Meningeal myeloma deposits adversely impact the therapeutic index of an oncolytic VSV

Meningeal myeloma deposits adversely impact the therapeutic index of an oncolytic VSV

Vesicular Stomatitis Virus (VSV) is neuropathogenic in rodents but can be attenuated 50-fold by engineering the mouse interferon-beta (IFN-β) gene into its genome. Intravenously administered VSVs encoding IFN-β have potent activity against subcutaneous tumors in the 5TGM1 mouse myeloma model, withou...

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Main Authors: Yarde, Danielle N., Naik, Shruthi, Nace, Rebecca A., Peng, Kah-Whye, Federspiel, Mark J., Russell, Stephen J.
Format: Online
Language:English
Published: 2013
Online Access:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3855306/
id pubmed-3855306
recordtype oai_dc
spelling pubmed-38553062014-05-01 Meningeal myeloma deposits adversely impact the therapeutic index of an oncolytic VSV Yarde, Danielle N. Naik, Shruthi Nace, Rebecca A. Peng, Kah-Whye Federspiel, Mark J. Russell, Stephen J. Article Vesicular Stomatitis Virus (VSV) is neuropathogenic in rodents but can be attenuated 50-fold by engineering the mouse interferon-beta (IFN-β) gene into its genome. Intravenously administered VSVs encoding IFN-β have potent activity against subcutaneous tumors in the 5TGM1 mouse myeloma model, without attendant neurotoxicity. However, when 5TGM1 tumor cells were seeded intravenously, virus-treated mice with advanced myeloma developed clinical signs suggestive of meningoencephalitis. Co-administration of a known active antimyeloma agent did not prolong survival, further suggesting that deaths were due to viral toxicity, not tumor burden. Histological analysis revealed that systemically administered 5TGM1 cells seed to the CNS forming meningeal tumor deposits and that VSV infects and destroys these tumors. Death is presumably a consequence of meningeal damage and/or direct transmission of virus to adjacent neural tissue. In light of these studies, extreme caution is warranted in clinical testing of attenuated VSVs, particularly in patients with CNS tumor deposits. 2013-11-01 2013-11 /pmc/articles/PMC3855306/ /pubmed/24176894 http://dx.doi.org/10.1038/cgt.2013.63 Text en Users may view, print, copy, download and text and data- mine the content in such documents, for the purposes of academic research, subject always to the full Conditions of use: http://www.nature.com/authors/editorial_policies/license.html#terms
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 Yarde, Danielle N.
Naik, Shruthi
Nace, Rebecca A.
Peng, Kah-Whye
Federspiel, Mark J.
Russell, Stephen J.
spellingShingle Yarde, Danielle N.
Naik, Shruthi
Nace, Rebecca A.
Peng, Kah-Whye
Federspiel, Mark J.
Russell, Stephen J.
Meningeal myeloma deposits adversely impact the therapeutic index of an oncolytic VSV
author_facet Yarde, Danielle N.
Naik, Shruthi
Nace, Rebecca A.
Peng, Kah-Whye
Federspiel, Mark J.
Russell, Stephen J.
author_sort Yarde, Danielle N.
title Meningeal myeloma deposits adversely impact the therapeutic index of an oncolytic VSV
title_short Meningeal myeloma deposits adversely impact the therapeutic index of an oncolytic VSV
title_full Meningeal myeloma deposits adversely impact the therapeutic index of an oncolytic VSV
title_fullStr Meningeal myeloma deposits adversely impact the therapeutic index of an oncolytic VSV
title_full_unstemmed Meningeal myeloma deposits adversely impact the therapeutic index of an oncolytic VSV
title_sort meningeal myeloma deposits adversely impact the therapeutic index of an oncolytic vsv
description Vesicular Stomatitis Virus (VSV) is neuropathogenic in rodents but can be attenuated 50-fold by engineering the mouse interferon-beta (IFN-β) gene into its genome. Intravenously administered VSVs encoding IFN-β have potent activity against subcutaneous tumors in the 5TGM1 mouse myeloma model, without attendant neurotoxicity. However, when 5TGM1 tumor cells were seeded intravenously, virus-treated mice with advanced myeloma developed clinical signs suggestive of meningoencephalitis. Co-administration of a known active antimyeloma agent did not prolong survival, further suggesting that deaths were due to viral toxicity, not tumor burden. Histological analysis revealed that systemically administered 5TGM1 cells seed to the CNS forming meningeal tumor deposits and that VSV infects and destroys these tumors. Death is presumably a consequence of meningeal damage and/or direct transmission of virus to adjacent neural tissue. In light of these studies, extreme caution is warranted in clinical testing of attenuated VSVs, particularly in patients with CNS tumor deposits.
publishDate 2013
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3855306/
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