multi-year Fund |
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| Section | 一般 |
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| Review Section |
Basic Section 56010:Neurosurgery-related
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| Research Institution | Hamamatsu University School of Medicine |
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Principal Investigator |
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| Co-Investigator(Kenkyū-buntansha) |
小泉 慎一郎 浜松医科大学, 医学部附属病院, 講師 (10456577)
難波 宏樹 浜松医科大学, 医学部, 特命研究教授 (60198405)
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| Project Period (FY) |
2019-04-01 – 2022-03-31
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| Keywords | 自殺遺伝子療法 / 歯髄幹細胞 / HSV-TK / 肺癌脳転移 |
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| Outline of Final Research Achievements |
Wild-type HSV-TK was transfected into SHED, cytotoxicity associated with hypermetabolism of thymidine appeared, so we introduced a mutation that makes it less likely to metabolize thymidine. We demonstrated that the HSV-TK gene can be safely transduced into SHED using the modified HSV-TK, and that SHED-TK is sensitive to GCV and has an anti-tumor effect due to the bystander effect. In the treatment model, the increase in tumor luminescence was suppressed as in the co-transplantation model, and the survival period of mice was prolonged. Suicide gene therapy with TK-expressing SHED was also shown to be effective in lung cancer brain metastases.
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| Free Research Field |
脳腫瘍
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| Academic Significance and Societal Importance of the Research Achievements |
肺癌脳転移に対しては手術や定位放射線治療が選択されるが、制御できないこともある。実 際、原発巣がコントロールされている転移性脳腫瘍患者の生存期間中央値は19.7ヶ月と報告されており、脳転移巣に特異性があり、全身性の副作用が限定的な新規治療法が望まれる疾患である。幹細胞を用いた自殺遺伝子療法はprodrugを使用して腫瘍特異的に抗腫瘍効果を示す点で安全性が高い。
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