Researchers have successfully engineered human adenovirus 5, which causes common cold symptoms, to evade the immune system and successfully infect tumor cells. The work is a significant advancement in viral gene therapy for the treatment of aggressive tumors. Adenovirus is an ideal vehicle for gene delivery since it can be engineered to have its replication mechanism removed rendering the virus harmless, meaning it cannot cause infection. In addition, the adenovirus genome is too large to integrate with human chromosomes. A paper describing the research has been published in Nature Communications.
Image: The adenovirus (left) camouflages itself from the immune system thanks to its protective coat (right). Image courtesy of the University of Zurich.
Two major modifications were made to the virus that enable it to survive and specifically target tumor cells. The first is an artificial protein-based shield that wraps around the hexon shell protein of the virus. The protein shield allows the virus to be invisible to immune cells and to avoid degradation by the liver, which would naturally remove unmodified viruses. The second modification includes adaptor molecules that attach to the virus and recognize cell surface receptors expressed by tumor cells. In this study, the team tested adaptors for HER2 and EGFR and found that only the viruses that had adaptors specific for these receptors were able to identify and infect tumor cells displaying these receptors.
The next steps are to develop therapies for different types of cancer using these adenoviral gene delivery systems or “gene shuttles.” Researchers are hopeful that this new viral-based therapy can overcome drug resistance which is recognized to be one of the biggest obstacles in cancer medicine efficacy. Biochemist Andreas Plueckthun, leader of the study and professor at the Department of Biochemistry at the University of Zurich, is optimistic: “With this gene shuttle, we have opened up many avenues to treat aggressive cancers in the future, since we can make the body itself produce a whole cocktail of therapeutics directly in the tumor."