Abstract 2724: Intravesical treatment with Vesicular Stomatitis virus decreases the size of bladder tumors without adversely affecting the health and well-being of immune-competent mice

Abstract

Abstract Recent studies have shown that wild-type Vesicular Stomatitis virus (VSV) and the Δ51M recombinant IFN-inducing mutant of wild-type VSV (AV3) have powerful oncolytic activity against bladder cancer cells in an immune-compromised bladder cancer model. The objective of the current study was to determine the safety and efficacy of the wild-type VSV and AV3 when intravesically administered to an immune-competent bladder cancer model. Using an established orthotopic bladder cancer model, 100 µL of 108 pfu mL−1 wild-type VSV, AV3, or UV-inactivated wild-type VSV (UVI) was instilled into the urinary bladders of female C3H mice. Half of the mice had normal, healthy bladders and were instilled with the oncolytic virus on day 0, 2, and 4. The remaining mice were given non-muscle invasive bladder tumors through the transurethral instillation of luciferase expressing MBT-2 mouse bladder carcinoma cells. On day 5 after initial tumor inoculation, tumor-bearing mice were imaged for bioluminescence and tumor size was quantified. On days 6, 8, and 10 after the initial tumor inoculation, tumor-bearing mice were randomized for treatment, and wild-type VSV, AV3, or UVI was instilled into each mouse. Levels of tumor bioluminescence (a correlate of tumor size), and body weight (a key variable of animal health and indicator of treatment toxicity) were monitored for 22 days. Following three consecutive intravesical treatments of an oncolytic virus, there were no differences in weight between the treated mice (wild-type VSV and AV3) and the control mice (UV-inactivated wild-type VSV), regardless of tumor presence. In addition, tumor bioluminescence in the AV3 treated mice was slightly decreased (30%) compared to the control mice, but not different from the wild-type VSV treated mice. These data correspond to in vitro data which show that wild-type VSV and AV3 are inhibitors of proliferation in MBT-2 mouse bladder carcinoma cells. In conclusion, our data strongly suggest that oncolytic viruses such as wild-type VSV and its attenuated form, AV3, can be used to treat superficial bladder cancer in immune-competent mice, without adversely affecting the health and well-being of the animal. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 102nd Annual Meeting of the American Association for Cancer Research; 2011 Apr 2-6; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2011;71(8 Suppl):Abstract nr 2724. doi:10.1158/1538-7445.AM2011-2724