Abstract
Oncolytic viruses are self-amplifying therapeutics that specifically replicate in and kill cancer cells. We have previously shown that vesicular stomatitis virus (VSV) can be used as an oncolytic virus. A strain of VSV harboring a mutation in the M protein (VSVΔ51) was found to exhibit enhanced tumor selectivity over its wild-type counterpart due to its inability to overcome antiviral programs in normal cells and due to the frequent defects in antiviral signaling pathways observed in the majority of tumors. VSVΔ51 can harbor transgenes, is easily propagated and purified to high titers, and shows potent oncolytic activity in several mouse models, including syngeneic CT26-lacZ subcutaneous colon carcinoma models. However, VSV-neutralizing antibodies targeting mainly the VSV-G surface glycoprotein arise within 3–5 days following the initial dose. This should be considered for strategies aiming at increasing the effectiveness of VSV through delivery of additional doses of virus or aiming to prolong VSV replication in vivo.
This is a preview of subscription content, log in via an institution to check access.
Access this chapter
Tax calculation will be finalised at checkout
Purchases are for personal use only
References
Rose, J., Whitt, M. (2001) Rhabdoviridae: The viruses and Their Replication, 4th ed., Lippincott Williams and Wilkins, New York.
Lichty, B. D., Power, A. T., Stojdl, D. F., and Bell, J. C. (2004) Vesicular stomatitis virus: re-inventing the bullet. Trends Mol Med10, 210–6.
Stojdl, D. F., Lichty, B., Knowles, S., Marius, R., Atkins, H., Sonenberg, N., and Bell, J. C. (2000) Exploiting tumor-specific defects in the interferon pathway with a previously unknown oncolytic virus. Nat Med6, 821–5.
Stojdl, D. F., Lichty, B. D., tenOever, B. R., Paterson, J. M., Power, A. T., Knowles, S., Marius, R., Reynard, J., Poliquin, L., Atkins, H., Brown, E. G., Durbin, R. K., Durbin, J. E., Hiscott, J., and Bell, J. C. (2003) VSV strains with defects in their ability to shutdown innate immunity are potent systemic anti-cancer agents. Cancer Cell4, 263–75.
Obuchi, M., Fernandez, M., and Barber, G. N. (2003) Development of recombinant vesicular stomatitis viruses that exploit defects in host defense to augment specific oncolytic activity. J Virol77, 8843–56.
Segura, M. M., Garnier, A., and Kamen, A. (2006) Purification and characterization of retrovirus vector particles by rate zonal ultracentrifugation. J Virol Methods133, 82–91.
Cantin, R., Diou, J., Belanger, D., Tremblay, A. M., and Gilbert, C. (2008) Discrimination between exosomes and HIV-1: purification of both vesicles from cell-free supernatants. J Immunol Methods338, 21–30.
Le Boeuf, F., Diallo, J. S., McCart, J. A., Thorne, S., Falls, T., Stanford, M., Kanji, F., Auer, R., Brown, C. W., Lichty, B. D., Parato, K., Atkins, H., Kirn, D., and Bell, J. C. (2010) Synergistic Interaction Between Oncolytic Viruses Augments Tumor Killing. Mol Ther18 (5), 888–95.
Nguyen, T. L., Abdelbary, H., Arguello, M., Breitbach, C., Leveille, S., Diallo, J. S., Yasmeen, A., Bismar, T. A., Kirn, D., Falls, T., Snoulten, V. E., Vanderhyden, B. C., Werier, J., Atkins, H., Vaha-Koskela, M. J., Stojdl, D. F., Bell, J. C., and Hiscott, J. (2008) Chemical targeting of the innate antiviral response by histone deacetylase inhibitors renders refractory cancers sensitive to viral oncolysis. Proc Natl Acad Sci USA105, 14981–6.
Parato, K. A., Senger, D., Forsyth, P. A., and Bell, J. C. (2005) Recent progress in the battle between oncolytic viruses and tumours. Nat Rev Cancer5, 965–76.
Stanford, M. M., Breitbach, C. J., Bell, J. C., and McFadden, G. (2008) Innate immunity, tumor microenvironment and oncolytic virus therapy: friends or foes? Curr Opin Mol Ther 10, 32–7.
Ikeda, K., Ichikawa, T., Wakimoto, H., Silver, J. S., Deisboeck, T. S., Finkelstein, D., Harsh, G. R., Louis, D. N., Bartus, R. T., Hochberg, F. H., and Chiocca, E. A. (1999) Oncolytic virus therapy of multiple tumors in the brain requires suppression of innate and elicited antiviral responses. Nat Med 5, 881–7.
Acknowledgments
This work was supported in part by the Canadian Institutes of Health Research, the Ontario Institute for Cancer research, and the Fonds de Recherche en Santé du Québec.
Author information
Authors and Affiliations
Corresponding author
Editor information
Editors and Affiliations
Rights and permissions
Copyright information
© 2012 Springer Science+Business Media, LLC
About this protocol
Cite this protocol
Diallo, JS., Vähä-Koskela, M., Le Boeuf, F., Bell, J. (2012). Propagation, Purification, and In Vivo Testing of Oncolytic Vesicular Stomatitis Virus Strains. In: Kirn, D., Liu, TC., Thorne, S. (eds) Oncolytic Viruses. Methods in Molecular Biology, vol 797. Humana, Totowa, NJ. https://doi.org/10.1007/978-1-61779-340-0_10
Download citation
DOI: https://doi.org/10.1007/978-1-61779-340-0_10
Published:
Publisher Name: Humana, Totowa, NJ
Print ISBN: 978-1-61779-339-4
Online ISBN: 978-1-61779-340-0
eBook Packages: Springer Protocols