Greg Delgoffe, PhD @delgoffelab of @PittTweet explains how the dual-function virus designed to killing tumors is affecting clinicians today.
Viruses designed to kill cancer cells are already used to treat one skin cancer and are commonly studied in other cancers.
A new study shows that oncolytic viruses known as viruses can be enhanced further to improve the body's immune response to tumors. The researchers found that this new type of oncolytic virus can simultaneously kill the cancer cells and provide tumor immune cells with a hormone that they need to perform their own cell killing functions.
The dual-function virus was significantly more active in shrinking and removing tumors in mice with melanoma tumors than a regular oncolytic virus.
The findings of the study were published in Immunity on 17 September.
“The new thing here is that this virus has been engineered to relieve immunosuppression” in addition to killing tumor cells outright, explained Phillip Daschner, program director in NCI’s Division of Cancer Biology, who was not involved with the study. “It’s an idea that may be quickly translated to use in patients.”
Shut Down by a Toxic Environment
Oncolytic viruses kill cancer cells, but studies also show they can increase the ability of the immune system to recognize and kill a tumor.
Specifically, the viruses enter tumor cells and multiply them, breaking up the cells. When this breakdown happens, cancer cell proteins that the immune system–known as tumor antigens-recognizes are released into the bloodstream. This can lead to the incorporation of T cells into a tumor and can even lead to metastatic cancer elsewhere in the body.
But getting T cells to reach and enter a tumor is only part of the challenge, explained Greg Delgoffe, Ph.D., of the University of Pittsburgh Medical Center, who led the new study. “The tumor environment by its own nature is toxic,” he said. “When T cells get in, they experience a harsh, low-oxygen, desert-like landscape.” This environment can render immune cells unable to function.
Dr. Delgoffe's lab tested an oncolytic virus (an engineered variant of the virus Vaccinia) to better understand how cancer-immune cell interactions alter following a viral tumor infection. They found that their virus was able to lead to a significant number of T cells entering tumors when injected into tumors in the mice.
The newly arrived T cells seemed healthy and vigorous, according to the researchers. Yet T cells ' ability to kill can fade and become soft spectators with reduced ability to damage cancer cells — a phenomenon also known as fatigue.