Turning viruses against cancer

Julia Davydova

What do the common cold, sodium, and pigs have in common?

If research led by Masons-funded faculty member Julia Davydova, M.D., Ph.D., is successful, together the three may be the key to fighting pancreatic cancer.

Common cold for the common good?

Davydova is part of a growing cadre of University investigators who are at the forefront of using viruses to stop cancer. Called “oncolytic viruses,” the therapies work by delivering certain genes and proteins deep into the body to stop the spread of cancer.

To deliver a knockout punch to pancreatic cancer, Davydova’s lab has produced an oncolytic adenovirus—derived from the virus that causes the common cold—that can deliver a therapy called NIS (sodium iodide symporter).

The adenovirus “doesn’t integrate into the genome, doesn’t cause mutations, and, since it’s the common cold virus, is not associated with any severe disease,” says Davydova. Moreover, NIS, which occurs naturally in the thyroid, has been used for decades to detect and kill thyroid cancer cells. It is arguably why most people survive thyroid cancer.

After completing a major preclinical study on the impact of their treatment in human tissue, Davydova’s team has achieved “amazingly good results” and is now working to patent-protect this unique therapy.

Moving toward clinical trials—of pigs and people

The next big step for Davydova and her team is to prove that their adenovirus therapy is safe and effective in people. But first, they must find a reliable animal model for testing its impact.

“We are so eager to start clinical trials, but we don’t have a good in vivo model for testing toxicity and efficacy,” says Davydova. “The problem is that human adenovirus is very species-specific and tends to replicate only in human tissue. This means we can’t use the traditional approach of studying it in mice.”

To overcome this obstacle, Davydova and her colleagues are collaborating with faculty across the U and a local gene editing company called Recombinetics to create a swine model of pancreatic cancer. Because pigs are genetically and physiologically similar to people, they are already used for research on a variety of diseases. Most important for Davydova’s team, their tissue allows for the replication of human adenovirus.

But also like people, pigs develop cancer only as they age. That’s why Davydova and her colleagues at Recombinetics are working to create a pig that can develop cancer at any point during its life. With Masonic support, they have successfully engineered swine fibroblasts that carry human pancreatic cancer mutations. They’re now applying for federal grant support to complete the model. If successful, their work would mark the first time a pig model has been developed for the study of pancreatic cancer.

A unique environment

Davydova believes there are few places in the world where such out-of-the-box research can happen.

The team involved in her study stretches across the U and beyond, encompassing surgeons, geneticists, virologists, radiologists, and, ultimately, philanthropists. In addition to Davydova, the group is led by some of the brightest minds in cancer research, including Perry Hackett, Ph.D., genome engineering expert and professor of genetics, cell biology, and development at the U, and Adrienne Watson, Ph.D., senior research scientist at Recombinetics.

This level of collaboration and expertise are part of what makes cancer research at the U and its Masonic Cancer Center special.

“We have a unique environment here at the U that has made this project successful so far,” says Davydova. “This includes strong partnerships with local biotech companies, gene editing technology invented at the U, one of the best magnetic resonance centers in the world, strong surgery and radiology departments, experimental surgical services, and donors who believe in and appreciate what we’re trying to do.”