Researchers in the College of Medicine are working to genetically modify poxviruses that would target and destroy tumors. Not only could the results reap a new weapon against an evasive and brutal disease, in the long term they could lead to the ability to customize viruses for a patient's immune system.
"There certainly may come a day where we're able to predict which virus will work best for patients by looking at how they are immune deficient," said Joanna Shisler, College of Medicine faculty member professor of microbiology at the University of Illinois at UrbanaChampaign. She is collaborating with other Illinois faculty, including Edward Roy, College of Medicine researcher and professor of pathology, and Amy MacNeill, professor of veterinary medicine.
Shisler's work provides the foundation for the research, focusing on the underlying biology of a virus. As viruses have evolved, they have developed sophisticated mechanisms for taking over a cell and evading immune response. In particular, she is studying NFkappa B, a cellular protein that is also the master regulator of a cell's immune response. When a virus invades a cell, it uses its own immunoevasion proteins to switch off NF-kappa B, preventing the production of proinflammatory molecules and enhancing virus survival.
By better understanding the immunoevasion response in viruses, researchers hope to use this information to their advantage. Specifically, researchers are working to remove some of these immunoevasion genes to create an attenuated virus that would be a safer vector for cancer therapy.
"Viruses are giving us clues as to what they perceive as a target," Shisler says. "There's a lot of rich information to be learned about how they neutralize immune response."
Roy and MacNeill are reaching across disciplines to use the knowledge gained from basic science to develop new poxvirus-based vaccines. They are currently working with the myxoma virus, which selectively infects and kills tumor cells, but not healthy cells. For this reason, they are called "oncolytic" viruses. The virus attacks in two ways: It can directly kill the tumor cells it infects, but also has been engineered to stimulate the immune system to attack tumor cells that escape the first offensive. Roy and MacNeill collaborate to optimize a myxoma virus that will kill brain tumors in laboratory mice. In the next phase of research, MacNeill will study oncolytic poxviruses in dogs with cancer, observing the effects of myxoma virus infection in naturally developing tumors. Since dogs, like people, can develop cancer from environmental causes, the research could give great insight into how humans respond to the treatment.
There are inherent risks with this approach. Viruses could mutate and become more virulent, a devastating side effect for a cancer patient with an already compromised immune system. Also, if not programmed properly, the immune system could destroy the viruses before it ever reaches the cancer cell. They could also lose their potency.
Researchers are working to mitigate potential risks in part by learning how poxviruses evade immune responses. For example, the genetic alterations to the myxoma virus that stimulate an anti-tumor response also make the virus less virulent. In addition to creating a new cancer-fighting tool, Shisler says a greater understanding of viruses will reveal new insights into cell biology. "Some of the most important discoveries related to cell biology have been made by studying viruses," she said. "They can actually teach us about the largest functions of biology."