Augmentation of tumor specificity and killing activity of oncolytic herpes virus vectors
Project/Area Number |
25290059
|
Research Category |
Grant-in-Aid for Scientific Research (B)
|
Allocation Type | Partial Multi-year Fund |
Section | 一般 |
Research Field |
Tumor therapeutics
|
Research Institution | The University of Tokyo (2014-2015) Tokyo University of Pharmacy and Life Science (2013) |
Principal Investigator |
|
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)
|
Project Period (FY) |
2013-04-01 – 2016-03-31
|
Project Status |
Completed (Fiscal Year 2015)
|
Budget Amount *help |
¥17,030,000 (Direct Cost: ¥13,100,000、Indirect Cost: ¥3,930,000)
Fiscal Year 2015: ¥5,330,000 (Direct Cost: ¥4,100,000、Indirect Cost: ¥1,230,000)
Fiscal Year 2014: ¥5,720,000 (Direct Cost: ¥4,400,000、Indirect Cost: ¥1,320,000)
Fiscal Year 2013: ¥5,980,000 (Direct Cost: ¥4,600,000、Indirect Cost: ¥1,380,000)
|
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 / 腫瘍溶解ウイルス療法 |
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.
|
Report
(4 results)
Research Products
(26 results)
-
-
[Journal Article] Development of an oncolytic HSV vector fully retargeted specifically to cellular EpCAM for virus entry and cell-to-cell spread.2016
Author(s)
Shibata T, Uchida H, Shiroyama T, Okubo Y, Suzuki T, Ikeda H, Yamaguchi M, Miyagawa Y, Fukuhara T, Cohen JB, Glorioso JC, Watabe T, Hamada H, Tahara H.
-
Journal Title
Gene Therapy.
Volume: 印刷中
Issue: 6
Pages: 479-488
DOI
Related Report
Peer Reviewed / Int'l Joint Research / Acknowledgement Compliant
-
-
-
[Journal Article] Herpes simplex viral-vector design for efficient transduction of nonneuronal cells without cytotoxicity.2015
Author(s)
Miyagawa Y, Marino P, Verlengia G, Uchida H, Goins WF, Yokota S, Geller DA, Yoshida O, Mester J, Cohen JB, Glorioso JC.
-
Journal Title
Proceedings of the National Academy of Sciences of the United States of America.
Volume: 112
Issue: 13
DOI
Related Report
Peer Reviewed
-
[Journal Article] Use of miRNA response sequences to block off-target replication and increase the safety of an unattenuated, glioblastoma-targeted oncolytic HSV.2015
Author(s)
Mazzacurati L, Marzulli M, Reinhart B, Miyagawa Y, Uchida H, Goins WF, Li A, Kaur B, Caligiuri M, Cripe T, Chiocca N, Amankulor N, Cohen JB, Glorioso JC, Grandi P.
-
Journal Title
Molecular Therapy.
Volume: 23
Issue: 1
Pages: 99-107
DOI
Related Report
Peer Reviewed
-
-
-
-
[Journal Article] Expression of HSV-1 receptors in EBV-associated lymphoproliferative disease determines susceptibility to oncolytic HSV.2013
Author(s)
Wang PY, Currier MA, Hansford L, Kaplan D, Chiocca EA, Uchida H, Goins WF, Cohen JB, Glorioso JC, Kuppevelt TH, Mo X, Cripe TP.
-
Journal Title
Gene Therapy
Volume: 20
Issue: 7
Pages: 761-769
DOI
Related Report
Peer Reviewed
-
[Journal Article] Effective treatment of an orthotopic xenograft model of human glioblastoma using an EGFR-retargeted oncolytic herpes simplex virus.2013
Author(s)
Uchida H, Marzulli M, Nakano K, Goins WF, Chan J, Hong CS, Mazzacurati L, Yoo JY, Haseley A, Nakashima H, Baek H, Kwon H, Kumagai I, Kuroki M, Kaur B, Chiocca EA, Grandi P, Cohen JB, Glorioso JC.
-
Journal Title
Molecular Therapy
Volume: 21
Issue: 3
Pages: 561-569
DOI
Related Report
Peer Reviewed
-
-
-
[Presentation] 腫瘍細胞表面抗原を介して侵入する標的化単純ヘルペスウイルスベクターの開発2015
Author(s)
城山智貴, 内田宏昭, 大久保優, 柴田智子, 福原武志, 山口美樹, Justus B. Cohen, Joseph C. Glorioso, 渡部徹郎, 濱田洋文, 田原秀晃
Organizer
第7回血液疾患免疫療法研究会
Place of Presentation
東京大学本郷キャンパス(東京都文京区)
Year and Date
2015-09-26
Related Report
-
-
-
[Presentation] Development of a new generation of herpes simplex virus vectors fully retargeted to a variety of tumor-associated antigens.2014
Author(s)
Uchida H, Okubo Y, Shibata T, Suzuki T, Ikeda H, Shiroyama T, Fukuhara T, Kojima M, Yamaguchi M, Miyagawa Y, Cohen JB, Glorioso JC, Hamada H.
Organizer
The 20th Annual Meeting of Japan Society of Gene Therapy.
Place of Presentation
東京慈恵会医科大学(東京都港区)
Year and Date
2014-08-06 – 2014-08-08
Related Report
-
-
[Presentation] Generation of an EpCAM-retargeted HSV vector by application of in-house monoclonal antibody resources.2014
Author(s)
Shibata T, Shiroyama T, Suzuki T, Okubo Y, Fukuhara T, Yamaguchi M, Miyagawa Y, Cohen JB, Glorioso JC, Hamada H, Watabe T, Uchida H.
Organizer
The 39th International Herpesvirus Workshop.
Place of Presentation
神戸コンベンションセンター(兵庫県神戸市)
Year and Date
2014-07-19 – 2014-07-23
Related Report
-
[Presentation] Augmentation of oncolytic potential of a fully retargeted HSV vector by introduction of syncytial mutations.2014
Author(s)
Wakata A, Okubo Y, Fukuhara T, Cohen JB, Glorioso JC, Nakano K, Kumagai I, Kuroki M, Hamada H, Watabe T, Uchida H.
Organizer
The 39th International Herpesvirus Workshop.
Place of Presentation
神戸コンベンションセンター(兵庫県神戸市)
Year and Date
2014-07-19 – 2014-07-23
Related Report
-
[Presentation] 単純ヘルペスウイルスの標的化改変プラットフォームへのがん標的化抗体インハウスリソースの適用2013
Author(s)
柴田智子, 鈴木拓真, 大久保優, 駒井麻央, 福原武志, 山口美樹, 平井幸恵, 宮川世志幸, Justus Cohen, Joseph Glorioso, 濱田洋文, 内田宏昭
Organizer
第61回日本ウイルス学会学術集会
Place of Presentation
神戸
Related Report
-
[Presentation] エンベロープ糖タンパクgDにがん標的化単鎖抗体を挿入した単純ヘルペスウイルスを用いた腫瘍溶解ウイルス療法の開発2013
Author(s)
鈴木拓真, 柴田智子, 大久保優, 福原武志, 宮川世志幸, Justus Cohen, Joseph Glorioso, 中野賢二, 熊谷泉, 黒木政秀, 山口美樹, 平井幸恵, 濱田洋文, 内田宏昭
Organizer
第61回日本ウイルス学会学術集会
Place of Presentation
神戸
Related Report
-
-
[Presentation] Application of in-house monoclonal antibody resources to a fully retargeted oncolytic herpes simplex virus platform.2013
Author(s)
Okubo Y, Suzuki T, Shibata T, Komai M, Fukuhara T, Yamaguchi M, Hirai S, Miyagawa Y, Cohen JB, Glorioso JC, Hamada H, Uchida H.
Organizer
第72回日本癌学会学術総会
Place of Presentation
横浜
Related Report
-
-