title: Propagation, purification, and in vivo testing of oncolytic vesicular stomatitis virus strains.
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.
authors.affiliation: Ottawa Hospital Research Institute and University of Ottawa, Ottawa, ON, Canada.
authors.forename: Jean-Simon
authors.initials: JS
authors.lastname: Diallo
authors.forename: Markus
authors.initials: M
authors.lastname: Vähä-Koskela
authors.forename: Fabrice
authors.initials: F
authors.lastname: Le Boeuf
authors.forename: John
authors.initials: J
authors.lastname: Bell
mesh_terms: D000818:Animals; D005822:Genetic Vectors; D006801:Humans; D008562:Membrane Glycoproteins / Q000097:blood / Q000276:immunology; D051379:Mice; D050505:Mutant Proteins / Q000235:genetics; D009374:Neoplasms, Experimental / Q000628:therapy; D050130:Oncolytic Virotherapy / Q000379:methods*; D015398:Signal Transduction / Q000235:genetics; D018116:Vesiculovirus / Q000235:genetics / Q000254:growth & development* / Q000302:isolation & purification*; D014776:Virus Cultivation / Q000379:methods*; D014779:Virus Replication / Q000235:genetics
chemical_list: D008562:Membrane Glycoproteins; D050505:Mutant Proteins