Cytokine-modified VSV is attenuated for neural pathology, but is both highly immunogenic and oncolytic

J. Miller, S. M. Bidula, T. M. Jensen, C. S. Reiss

Research output: Contribution to journalArticle

Abstract

Vesicular stomatitis virus (VSV), an enveloped, nonsegmented, negative-stranded RNA virus, is being tested by several laboratories as an antitumor agent. Unfortunately, viral infection of the central nervous system (CNS) has been observed by many groups following administration to tumor-bearing animals. In rodents, VSV encephalitis is characterized by weight-loss, paralysis, and high mortality. In order to provide protection from VSV infection of the CNS after therapeutic administration, we have attenuated VSV by the introduction of the gene encoding the proinflammatory cytokine interleukin (IL)-23, and designated the new virus VSV23. We hypothesize that while VSV23 is replicating within tumors, resulting in tumor destruction, the expression of IL-23 will enhance host antitumor and antiviral immune responses. In the event that the virus escapes from the tumor, the host's immune system will be activated and the virus will be rapidly cleared from healthy tissue. Experimental VSV23 infection of the CNS is characterized by decreased viral replication, morbidity, and mortality. VSV23 is capable of stimulating the enhanced production of nitric oxide in the CNS, which is critical for elimination of VSV from infected neurons. Intraperitoneal administration of VSV23 stimulates both nonspecific natural killer cell, virus-specific cytolytic T lymphocyte and memory virus-specific proliferative T cell responses against wild-type VSV in splenocytes. Furthermore, VSV23 is able to replicate in, and induce apoptosis of tumor cells in vitro. These data indicate that VSV23 is immunogenic, attenuated and suitable for testing as an efficacious and safe oncolytic agent.
Original languageUndefined
Pages (from-to)15-32
Number of pages18
JournalInternational Journal of Interferon, Cytokine and Mediator Research
Volume1
StatePublished - 2009

Cite this

Cytokine-modified VSV is attenuated for neural pathology, but is both highly immunogenic and oncolytic. / Miller, J.; Bidula, S. M.; Jensen, T. M.; Reiss, C. S.

In: International Journal of Interferon, Cytokine and Mediator Research, Vol. 1, 2009, p. 15-32.

Research output: Contribution to journalArticle

@article{3c4a0607df554ea895da4d0b00ced992,
title = "Cytokine-modified VSV is attenuated for neural pathology, but is both highly immunogenic and oncolytic",
abstract = "Vesicular stomatitis virus (VSV), an enveloped, nonsegmented, negative-stranded RNA virus, is being tested by several laboratories as an antitumor agent. Unfortunately, viral infection of the central nervous system (CNS) has been observed by many groups following administration to tumor-bearing animals. In rodents, VSV encephalitis is characterized by weight-loss, paralysis, and high mortality. In order to provide protection from VSV infection of the CNS after therapeutic administration, we have attenuated VSV by the introduction of the gene encoding the proinflammatory cytokine interleukin (IL)-23, and designated the new virus VSV23. We hypothesize that while VSV23 is replicating within tumors, resulting in tumor destruction, the expression of IL-23 will enhance host antitumor and antiviral immune responses. In the event that the virus escapes from the tumor, the host's immune system will be activated and the virus will be rapidly cleared from healthy tissue. Experimental VSV23 infection of the CNS is characterized by decreased viral replication, morbidity, and mortality. VSV23 is capable of stimulating the enhanced production of nitric oxide in the CNS, which is critical for elimination of VSV from infected neurons. Intraperitoneal administration of VSV23 stimulates both nonspecific natural killer cell, virus-specific cytolytic T lymphocyte and memory virus-specific proliferative T cell responses against wild-type VSV in splenocytes. Furthermore, VSV23 is able to replicate in, and induce apoptosis of tumor cells in vitro. These data indicate that VSV23 is immunogenic, attenuated and suitable for testing as an efficacious and safe oncolytic agent.",
author = "J. Miller and Bidula, {S. M.} and Jensen, {T. M.} and Reiss, {C. S.}",
note = "Miller, James Bidula, Sarah M Jensen, Troels M Reiss, Carol Shoshkes R01 NS039746/NS/NINDS NIH HHS/United States R01 NS039746-08/NS/NINDS NIH HHS/United States R01 NS039746-09/NS/NINDS NIH HHS/United States Journal article Int J Infereron Cytokine Mediator Res. 2009 Dec 1;1:15-32.",
year = "2009",
language = "Undefined",
volume = "1",
pages = "15--32",
journal = "International Journal of Interferon, Cytokine and Mediator Research",
issn = "1179-139X",

}

TY - JOUR

T1 - Cytokine-modified VSV is attenuated for neural pathology, but is both highly immunogenic and oncolytic

AU - Miller, J.

AU - Bidula, S. M.

AU - Jensen, T. M.

AU - Reiss, C. S.

N1 - Miller, James Bidula, Sarah M Jensen, Troels M Reiss, Carol Shoshkes R01 NS039746/NS/NINDS NIH HHS/United States R01 NS039746-08/NS/NINDS NIH HHS/United States R01 NS039746-09/NS/NINDS NIH HHS/United States Journal article Int J Infereron Cytokine Mediator Res. 2009 Dec 1;1:15-32.

PY - 2009

Y1 - 2009

N2 - Vesicular stomatitis virus (VSV), an enveloped, nonsegmented, negative-stranded RNA virus, is being tested by several laboratories as an antitumor agent. Unfortunately, viral infection of the central nervous system (CNS) has been observed by many groups following administration to tumor-bearing animals. In rodents, VSV encephalitis is characterized by weight-loss, paralysis, and high mortality. In order to provide protection from VSV infection of the CNS after therapeutic administration, we have attenuated VSV by the introduction of the gene encoding the proinflammatory cytokine interleukin (IL)-23, and designated the new virus VSV23. We hypothesize that while VSV23 is replicating within tumors, resulting in tumor destruction, the expression of IL-23 will enhance host antitumor and antiviral immune responses. In the event that the virus escapes from the tumor, the host's immune system will be activated and the virus will be rapidly cleared from healthy tissue. Experimental VSV23 infection of the CNS is characterized by decreased viral replication, morbidity, and mortality. VSV23 is capable of stimulating the enhanced production of nitric oxide in the CNS, which is critical for elimination of VSV from infected neurons. Intraperitoneal administration of VSV23 stimulates both nonspecific natural killer cell, virus-specific cytolytic T lymphocyte and memory virus-specific proliferative T cell responses against wild-type VSV in splenocytes. Furthermore, VSV23 is able to replicate in, and induce apoptosis of tumor cells in vitro. These data indicate that VSV23 is immunogenic, attenuated and suitable for testing as an efficacious and safe oncolytic agent.

AB - Vesicular stomatitis virus (VSV), an enveloped, nonsegmented, negative-stranded RNA virus, is being tested by several laboratories as an antitumor agent. Unfortunately, viral infection of the central nervous system (CNS) has been observed by many groups following administration to tumor-bearing animals. In rodents, VSV encephalitis is characterized by weight-loss, paralysis, and high mortality. In order to provide protection from VSV infection of the CNS after therapeutic administration, we have attenuated VSV by the introduction of the gene encoding the proinflammatory cytokine interleukin (IL)-23, and designated the new virus VSV23. We hypothesize that while VSV23 is replicating within tumors, resulting in tumor destruction, the expression of IL-23 will enhance host antitumor and antiviral immune responses. In the event that the virus escapes from the tumor, the host's immune system will be activated and the virus will be rapidly cleared from healthy tissue. Experimental VSV23 infection of the CNS is characterized by decreased viral replication, morbidity, and mortality. VSV23 is capable of stimulating the enhanced production of nitric oxide in the CNS, which is critical for elimination of VSV from infected neurons. Intraperitoneal administration of VSV23 stimulates both nonspecific natural killer cell, virus-specific cytolytic T lymphocyte and memory virus-specific proliferative T cell responses against wild-type VSV in splenocytes. Furthermore, VSV23 is able to replicate in, and induce apoptosis of tumor cells in vitro. These data indicate that VSV23 is immunogenic, attenuated and suitable for testing as an efficacious and safe oncolytic agent.

M3 - Article

VL - 1

SP - 15

EP - 32

JO - International Journal of Interferon, Cytokine and Mediator Research

JF - International Journal of Interferon, Cytokine and Mediator Research

SN - 1179-139X

ER -