Mutant adenovirus quells pancreatic cancer in mice

Last Updated: 2018-02-14

By David Douglas

NEW YORK (Reuters Health) - A novel oncolytic adenoviral mutant, Ad5-3Delta-A20T, helps avoid resistance and can effectively target and eliminate pancreatic cancer in vitro and in a mouse model, researchers have found.

"We've shown for the first time that pancreatic cancers can be specifically targeted with a modified version of the common flu virus," Dr. Stella Man of Queen Mary University of London said in a statement.

Metastatic pancreatic ductal adenocarcinomas (PDACs) are incurable due to the rapid development of resistance, Dr. Man and colleagues note in Molecular Cancer Therapeutics, online January 24. However, they add, unlike normal tissue many PDACs express alpha beta 6 integrins.

The team thus modified a previously developed oncolytic adenovirus to selectively target these integrins and to facilitate systemic delivery. The resultant virus Ad5-3Delta-A20T replicated in and killed cultured PDAC cells - in xenografts in vivo, and in three-dimensional coculture models with pancreatic stellate cells.

The agent also retained all viral functions necessary for propagation in the presence of the chemotherapy drug, gemcitabine.

"The new virus," Dr. Man added, "specifically infects and kills pancreatic cancer cells, causing few side effects in nearby healthy tissue. Not only is our targeting strategy both selective and effective, but we have now further engineered the virus so that it can be delivered in the bloodstream to reach cancer cells that have spread throughout the body."

However, in email comments to Reuters Health, senior author Dr. Gunnel Hallden, also of Queen Mary, cautioned that, "As with all potential new therapies, advancement towards clinical trials will require more studies."

"Together with our collaborators in Dr. Alan Parker's team, who engineered the novel adenovirus mutant in this study, we may further optimize the virus to enhance anti-tumor immune responses and prolong circulatory half-life to improve on targeting of metastatic lesions," Dr. Hallden said.

With funding in place and early phase trials to determine safety and tumor targeting initiated, she concluded, "Final development of the new mutant(s) for PDAC patients could become a reality within a 10-year time-frame."

SOURCE: http://bit.ly/2BXRWeB

Mol Cancer Ther 2018.