Amanda Simkhovich

Melanoma is a fast metastasizing skin cancer. Rates of melanoma are increasing with limited treatment options. Oncolytic Adenoviruses (OAds) bind directly to tumor cells, replicate, infect, and kill the cell while delivering tumor-specific therapeutic transgenes. Murine cells do not permit the replication of human OAds, which affects the analysis of biodistribution and adenovirus-mediated toxicity. Syrian hamsters have been reported to permit replication of human adenovirus. The goal of this study was to establish a hamster model for melanoma. In order to determine the replication ability of human OAd in hamster melanoma cells in vitro, a crystal violet cell viability assay was performed. CCL49 and ABC1 hamster melanoma cell lines were plated onto 4 12 well plates and incubated for 24 hours. After, the cells were infected with 3 OAds equipped with either wild fiber Ad5 (Ad-5-Wt) or RGD fiber (RGD-Wt). Post-infection, the plates were incubated for 3, 9, 7, and 12 days. The cells were stained and analyzed for cell viability. The data showed that the OAd equipped with RGD fiber (RGD-Wt) was able to best replicate within and kill the cells. These data also confirmed that the Ad5/Ad3 fiber modification is not optimal for hamster cell lines. Therefore, the RGD-based fiber modification has to be employed in rodent models to investigate the effectiveness and specificity of OAds. We are currently developing the in vivo hamster models of melanoma in order to evaluate the specificity and biodistribution of our vectors in immunocompetent models.