Efficacy and safety of a third-generation oncolytic herpes virus G47Δ in models of human esophageal carcinoma

Treatment options are limited for esophageal carcinoma (EC). G47Δ, a triple-mutated, conditionally replicating herpes simplex virus type 1 (HSV-1), exhibits enhanced killing of tumor cells with high safety features. Here, we studied the efficacy of G47Δ using preclinical models of human EC. In vitro...

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Autores principales:	Shoh Yajima, Kotaro Sugawara, Miwako Iwai, Minoru Tanaka, Yasuyuki Seto, Tomoki Todo
Formato:	article
Lenguaje:	EN
Publicado:	Elsevier 2021
Materias:	oncolytic virus therapy G47Δ esophageal cancer preclinical safety orthotopic tumor model herpes simplex virus Neoplasms. Tumors. Oncology. Including cancer and carcinogens RC254-282
Acceso en línea:	https://doaj.org/article/c492565af8014788be17816c26cc0ab9
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spelling	oai:doaj.org-article:c492565af8014788be17816c26cc0ab92021-11-14T04:34:27ZEfficacy and safety of a third-generation oncolytic herpes virus G47Δ in models of human esophageal carcinoma2372-770510.1016/j.omto.2021.10.012https://doaj.org/article/c492565af8014788be17816c26cc0ab92021-12-01T00:00:00Zhttp://www.sciencedirect.com/science/article/pii/S2372770521001492https://doaj.org/toc/2372-7705Treatment options are limited for esophageal carcinoma (EC). G47Δ, a triple-mutated, conditionally replicating herpes simplex virus type 1 (HSV-1), exhibits enhanced killing of tumor cells with high safety features. Here, we studied the efficacy of G47Δ using preclinical models of human EC. In vitro, G47Δ showed efficient cytopathic effects and replication capabilities in all eight human esophageal cancer cell lines tested. In athymic mice harboring subcutaneous tumors of human EC (KYSE180, TE8, and OE19), two intratumoral injections with G47Δ significantly inhibited the tumor growth. To mimic the clinical treatment situations, we established an orthotopic EC model using luciferase-expressing TE8 cells (TE8-luc). An intratumoral injection with G47Δ markedly inhibited the growth of orthotopic TE8-luc tumors in athymic mice. Furthermore, we evaluated the safety of applying G47Δ to the esophagus in mice. A/J mice inoculated intraesophageally or administered orally with G47Δ (107 plaque-forming units [pfu]) survived for more than 2 months without remarkable symptoms, whereas the majority with wild-type HSV-1 (106 pfu) deteriorated within 10 days. PCR analyses showed that the G47Δ DNA was confined to the esophagus after intraesophageal inoculation and was not detected in major organs after oral administration. Our results provide a rationale for the clinical use of G47Δ for treating EC.Shoh YajimaKotaro SugawaraMiwako IwaiMinoru TanakaYasuyuki SetoTomoki TodoElsevierarticleoncolytic virus therapyG47Δesophageal cancerpreclinical safetyorthotopic tumor modelherpes simplex virusNeoplasms. Tumors. Oncology. Including cancer and carcinogensRC254-282ENMolecular Therapy: Oncolytics, Vol 23, Iss , Pp 402-411 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	oncolytic virus therapy G47Δ esophageal cancer preclinical safety orthotopic tumor model herpes simplex virus Neoplasms. Tumors. Oncology. Including cancer and carcinogens RC254-282
spellingShingle	oncolytic virus therapy G47Δ esophageal cancer preclinical safety orthotopic tumor model herpes simplex virus Neoplasms. Tumors. Oncology. Including cancer and carcinogens RC254-282 Shoh Yajima Kotaro Sugawara Miwako Iwai Minoru Tanaka Yasuyuki Seto Tomoki Todo Efficacy and safety of a third-generation oncolytic herpes virus G47Δ in models of human esophageal carcinoma
description	Treatment options are limited for esophageal carcinoma (EC). G47Δ, a triple-mutated, conditionally replicating herpes simplex virus type 1 (HSV-1), exhibits enhanced killing of tumor cells with high safety features. Here, we studied the efficacy of G47Δ using preclinical models of human EC. In vitro, G47Δ showed efficient cytopathic effects and replication capabilities in all eight human esophageal cancer cell lines tested. In athymic mice harboring subcutaneous tumors of human EC (KYSE180, TE8, and OE19), two intratumoral injections with G47Δ significantly inhibited the tumor growth. To mimic the clinical treatment situations, we established an orthotopic EC model using luciferase-expressing TE8 cells (TE8-luc). An intratumoral injection with G47Δ markedly inhibited the growth of orthotopic TE8-luc tumors in athymic mice. Furthermore, we evaluated the safety of applying G47Δ to the esophagus in mice. A/J mice inoculated intraesophageally or administered orally with G47Δ (107 plaque-forming units [pfu]) survived for more than 2 months without remarkable symptoms, whereas the majority with wild-type HSV-1 (106 pfu) deteriorated within 10 days. PCR analyses showed that the G47Δ DNA was confined to the esophagus after intraesophageal inoculation and was not detected in major organs after oral administration. Our results provide a rationale for the clinical use of G47Δ for treating EC.
format	article
author	Shoh Yajima Kotaro Sugawara Miwako Iwai Minoru Tanaka Yasuyuki Seto Tomoki Todo
author_facet	Shoh Yajima Kotaro Sugawara Miwako Iwai Minoru Tanaka Yasuyuki Seto Tomoki Todo
author_sort	Shoh Yajima
title	Efficacy and safety of a third-generation oncolytic herpes virus G47Δ in models of human esophageal carcinoma
title_short	Efficacy and safety of a third-generation oncolytic herpes virus G47Δ in models of human esophageal carcinoma
title_full	Efficacy and safety of a third-generation oncolytic herpes virus G47Δ in models of human esophageal carcinoma
title_fullStr	Efficacy and safety of a third-generation oncolytic herpes virus G47Δ in models of human esophageal carcinoma
title_full_unstemmed	Efficacy and safety of a third-generation oncolytic herpes virus G47Δ in models of human esophageal carcinoma
title_sort	efficacy and safety of a third-generation oncolytic herpes virus g47δ in models of human esophageal carcinoma
publisher	Elsevier
publishDate	2021
url	https://doaj.org/article/c492565af8014788be17816c26cc0ab9
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Efficacy and safety of a third-generation oncolytic herpes virus G47Δ in models of human esophageal carcinoma

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