2015 Fiscal Year Final Research Report
Augmentation of tumor specificity and killing activity of oncolytic herpes virus vectors
| Project/Area Number |
25290059
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| Research Category |
Grant-in-Aid for Scientific Research (B)
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| Allocation Type | Partial Multi-year Fund |
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| Section | 一般 |
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| Research Field |
Tumor therapeutics
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| Research Institution | The University of Tokyo (2014-2015)
Tokyo University of Pharmacy and Life Science (2013) |
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Principal Investigator |
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| Co-Investigator(Kenkyū-buntansha) |
YAMAGUCHI MIKI 札幌医科大学, 医学部, 助教 (10530454)
FUKUHARA TAKESHI 東京薬科大学, 生命科学部, 助教 (20359673)
TAHARA HIDEAKI 東京大学, 医科学研究所, 教授 (70322071)
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| Project Period (FY) |
2013-04-01 – 2016-03-31
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| Keywords | 遺伝子治療 / 腫瘍溶解性ウイルス療法 / ヘルペスウイルス / 抗体 / がん |
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| Outline of Final Research Achievements |
We previously reported a retargeted herpes simplex virus (HSV) platform that incorporates single-chain antibodies (scFv) into gD to mediate entry solely via cancer antigens. In this study, we introduced syncytial mutations, known to confer hyperactivity in cell-cell fusion, into our retargeted HSVs, and found that the mutations enabled extensive formation of syncytia and enhanced killing activity on human tumor lines that express the target molecules. Furthermore, we took advantage of our collection of monoclonal antibodies selected for targeting activity as components of gene delivery vectors. We derived an scFv from a hybridoma clone that produces an anti-epithelial cell adhesion molecule (EpCAM) antibody, and inserted it into our retargeted platform, and found that the virus showed EpCAM-dependent virus entry and spread. Our strategies may be useful to develop a widely applicable oncolytic HSV platform that confers powerful oncolytic activity and stringent tumor selectivity.
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| Free Research Field |
遺伝子治療
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