Potent anti-tumor effects of receptor-retargeted syncytial oncolytic herpes simplex virus

Most oncolytic virotherapy has thus far employed viruses deficient in genes essential for replication in normal cells but not in cancer cells. Intra-tumoral injection of such viruses has resulted in clinically significant anti-tumor effects on the lesions in the vicinity of the injection sites but n...
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Autor*in:	Takuma Suzuki [verfasserIn] Hiroaki Uchida [verfasserIn] Tomoko Shibata [verfasserIn] Yasuhiko Sasaki [verfasserIn] Hitomi Ikeda [verfasserIn] Mika Hamada-Uematsu [verfasserIn] Ryota Hamasaki [verfasserIn] Kosaku Okuda [verfasserIn] Shigeru Yanagi [verfasserIn] Hideaki Tahara [verfasserIn]

Format:	E-Artikel
Sprache:	Englisch

Erschienen:	2021

Schlagwörter:	oncolytic virotherapy gene therapy cancer herpes simplex virus targeting HSV

Übergeordnetes Werk:	In: Molecular Therapy: Oncolytics - Elsevier, 2016, 22(2021), Seite 265-276
Übergeordnetes Werk:	volume:22 ; year:2021 ; pages:265-276

Links:	Link aufrufen Link aufrufen Link aufrufen Journal toc

DOI / URN:	10.1016/j.omto.2021.08.002

Katalog-ID:	DOAJ062273086

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spelling	10.1016/j.omto.2021.08.002 doi (DE-627)DOAJ062273086 (DE-599)DOAJca4b98d0ead84764b3142f271e88d857 DE-627 ger DE-627 rakwb eng RC254-282 Takuma Suzuki verfasserin aut Potent anti-tumor effects of receptor-retargeted syncytial oncolytic herpes simplex virus 2021 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier Most oncolytic virotherapy has thus far employed viruses deficient in genes essential for replication in normal cells but not in cancer cells. Intra-tumoral injection of such viruses has resulted in clinically significant anti-tumor effects on the lesions in the vicinity of the injection sites but not on distant visceral metastases. To overcome this limitation, we have developed a receptor-retargeted oncolytic herpes simplex virus employing a single-chain antibody for targeting tumor-associated antigens (RR-oHSV) and its modified version with additional mutations conferring syncytium formation (RRsyn-oHSV). We previously showed that RRsyn-oHSV exhibits preserved antigen specificity and an ∼20-fold higher tumoricidal potency in vitro relative to RR-oHSV. Here, we investigated the in vivo anti-tumor effects of RRsyn-oHSV using human cancer xenografts in immunodeficient mice. With only a single intra-tumoral injection of RRsyn-oHSV at very low doses, all treated tumors regressed completely. Furthermore, intra-venous administration of RRsyn-oHSV resulted in robust anti-tumor effects even against large tumors. We found that these potent anti-tumor effects of RRsyn-oHSV may be associated with the formation of long-lasting tumor cell syncytia not containing non-cancerous cells that appear to trigger death of the syncytia. These results strongly suggest that cancer patients with distant metastases could be effectively treated with our RRsyn-oHSV. oncolytic virotherapy gene therapy cancer herpes simplex virus targeting HSV Neoplasms. Tumors. Oncology. Including cancer and carcinogens Hiroaki Uchida verfasserin aut Tomoko Shibata verfasserin aut Yasuhiko Sasaki verfasserin aut Hitomi Ikeda verfasserin aut Mika Hamada-Uematsu verfasserin aut Ryota Hamasaki verfasserin aut Kosaku Okuda verfasserin aut Shigeru Yanagi verfasserin aut Hideaki Tahara verfasserin aut In Molecular Therapy: Oncolytics Elsevier, 2016 22(2021), Seite 265-276 (DE-627)843857420 (DE-600)2842549-2 23727705 nnns volume:22 year:2021 pages:265-276 https://doi.org/10.1016/j.omto.2021.08.002 kostenfrei https://doaj.org/article/ca4b98d0ead84764b3142f271e88d857 kostenfrei http://www.sciencedirect.com/science/article/pii/S2372770521001133 kostenfrei https://doaj.org/toc/2372-7705 Journal toc kostenfrei GBV_USEFLAG_A SYSFLAG_A GBV_DOAJ GBV_ILN_20 GBV_ILN_22 GBV_ILN_23 GBV_ILN_24 GBV_ILN_31 GBV_ILN_39 GBV_ILN_40 GBV_ILN_60 GBV_ILN_62 GBV_ILN_63 GBV_ILN_65 GBV_ILN_69 GBV_ILN_73 GBV_ILN_74 GBV_ILN_95 GBV_ILN_105 GBV_ILN_110 GBV_ILN_151 GBV_ILN_161 GBV_ILN_170 GBV_ILN_206 GBV_ILN_213 GBV_ILN_230 GBV_ILN_285 GBV_ILN_293 GBV_ILN_602 GBV_ILN_2014 GBV_ILN_4012 GBV_ILN_4037 GBV_ILN_4112 GBV_ILN_4125 GBV_ILN_4126 GBV_ILN_4249 GBV_ILN_4305 GBV_ILN_4306 GBV_ILN_4307 GBV_ILN_4313 GBV_ILN_4322 GBV_ILN_4323 GBV_ILN_4324 GBV_ILN_4325 GBV_ILN_4338 GBV_ILN_4367 GBV_ILN_4700 AR 22 2021 265-276
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allfieldsGer	10.1016/j.omto.2021.08.002 doi (DE-627)DOAJ062273086 (DE-599)DOAJca4b98d0ead84764b3142f271e88d857 DE-627 ger DE-627 rakwb eng RC254-282 Takuma Suzuki verfasserin aut Potent anti-tumor effects of receptor-retargeted syncytial oncolytic herpes simplex virus 2021 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier Most oncolytic virotherapy has thus far employed viruses deficient in genes essential for replication in normal cells but not in cancer cells. Intra-tumoral injection of such viruses has resulted in clinically significant anti-tumor effects on the lesions in the vicinity of the injection sites but not on distant visceral metastases. To overcome this limitation, we have developed a receptor-retargeted oncolytic herpes simplex virus employing a single-chain antibody for targeting tumor-associated antigens (RR-oHSV) and its modified version with additional mutations conferring syncytium formation (RRsyn-oHSV). We previously showed that RRsyn-oHSV exhibits preserved antigen specificity and an ∼20-fold higher tumoricidal potency in vitro relative to RR-oHSV. Here, we investigated the in vivo anti-tumor effects of RRsyn-oHSV using human cancer xenografts in immunodeficient mice. With only a single intra-tumoral injection of RRsyn-oHSV at very low doses, all treated tumors regressed completely. Furthermore, intra-venous administration of RRsyn-oHSV resulted in robust anti-tumor effects even against large tumors. We found that these potent anti-tumor effects of RRsyn-oHSV may be associated with the formation of long-lasting tumor cell syncytia not containing non-cancerous cells that appear to trigger death of the syncytia. These results strongly suggest that cancer patients with distant metastases could be effectively treated with our RRsyn-oHSV. oncolytic virotherapy gene therapy cancer herpes simplex virus targeting HSV Neoplasms. Tumors. Oncology. Including cancer and carcinogens Hiroaki Uchida verfasserin aut Tomoko Shibata verfasserin aut Yasuhiko Sasaki verfasserin aut Hitomi Ikeda verfasserin aut Mika Hamada-Uematsu verfasserin aut Ryota Hamasaki verfasserin aut Kosaku Okuda verfasserin aut Shigeru Yanagi verfasserin aut Hideaki Tahara verfasserin aut In Molecular Therapy: Oncolytics Elsevier, 2016 22(2021), Seite 265-276 (DE-627)843857420 (DE-600)2842549-2 23727705 nnns volume:22 year:2021 pages:265-276 https://doi.org/10.1016/j.omto.2021.08.002 kostenfrei https://doaj.org/article/ca4b98d0ead84764b3142f271e88d857 kostenfrei http://www.sciencedirect.com/science/article/pii/S2372770521001133 kostenfrei https://doaj.org/toc/2372-7705 Journal toc kostenfrei GBV_USEFLAG_A SYSFLAG_A GBV_DOAJ GBV_ILN_20 GBV_ILN_22 GBV_ILN_23 GBV_ILN_24 GBV_ILN_31 GBV_ILN_39 GBV_ILN_40 GBV_ILN_60 GBV_ILN_62 GBV_ILN_63 GBV_ILN_65 GBV_ILN_69 GBV_ILN_73 GBV_ILN_74 GBV_ILN_95 GBV_ILN_105 GBV_ILN_110 GBV_ILN_151 GBV_ILN_161 GBV_ILN_170 GBV_ILN_206 GBV_ILN_213 GBV_ILN_230 GBV_ILN_285 GBV_ILN_293 GBV_ILN_602 GBV_ILN_2014 GBV_ILN_4012 GBV_ILN_4037 GBV_ILN_4112 GBV_ILN_4125 GBV_ILN_4126 GBV_ILN_4249 GBV_ILN_4305 GBV_ILN_4306 GBV_ILN_4307 GBV_ILN_4313 GBV_ILN_4322 GBV_ILN_4323 GBV_ILN_4324 GBV_ILN_4325 GBV_ILN_4338 GBV_ILN_4367 GBV_ILN_4700 AR 22 2021 265-276
allfieldsSound	10.1016/j.omto.2021.08.002 doi (DE-627)DOAJ062273086 (DE-599)DOAJca4b98d0ead84764b3142f271e88d857 DE-627 ger DE-627 rakwb eng RC254-282 Takuma Suzuki verfasserin aut Potent anti-tumor effects of receptor-retargeted syncytial oncolytic herpes simplex virus 2021 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier Most oncolytic virotherapy has thus far employed viruses deficient in genes essential for replication in normal cells but not in cancer cells. Intra-tumoral injection of such viruses has resulted in clinically significant anti-tumor effects on the lesions in the vicinity of the injection sites but not on distant visceral metastases. To overcome this limitation, we have developed a receptor-retargeted oncolytic herpes simplex virus employing a single-chain antibody for targeting tumor-associated antigens (RR-oHSV) and its modified version with additional mutations conferring syncytium formation (RRsyn-oHSV). We previously showed that RRsyn-oHSV exhibits preserved antigen specificity and an ∼20-fold higher tumoricidal potency in vitro relative to RR-oHSV. Here, we investigated the in vivo anti-tumor effects of RRsyn-oHSV using human cancer xenografts in immunodeficient mice. With only a single intra-tumoral injection of RRsyn-oHSV at very low doses, all treated tumors regressed completely. Furthermore, intra-venous administration of RRsyn-oHSV resulted in robust anti-tumor effects even against large tumors. We found that these potent anti-tumor effects of RRsyn-oHSV may be associated with the formation of long-lasting tumor cell syncytia not containing non-cancerous cells that appear to trigger death of the syncytia. These results strongly suggest that cancer patients with distant metastases could be effectively treated with our RRsyn-oHSV. oncolytic virotherapy gene therapy cancer herpes simplex virus targeting HSV Neoplasms. Tumors. Oncology. Including cancer and carcinogens Hiroaki Uchida verfasserin aut Tomoko Shibata verfasserin aut Yasuhiko Sasaki verfasserin aut Hitomi Ikeda verfasserin aut Mika Hamada-Uematsu verfasserin aut Ryota Hamasaki verfasserin aut Kosaku Okuda verfasserin aut Shigeru Yanagi verfasserin aut Hideaki Tahara verfasserin aut In Molecular Therapy: Oncolytics Elsevier, 2016 22(2021), Seite 265-276 (DE-627)843857420 (DE-600)2842549-2 23727705 nnns volume:22 year:2021 pages:265-276 https://doi.org/10.1016/j.omto.2021.08.002 kostenfrei https://doaj.org/article/ca4b98d0ead84764b3142f271e88d857 kostenfrei http://www.sciencedirect.com/science/article/pii/S2372770521001133 kostenfrei https://doaj.org/toc/2372-7705 Journal toc kostenfrei GBV_USEFLAG_A SYSFLAG_A GBV_DOAJ GBV_ILN_20 GBV_ILN_22 GBV_ILN_23 GBV_ILN_24 GBV_ILN_31 GBV_ILN_39 GBV_ILN_40 GBV_ILN_60 GBV_ILN_62 GBV_ILN_63 GBV_ILN_65 GBV_ILN_69 GBV_ILN_73 GBV_ILN_74 GBV_ILN_95 GBV_ILN_105 GBV_ILN_110 GBV_ILN_151 GBV_ILN_161 GBV_ILN_170 GBV_ILN_206 GBV_ILN_213 GBV_ILN_230 GBV_ILN_285 GBV_ILN_293 GBV_ILN_602 GBV_ILN_2014 GBV_ILN_4012 GBV_ILN_4037 GBV_ILN_4112 GBV_ILN_4125 GBV_ILN_4126 GBV_ILN_4249 GBV_ILN_4305 GBV_ILN_4306 GBV_ILN_4307 GBV_ILN_4313 GBV_ILN_4322 GBV_ILN_4323 GBV_ILN_4324 GBV_ILN_4325 GBV_ILN_4338 GBV_ILN_4367 GBV_ILN_4700 AR 22 2021 265-276
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source	In Molecular Therapy: Oncolytics 22(2021), Seite 265-276 volume:22 year:2021 pages:265-276
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authorswithroles_txt_mv	Takuma Suzuki @@aut@@ Hiroaki Uchida @@aut@@ Tomoko Shibata @@aut@@ Yasuhiko Sasaki @@aut@@ Hitomi Ikeda @@aut@@ Mika Hamada-Uematsu @@aut@@ Ryota Hamasaki @@aut@@ Kosaku Okuda @@aut@@ Shigeru Yanagi @@aut@@ Hideaki Tahara @@aut@@
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callnumber-first	R - Medicine
author	Takuma Suzuki
spellingShingle	Takuma Suzuki misc RC254-282 misc oncolytic virotherapy misc gene therapy misc cancer misc herpes simplex virus misc targeting misc HSV misc Neoplasms. Tumors. Oncology. Including cancer and carcinogens Potent anti-tumor effects of receptor-retargeted syncytial oncolytic herpes simplex virus
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topic_title	RC254-282 Potent anti-tumor effects of receptor-retargeted syncytial oncolytic herpes simplex virus oncolytic virotherapy gene therapy cancer herpes simplex virus targeting HSV
topic	misc RC254-282 misc oncolytic virotherapy misc gene therapy misc cancer misc herpes simplex virus misc targeting misc HSV misc Neoplasms. Tumors. Oncology. Including cancer and carcinogens
topic_unstemmed	misc RC254-282 misc oncolytic virotherapy misc gene therapy misc cancer misc herpes simplex virus misc targeting misc HSV misc Neoplasms. Tumors. Oncology. Including cancer and carcinogens
topic_browse	misc RC254-282 misc oncolytic virotherapy misc gene therapy misc cancer misc herpes simplex virus misc targeting misc HSV misc Neoplasms. Tumors. Oncology. Including cancer and carcinogens
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title	Potent anti-tumor effects of receptor-retargeted syncytial oncolytic herpes simplex virus
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title_full	Potent anti-tumor effects of receptor-retargeted syncytial oncolytic herpes simplex virus
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author_browse	Takuma Suzuki Hiroaki Uchida Tomoko Shibata Yasuhiko Sasaki Hitomi Ikeda Mika Hamada-Uematsu Ryota Hamasaki Kosaku Okuda Shigeru Yanagi Hideaki Tahara
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title_sort	potent anti-tumor effects of receptor-retargeted syncytial oncolytic herpes simplex virus
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title_auth	Potent anti-tumor effects of receptor-retargeted syncytial oncolytic herpes simplex virus
abstract	Most oncolytic virotherapy has thus far employed viruses deficient in genes essential for replication in normal cells but not in cancer cells. Intra-tumoral injection of such viruses has resulted in clinically significant anti-tumor effects on the lesions in the vicinity of the injection sites but not on distant visceral metastases. To overcome this limitation, we have developed a receptor-retargeted oncolytic herpes simplex virus employing a single-chain antibody for targeting tumor-associated antigens (RR-oHSV) and its modified version with additional mutations conferring syncytium formation (RRsyn-oHSV). We previously showed that RRsyn-oHSV exhibits preserved antigen specificity and an ∼20-fold higher tumoricidal potency in vitro relative to RR-oHSV. Here, we investigated the in vivo anti-tumor effects of RRsyn-oHSV using human cancer xenografts in immunodeficient mice. With only a single intra-tumoral injection of RRsyn-oHSV at very low doses, all treated tumors regressed completely. Furthermore, intra-venous administration of RRsyn-oHSV resulted in robust anti-tumor effects even against large tumors. We found that these potent anti-tumor effects of RRsyn-oHSV may be associated with the formation of long-lasting tumor cell syncytia not containing non-cancerous cells that appear to trigger death of the syncytia. These results strongly suggest that cancer patients with distant metastases could be effectively treated with our RRsyn-oHSV.
abstractGer	Most oncolytic virotherapy has thus far employed viruses deficient in genes essential for replication in normal cells but not in cancer cells. Intra-tumoral injection of such viruses has resulted in clinically significant anti-tumor effects on the lesions in the vicinity of the injection sites but not on distant visceral metastases. To overcome this limitation, we have developed a receptor-retargeted oncolytic herpes simplex virus employing a single-chain antibody for targeting tumor-associated antigens (RR-oHSV) and its modified version with additional mutations conferring syncytium formation (RRsyn-oHSV). We previously showed that RRsyn-oHSV exhibits preserved antigen specificity and an ∼20-fold higher tumoricidal potency in vitro relative to RR-oHSV. Here, we investigated the in vivo anti-tumor effects of RRsyn-oHSV using human cancer xenografts in immunodeficient mice. With only a single intra-tumoral injection of RRsyn-oHSV at very low doses, all treated tumors regressed completely. Furthermore, intra-venous administration of RRsyn-oHSV resulted in robust anti-tumor effects even against large tumors. We found that these potent anti-tumor effects of RRsyn-oHSV may be associated with the formation of long-lasting tumor cell syncytia not containing non-cancerous cells that appear to trigger death of the syncytia. These results strongly suggest that cancer patients with distant metastases could be effectively treated with our RRsyn-oHSV.
abstract_unstemmed	Most oncolytic virotherapy has thus far employed viruses deficient in genes essential for replication in normal cells but not in cancer cells. Intra-tumoral injection of such viruses has resulted in clinically significant anti-tumor effects on the lesions in the vicinity of the injection sites but not on distant visceral metastases. To overcome this limitation, we have developed a receptor-retargeted oncolytic herpes simplex virus employing a single-chain antibody for targeting tumor-associated antigens (RR-oHSV) and its modified version with additional mutations conferring syncytium formation (RRsyn-oHSV). We previously showed that RRsyn-oHSV exhibits preserved antigen specificity and an ∼20-fold higher tumoricidal potency in vitro relative to RR-oHSV. Here, we investigated the in vivo anti-tumor effects of RRsyn-oHSV using human cancer xenografts in immunodeficient mice. With only a single intra-tumoral injection of RRsyn-oHSV at very low doses, all treated tumors regressed completely. Furthermore, intra-venous administration of RRsyn-oHSV resulted in robust anti-tumor effects even against large tumors. We found that these potent anti-tumor effects of RRsyn-oHSV may be associated with the formation of long-lasting tumor cell syncytia not containing non-cancerous cells that appear to trigger death of the syncytia. These results strongly suggest that cancer patients with distant metastases could be effectively treated with our RRsyn-oHSV.
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title_short	Potent anti-tumor effects of receptor-retargeted syncytial oncolytic herpes simplex virus
url	https://doi.org/10.1016/j.omto.2021.08.002 https://doaj.org/article/ca4b98d0ead84764b3142f271e88d857 http://www.sciencedirect.com/science/article/pii/S2372770521001133 https://doaj.org/toc/2372-7705
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author2	Hiroaki Uchida Tomoko Shibata Yasuhiko Sasaki Hitomi Ikeda Mika Hamada-Uematsu Ryota Hamasaki Kosaku Okuda Shigeru Yanagi Hideaki Tahara
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up_date	2024-07-04T00:59:26.619Z
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Potent anti-tumor effects of receptor-retargeted syncytial oncolytic herpes simplex virus

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