Mechanisms that allow vaccination against an oncolytic vesicular stomatitis virus-encoded transgene to enhance safety without abrogating oncolysis

Abstract Vaccination can prevent viral infections via virus-specific T cells, among other mechanisms. A goal of oncolytic virotherapy is replication of oncolytic viruses (OVs) in tumors, so pre-existing T cell immunity against an OV-encoded transgene would seem counterproductive. We developed a trea...

Descripción completa

Guardado en:

Detalles Bibliográficos
Autores principales:	Amanda W. K. AuYeung, Robert C. Mould, Ashley A. Stegelmeier, Jacob P. van Vloten, Khalil Karimi, J. Paul Woods, James J. Petrik, Geoffrey A. Wood, Byram W. Bridle
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2021
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/cc74d8086b614168938f0bb79a7adef3
Etiquetas:	Agregar Etiqueta Sin Etiquetas, Sea el primero en etiquetar este registro!

id	oai:doaj.org-article:cc74d8086b614168938f0bb79a7adef3
record_format	dspace
spelling	oai:doaj.org-article:cc74d8086b614168938f0bb79a7adef32021-12-02T16:23:42ZMechanisms that allow vaccination against an oncolytic vesicular stomatitis virus-encoded transgene to enhance safety without abrogating oncolysis10.1038/s41598-021-94483-z2045-2322https://doaj.org/article/cc74d8086b614168938f0bb79a7adef32021-07-01T00:00:00Zhttps://doi.org/10.1038/s41598-021-94483-zhttps://doaj.org/toc/2045-2322Abstract Vaccination can prevent viral infections via virus-specific T cells, among other mechanisms. A goal of oncolytic virotherapy is replication of oncolytic viruses (OVs) in tumors, so pre-existing T cell immunity against an OV-encoded transgene would seem counterproductive. We developed a treatment for melanomas by pre-vaccinating against an oncolytic vesicular stomatitis virus (VSV)-encoded tumor antigen. Surprisingly, when the VSV-vectored booster vaccine was administered at the peak of the primary effector T cell response, oncolysis was not abrogated. We sought to determine how oncolysis was retained during a robust T cell response against the VSV-encoded transgene product. A murine melanoma model was used to identify two mechanisms that enable this phenomenon. First, tumor-infiltrating T cells had reduced cytopathic potential due to immunosuppression. Second, virus-induced lymphopenia acutely removed virus-specific T cells from tumors. These mechanisms provide a window of opportunity for replication of oncolytic VSV and rationale for a paradigm change in oncolytic virotherapy, whereby immune responses could be intentionally induced against a VSV-encoded melanoma-associated antigen to improve safety without abrogating oncolysis.Amanda W. K. AuYeungRobert C. MouldAshley A. StegelmeierJacob P. van VlotenKhalil KarimiJ. Paul WoodsJames J. PetrikGeoffrey A. WoodByram W. BridleNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 11, Iss 1, Pp 1-14 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Amanda W. K. AuYeung Robert C. Mould Ashley A. Stegelmeier Jacob P. van Vloten Khalil Karimi J. Paul Woods James J. Petrik Geoffrey A. Wood Byram W. Bridle Mechanisms that allow vaccination against an oncolytic vesicular stomatitis virus-encoded transgene to enhance safety without abrogating oncolysis
description	Abstract Vaccination can prevent viral infections via virus-specific T cells, among other mechanisms. A goal of oncolytic virotherapy is replication of oncolytic viruses (OVs) in tumors, so pre-existing T cell immunity against an OV-encoded transgene would seem counterproductive. We developed a treatment for melanomas by pre-vaccinating against an oncolytic vesicular stomatitis virus (VSV)-encoded tumor antigen. Surprisingly, when the VSV-vectored booster vaccine was administered at the peak of the primary effector T cell response, oncolysis was not abrogated. We sought to determine how oncolysis was retained during a robust T cell response against the VSV-encoded transgene product. A murine melanoma model was used to identify two mechanisms that enable this phenomenon. First, tumor-infiltrating T cells had reduced cytopathic potential due to immunosuppression. Second, virus-induced lymphopenia acutely removed virus-specific T cells from tumors. These mechanisms provide a window of opportunity for replication of oncolytic VSV and rationale for a paradigm change in oncolytic virotherapy, whereby immune responses could be intentionally induced against a VSV-encoded melanoma-associated antigen to improve safety without abrogating oncolysis.
format	article
author	Amanda W. K. AuYeung Robert C. Mould Ashley A. Stegelmeier Jacob P. van Vloten Khalil Karimi J. Paul Woods James J. Petrik Geoffrey A. Wood Byram W. Bridle
author_facet	Amanda W. K. AuYeung Robert C. Mould Ashley A. Stegelmeier Jacob P. van Vloten Khalil Karimi J. Paul Woods James J. Petrik Geoffrey A. Wood Byram W. Bridle
author_sort	Amanda W. K. AuYeung
title	Mechanisms that allow vaccination against an oncolytic vesicular stomatitis virus-encoded transgene to enhance safety without abrogating oncolysis
title_short	Mechanisms that allow vaccination against an oncolytic vesicular stomatitis virus-encoded transgene to enhance safety without abrogating oncolysis
title_full	Mechanisms that allow vaccination against an oncolytic vesicular stomatitis virus-encoded transgene to enhance safety without abrogating oncolysis
title_fullStr	Mechanisms that allow vaccination against an oncolytic vesicular stomatitis virus-encoded transgene to enhance safety without abrogating oncolysis
title_full_unstemmed	Mechanisms that allow vaccination against an oncolytic vesicular stomatitis virus-encoded transgene to enhance safety without abrogating oncolysis
title_sort	mechanisms that allow vaccination against an oncolytic vesicular stomatitis virus-encoded transgene to enhance safety without abrogating oncolysis
publisher	Nature Portfolio
publishDate	2021
url	https://doaj.org/article/cc74d8086b614168938f0bb79a7adef3
work_keys_str_mv	AT amandawkauyeung mechanismsthatallowvaccinationagainstanoncolyticvesicularstomatitisvirusencodedtransgenetoenhancesafetywithoutabrogatingoncolysis AT robertcmould mechanismsthatallowvaccinationagainstanoncolyticvesicularstomatitisvirusencodedtransgenetoenhancesafetywithoutabrogatingoncolysis AT ashleyastegelmeier mechanismsthatallowvaccinationagainstanoncolyticvesicularstomatitisvirusencodedtransgenetoenhancesafetywithoutabrogatingoncolysis AT jacobpvanvloten mechanismsthatallowvaccinationagainstanoncolyticvesicularstomatitisvirusencodedtransgenetoenhancesafetywithoutabrogatingoncolysis AT khalilkarimi mechanismsthatallowvaccinationagainstanoncolyticvesicularstomatitisvirusencodedtransgenetoenhancesafetywithoutabrogatingoncolysis AT jpaulwoods mechanismsthatallowvaccinationagainstanoncolyticvesicularstomatitisvirusencodedtransgenetoenhancesafetywithoutabrogatingoncolysis AT jamesjpetrik mechanismsthatallowvaccinationagainstanoncolyticvesicularstomatitisvirusencodedtransgenetoenhancesafetywithoutabrogatingoncolysis AT geoffreyawood mechanismsthatallowvaccinationagainstanoncolyticvesicularstomatitisvirusencodedtransgenetoenhancesafetywithoutabrogatingoncolysis AT byramwbridle mechanismsthatallowvaccinationagainstanoncolyticvesicularstomatitisvirusencodedtransgenetoenhancesafetywithoutabrogatingoncolysis
_version_	1718384138372775936

Mechanisms that allow vaccination against an oncolytic vesicular stomatitis virus-encoded transgene to enhance safety without abrogating oncolysis

Ejemplares similares