Oncolytic potency of HER-2 retargeted VSV-FH hybrid viruses: the role of receptor ligand affinity

The hybrid oncolytic vesicular stomatitis virus (VSV-FH) deleted for its G glycoprotein and displaying the measles virus (MV) envelope glycoproteins (hemagglutinin H and fusion F) is fusogenic, infects cells via any of the three MV receptors and has potent oncolytic activity against subcutaneous and...

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Main Authors:	Ayala Breton, Camilo, Wikan, Nitwara, Abbuhl, Arinda, Smith, Duncan R, Russell, Stephen J, Peng, Kah-Whye
Format:	Online
Language:	English
Published:	Nature Publishing Group 2015
Online Access:	https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4782949/

id	pubmed-4782949
recordtype	oai_dc
spelling	pubmed-47829492016-04-26 Oncolytic potency of HER-2 retargeted VSV-FH hybrid viruses: the role of receptor ligand affinity Ayala Breton, Camilo Wikan, Nitwara Abbuhl, Arinda Smith, Duncan R Russell, Stephen J Peng, Kah-Whye Article The hybrid oncolytic vesicular stomatitis virus (VSV-FH) deleted for its G glycoprotein and displaying the measles virus (MV) envelope glycoproteins (hemagglutinin H and fusion F) is fusogenic, infects cells via any of the three MV receptors and has potent oncolytic activity against subcutaneous and disseminated myeloma tumors. To tailor VSV-FH as an oncolytic virus for ovarian cancer, we ablated its natural tropism and retargeted the virus by display of a single-chain antibody (scFv) with specificity to the HER-2/neu receptor. A panel of six VSVFH-αHER2 viruses displaying anti-HER2 scFv that bind to the same HER2 epitope but with different Kd (10−6 to 10−11 M, VSVFH-αHER2#6 to #11, respectively) were rescued and characterized. A Kd of at least 10−8 M is required for infection of HER-2 positive SKOV3ip.1 cells. The higher affinity viruses (>10−8 M) were able to infect and fuse SKOV3ip.1 cells more efficiently, inducing more extensive cytopathic effects. We next compared the antitumor potency of the viruses against SKOV3ip.1 tumor xenografts. In contrast to the saline-treated animals, one intratumoral injection of VSVFH-αHER2#9, #10, or #11 resulted in efficient tumor control. There was no significant difference between viruses with an affinity higher than 10−9 M in terms of oncolytic potency. VSVFH-αHER2 virus may be a promising agent for the treatment of HER-2 positive malignancies. Nature Publishing Group 2015-08-05 /pmc/articles/PMC4782949/ /pubmed/27119107 http://dx.doi.org/10.1038/mto.2015.12 Text en Copyright © 2015 American Society of Gene & Cell Therapy http://creativecommons.org/licenses/by-nc-nd/4.0/ This work is licensed under a Creative Commons Attribution-NonCommercial-NoDerivs 4.0 International License. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in the credit line; if the material is not included under the Creative Commons license, users will need to obtain permission from the license holder to reproduce the material. To view a copy of this license, visit http://creativecommons.org/licenses/by-nc-nd/4.0/
repository_type	Open Access Journal
institution_category	Foreign Institution
institution	US National Center for Biotechnology Information
building	NCBI PubMed
collection	Online Access
language	English
format	Online
author	Ayala Breton, Camilo Wikan, Nitwara Abbuhl, Arinda Smith, Duncan R Russell, Stephen J Peng, Kah-Whye
spellingShingle	Ayala Breton, Camilo Wikan, Nitwara Abbuhl, Arinda Smith, Duncan R Russell, Stephen J Peng, Kah-Whye Oncolytic potency of HER-2 retargeted VSV-FH hybrid viruses: the role of receptor ligand affinity
author_facet	Ayala Breton, Camilo Wikan, Nitwara Abbuhl, Arinda Smith, Duncan R Russell, Stephen J Peng, Kah-Whye
author_sort	Ayala Breton, Camilo
title	Oncolytic potency of HER-2 retargeted VSV-FH hybrid viruses: the role of receptor ligand affinity
title_short	Oncolytic potency of HER-2 retargeted VSV-FH hybrid viruses: the role of receptor ligand affinity
title_full	Oncolytic potency of HER-2 retargeted VSV-FH hybrid viruses: the role of receptor ligand affinity
title_fullStr	Oncolytic potency of HER-2 retargeted VSV-FH hybrid viruses: the role of receptor ligand affinity
title_full_unstemmed	Oncolytic potency of HER-2 retargeted VSV-FH hybrid viruses: the role of receptor ligand affinity
title_sort	oncolytic potency of her-2 retargeted vsv-fh hybrid viruses: the role of receptor ligand affinity
description	The hybrid oncolytic vesicular stomatitis virus (VSV-FH) deleted for its G glycoprotein and displaying the measles virus (MV) envelope glycoproteins (hemagglutinin H and fusion F) is fusogenic, infects cells via any of the three MV receptors and has potent oncolytic activity against subcutaneous and disseminated myeloma tumors. To tailor VSV-FH as an oncolytic virus for ovarian cancer, we ablated its natural tropism and retargeted the virus by display of a single-chain antibody (scFv) with specificity to the HER-2/neu receptor. A panel of six VSVFH-αHER2 viruses displaying anti-HER2 scFv that bind to the same HER2 epitope but with different Kd (10−6 to 10−11 M, VSVFH-αHER2#6 to #11, respectively) were rescued and characterized. A Kd of at least 10−8 M is required for infection of HER-2 positive SKOV3ip.1 cells. The higher affinity viruses (>10−8 M) were able to infect and fuse SKOV3ip.1 cells more efficiently, inducing more extensive cytopathic effects. We next compared the antitumor potency of the viruses against SKOV3ip.1 tumor xenografts. In contrast to the saline-treated animals, one intratumoral injection of VSVFH-αHER2#9, #10, or #11 resulted in efficient tumor control. There was no significant difference between viruses with an affinity higher than 10−9 M in terms of oncolytic potency. VSVFH-αHER2 virus may be a promising agent for the treatment of HER-2 positive malignancies.
publisher	Nature Publishing Group
publishDate	2015
url	https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4782949/
_version_	1613548960082821120

Oncolytic potency of HER-2 retargeted VSV-FH hybrid viruses: the role of receptor ligand affinity

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