Targeting Human Glioblastoma Cells: Comparison of Nine Viruses with Oncolytic Potential

Abstract

Brain tumors classified as glioblastomas have proven refractory to treatment and generally result in death within a year of diagnosis. We used seven in vitro tests and one in vivo trial to compare the efficacy of nine different viruses for targeting human glioblastoma. Green fluorescent protein (GFP)-expressing vesicular stomatitis (VSV), Sindbis virus, pseudorabies virus (PRV), adeno-associated virus (AAV), and minute virus of mice i-strain (MVMi) and MVMp all infected glioblastoma cells. Mouse and human cytomegalovirus, and simian virus 40 showed only low levels of infection or GFP expression. VSV and Sindbis virus showed strong cytolytic actions and high rates of replication and spread, leading to an elimination of glioblastoma. PRV and both MVM strains generated more modest lytic effects and replication capacity. VSV showed a similar oncolytic profile on U-87 MG and M059J glioblastoma. In contrast, Sindbis virus showed strong preference for U-87 MG, whereas MVMi and MVMp preferred M059J. Sindbis virus and both MVM strains showed highly tumor-selective actions in glioblastoma plus fibroblast coculture. VSV and Sindbis virus were serially passaged on glioblastoma cells; we isolated a variant, VSV-rp30, that had increased selectivity and lytic capacity in glioblastoma cells. VSV and Sindbis virus were very effective at replicating, spreading within, and selectively killing human glioblastoma in an in vivo mouse model, whereas PRV and AAV remained at the injection site with minimal spread. Together, these data suggest that four (VSV, Sindbis virus, MVMi, and MVMp) of the nine viruses studied merit further analysis for potential therapeutic actions on glioblastoma.

Oncolytic Efficacy of Recombinant Vesicular Stomatitis Virus and Myxoma Virus in Experimental Models of Rhabdoid Tumors

“…Thus, MV could be a useful therapeutic agent in at least a subset of rhabdoid tumor. Cui et al (12) Despite a rapidly increasing number of studies examining the utility of oncolytic viruses against many cancers, there have been few comparisons of the efficacy or toxicity of multiple oncolytic viruses in a single model (19,43). Here, we have directly compared the oncolytic efficacy of MV and VSV…”

Evaluation of cancer virotherapy with attenuated replicative Semliki forest virus in different rodent tumor models

“…Thus, it is likely that the type I IFN response, perhaps in concert with other components of the innate immune response, is one of the major hurdles against successful virotherapy. 30 In nude mice, also virus-specific IgM plays an important role in controlling the infection, and although antibodies alone are unable to clear the virus from the CNS, they may remove it from the subcutaneous tumors. 21,22 It has been shown that the vasculature in many solid tumors is leaky for serum protein components, including immunoglobulins.…”

Glioma-Parvovirus Interactions: Molecular Insights and Therapeutic Potential

“…The first report about cytotoxicity of a parvovirus against transformed neural cells was on the MVMp and MVMi infection of rat C6 glioma and several human glioblastoma and astrocytoma cells (Rubio et al 2001). The MVM infections of human cells were cytotoxic but poorly productive, as found some years afterwards by an independent study (Wollmann et al 2005). Although a parallel study with the MVM and H-1 viruses has not being carefully addressed, several subsequent reports suggested that H-1 is a more powerful oncolytic agent against human glioblastoma, regarding the levels of both cytotoxicity and virus yield in culture (Herrero et al 2004;Di Piazza et al 2007).…”