Bacteria Enhance the Effectiveness of Cancer-Killing Viruses

The virus exhibits significant promise in treating various cancer types, yet immune responses limit its use primarily to tumors located near the skin’s surface. Current research demonstrates that employing genetically modified bacteria to envelop these viruses may mitigate this issue, effectively slowing the advancement of aggressive tumors in mouse models.

Several treatments utilizing oncolytic viruses have received global approval for targeting cancers of the skin, brain, and head and neck. These methods often involve injecting engineered viruses directly into tumors, which then disperse and destroy cancer cells.

However, targeting deeper tumors necessitates injecting the virus into the bloodstream, where the immune system swiftly eradicates it before it can reach the desired site.

To circumvent this challenge, Zachary Singer and his team at Columbia University, New York, are using genetically modified Salmonella Typhimurium bacteria that do not elicit a strong immune response. These bacteria have been engineered to harbor the genome of Seneca virus A, a virus shown to effectively eliminate human cancer cells in laboratory and animal studies.

“We are adopting a Trojan horse strategy where bacteria conceal the virus [from the immune system],” remarks Singer. These bacteria are designed to infiltrate cancer cells and release copies of the viral genome upon entry.

To test their hypothesis, researchers induced neurotumors on mice’s backs. A week later, they administered the bacteria carrying the virus. This was referred to as a capsid, which entered about half the mouse’s blood. The other group received Seneca virus A without the bacteria.

Within a day, they noted that fluorescent-tagged capsids had concentrated within the tumor, a reaction that typically dampens the immune response. In contrast, capsids remaining in the bloodstream or reaching healthy tissue were swiftly eliminated by the immune system, according to Singer.

On average, tumors in the Seneca virus A-only group reached their maximum size in 11 days, necessitating euthanasia for ethical reasons. Conversely, tumors in the capsid group took 21 days to reach the same size, with no mice experiencing notable side effects.

“The data appears truly remarkable,” states Guy Simpson from the University of Surrey, UK. The findings have shown effectiveness against rapidly growing tumors, particularly those arising from neurons, but he suggests it may be even more beneficial for slower-growing tumors.

In a separate aspect of the experiment, the researchers discovered that the capsid entirely eradicated human lung tumors implanted on mouse backs, yet they did not include controls that received Seneca virus A on its own.

Before human trials, additional studies on mice and non-human primates should assess its efficacy against a broader spectrum of tumors, including pancreatic cancer, which has notoriously low survival rates, advises Simpson.