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Newswise — Eric Bartee, PhD, is studying how to use viruses to fight cancer. The associate professor at The University of New Mexico Comprehensive Cancer Center has a $2 million grant to study how cells detect and rid themselves of viruses. He hopes to make oncolytic therapy, a form of immune therapy that uses viruses to alert the immune system to cancer, more effective.

“When it works,” Bartee says, “immunotherapy is unbelievably successful.”

Oncolytic therapy uses specific viruses to target cancer cells. These viruses are more likely to use cancer cells to copy themselves. Scientists can also alter viruses so that they are more likely to infect cancer cells.

“The basis of oncolytic therapy is having a virus which, for some reason or another, will infect cancer tissue but not normal tissue,” Bartee says.

All cells respond when a virus infects them. That cellular response alerts the immune system, the body’s natural and powerful protection against infected or cancerous cells.

Like an arsonist who disconnects the fire alarm before setting fire to a structure, each virus has evolved a way to keep the cell from responding to infection. When the cell cannot respond, it cannot alert the immune system.

Cancer cells, too, hide from the immune system by taking advantage of how the immune system works.

The immune system does not find and eliminate particular types of cells. Instead, immune cells — particularly T cells — distinguish only between cells that are part of the body and cells that are not. If a cell makes proteins that T cells don’t recognize, the T cells eliminate it.

Scientists have learned that if a virus replicates in tumor cells but does not prevent the cell from responding, then the cells’ response to infection draws T cells to the tumor. T cells clear not only the virus-infected cells but also the other tumor cells. And they can be very effective at removing all the tumor cells.

By harnessing a cell’s infection response to draw immune cells to tumors, oncolytic therapies have been able to dramatically reduce tumors in some people. But they don’t work for everyone. To make oncolytic therapy more effective, Bartee is studying how cancer cells evade the immune system.

The immune system has a shut-off process to protect the body’s cells. This process uses a protein called “programmed death 1” (PD1), which sits on a T cell’s surface. When T cells turn on to eliminate badly behaving cells, they create more PD1 along with a very toxic molecule called interferon.

Interferon induces cells to make a receptor on their surfaces called PDL1, which stands for “programmed death ligand 1.” Because the T cell must attach to the cell it is eliminating, the PDL1 receptors attach to the PD1 receptors on a T cell’s surface. When enough of these receptors attach, the T cell inactivates itself.

Cancer cells take advantage of this system by producing lots of PDL1 on their surfaces so when a T cell attaches to kill it, the cancer cell shuts down the T cell. Once shut off, T cells no longer eliminate cancer cells, and the remaining cancer cells can grow and multiply.

Many immune therapies keep T cells functioning by blocking PDL1. These therapies attach to the PDL1 receptor, preventing the PD1 receptor on the T cell from attaching. So, T cells never receive the message to inactivate.

But keeping T cells active is not enough, Bartee explains. To fight cancer, immune therapies – and therefore, oncolytic therapies – must do three things to work effectively. They must target cancer cells, increase the number of immune cells, and keep T cells activated.

Few immune therapies can do these three things at the same time. But Bartee thinks he may have created one that does. Bartee’s oncolytic therapy combines a version of a rabbit virus called myxoma with a type of drug called a TNF blocker.

In Bartee’s studies, about half the animals responded strongly to the myxoma virus alone: their tumors completely disappeared. The other half responded, but their tumors did not go away completely. However, when they were given a TNF blocker as well as the virus, their tumors completely disappeared.

TNF blockers reduce the inflammation caused by a molecule called tumor necrosis factor (TNF). These drugs are commonly used for conditions like rheumatoid arthritis or Crohn’s disease.

Myxoma virus infects rabbits by shutting down a rabbit cell’s infection response. But humans have different proteins, so myxoma does not shut down a human cell’s infection response. When myxoma infects human cells, the human T cells quickly activate and eliminate those infected cells.

“Myxoma is smallpox for rabbits. It is apathogenic in everything but rabbits,” Bartee says. “It is unbelievably lethal in European rabbits. It doesn’t do anything to people. I tell people, ‘You can drink it and won’t know it’s there.’”

But cancer cells do not respond to viral infection the way non-cancer cells do. So in cancer cells, myxoma surreptitiously enters and profusely replicates. When wandering immune cells detect the myxoma proteins in the cancer cells, they also find the cancer proteins and mobilize the immune system to eliminate the cancer cells, infected or not.

Bartee is now using his $2 million grant to study how the combination of myxoma virus and TNF blocker enables the immune system to eliminate cancer tumors in all the animals.

“The basic biology needs to be understood,” he says, “so that we don’t do something that ends up being backwards in a patient.”

The Grants

The National Cancer Institute and the National Institute of Allergy and Infectious Disease, both within the National Institutes of Health, supported the research reported in this publication under Award Numbers CA194090 (Eric Bartee, 2015-2021) and CA276134 (Eric Bartee, 2023 – 2028). The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health.

The University of New Mexico Comprehensive Cancer Center

The University of New Mexico Comprehensive Cancer Center is the Official Cancer Center of New Mexico and the only National Cancer Institute-designated Cancer Center in a 500-mile radius. Its 136 board-certified oncology specialty physicians include cancer surgeons in every specialty (abdominal, thoracic, bone and soft tissue, neurosurgery, genitourinary, gynecology, and head and neck cancers), adult and pediatric hematologists/medical oncologists, gynecologic oncologists, and radiation oncologists. They, along with more than 600 other cancer healthcare professionals (nurses, pharmacists, nutritionists, navigators, psychologists and social workers), provide treatment to 65% of New Mexico’s cancer patients from all across the state. And they partner with community health systems statewide to provide cancer care closer to home. In 2024 they treated more than 15,000 patients in almost 105,000 ambulatory clinic visits in addition to in-patient hospitalizations at UNM Hospital. A total of 2,075 patients participated in cancer clinical trials to study new cancer treatments that include tests of novel cancer prevention strategies and cancer genome sequencing. The more than 123 cancer research scientists affiliated with the UNM Cancer Center were awarded $38.3 million in federal and private grants and contracts for cancer research projects.

Website: unmhealth.org/cancer
UNM Cancer Center Clinic: 505-272-4946
UNM Cancer Center Community and Media Relations: 505-548-0927

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