Mining the Adenovirus Virome for Oncolytics Against Multiple Solid Tumor Types

Although there are 55 serotypes of adenovirus that infect humans, Ad5 is the most widely studied due to the availability of commercial kits for its genetic manipulation. In fact, engineered adenovirus serotype 5 is currently being used in all of the 87 global clinical trials utilizing adenovirus for the treatment of cancer. Unfortunately, Ad5 is one of the most seroprevalent serotypes, meaning that this virus has to confront additional immunological barriers to be effective in Ad5-immune patients. In this work, we compare Ad5 to 13 other adenoviral serotypes from species B, C, D, and E for oncolytic potential in both immunodeficient mouse and immunocompetent hamster models. Our results indicate that species D adenoviruses are not effective oncolytics against most solid tumors. Conversely, lower seroprevalence Ad6 and Ad11 hade anti-cancer activity comparable to Ad5. This work strongly supports the consideration of Ad6-based oncolytic therapies for the treatment of breast, ovarian, kidney, and liver tumors.