TY - JOUR
T1 - Vesicular stomatitis virus modified with single chain IL-23 exhibits oncolytic activity against tumor cells in vitro and in vivo
AU - Miller, James M.
AU - Bidula, Sarah McNulty
AU - Jensen, Troels Mygind
AU - Reiss, Carol Shoshkes
N1 - Copyright:
Copyright 2010 Elsevier B.V., All rights reserved.
PY - 2010
Y1 - 2010
N2 - Viruses are potentially attractive agents for development as novel oncolytic agents. Reverse genetic approaches allow for the attenuation of candidate viruses and can enhance their ability to exploit inherent cellular and molecular properties of tumors, including deficiencies in interferon (IFN) signaling. Vesicular stomatitis virus (VSV) is a promising oncolytic agent for exactly these reasons. VSV infection of immunocompetent mice is usually rapidly cleared due to the virus' sensitivity to type I IFN responses. However, in tumors that are unable to activate the IFN response, VSV is able to replicate without inhibition, resulting in cell destruction. Unfortunately, when VSV is introduced into mice intranasally or systemically via therapeutic doses into tumor-bearing rodents, hosts may develop fatal encephalitis. We have previously found that a recombinant VSV expressing the pro-inflammatory cytokine interleukin-23 (IL-23) is significantly attenuated in the central nervous system (CNS). As a result of this, we hypothesized that attenuation in the CNS is partially a result of enhanced NO response as a result of IL-23 signaling. Infection of the CNS with this virus (designated VSV23) is characterized by decreased viral replication, morbidity, and mortality. We have now extended those studies which reveal that VSV23 maintains oncolytic capacity in vitro in multiple cell lines including NB41A3 neuroblastomas, L929 adipose-derived cells, immortalized BHK-21 cells, and the murine mammary derived JC cells. Additionally, in vivo VSV23 infection results in JC tumor destruction and induces enhanced memory responses against tumor cells.
AB - Viruses are potentially attractive agents for development as novel oncolytic agents. Reverse genetic approaches allow for the attenuation of candidate viruses and can enhance their ability to exploit inherent cellular and molecular properties of tumors, including deficiencies in interferon (IFN) signaling. Vesicular stomatitis virus (VSV) is a promising oncolytic agent for exactly these reasons. VSV infection of immunocompetent mice is usually rapidly cleared due to the virus' sensitivity to type I IFN responses. However, in tumors that are unable to activate the IFN response, VSV is able to replicate without inhibition, resulting in cell destruction. Unfortunately, when VSV is introduced into mice intranasally or systemically via therapeutic doses into tumor-bearing rodents, hosts may develop fatal encephalitis. We have previously found that a recombinant VSV expressing the pro-inflammatory cytokine interleukin-23 (IL-23) is significantly attenuated in the central nervous system (CNS). As a result of this, we hypothesized that attenuation in the CNS is partially a result of enhanced NO response as a result of IL-23 signaling. Infection of the CNS with this virus (designated VSV23) is characterized by decreased viral replication, morbidity, and mortality. We have now extended those studies which reveal that VSV23 maintains oncolytic capacity in vitro in multiple cell lines including NB41A3 neuroblastomas, L929 adipose-derived cells, immortalized BHK-21 cells, and the murine mammary derived JC cells. Additionally, in vivo VSV23 infection results in JC tumor destruction and induces enhanced memory responses against tumor cells.
KW - IL-23
KW - Oncolysis
KW - Oncolytic activity
KW - Tumor cells
KW - Vesicular stomatitis virus
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M3 - Article
AN - SCOPUS:77953460794
SN - 1179-139X
VL - 2
SP - 63
EP - 72
JO - International Journal of Interferon, Cytokine and Mediator Research
JF - International Journal of Interferon, Cytokine and Mediator Research
IS - 1
ER -