Oncolytic Viruses Put Immune System on High Alert

An oncolytic virus that is being tested in clinical trials shows potential as a cancer vaccine, according to a study published by Cancer Research.

In addition to directly killing cancer cells, the authors discovered that the virus can make the immune system aware of a tumor, resulting in a widespread immune response. The effect of this novel approach reached far passed the region infected with the virus, according to the study authors.

Notably, the study outlines how oncolytic viruses are able to attack tumors and how it works with the immune system to neutralize cancer cells.

The results suggest that the oncolytic virus could compliment checkpoint inhibitors and boost the immune system attack, which may be useful for drug-resistant disease, according to the authors.

The potential of viruses to launch an attack against cancer has generated much interest over the past few decades; however, there is still much unknown about how viral therapies can kill cancer cells and how to optimize this action.

Under different circumstances, viruses appear to attack cancer cells in various ways, including infecting the cells, releasing tumor proteins that elicit an immune response, and inhibiting the blood supply that tumors need to survive, according to the authors.

The researchers specifically explored Pexa-Vac, which is currently being investigated in clinical trials for liver and colorectal cancers. The investigational vaccine is based on the vaccinia cowpox virus. It infects only cancer cells and boosts immune activity, according to the authors.

“This got my attention in part because this virus could be given systemically by intravenous injection, in contrast to most oncolytic viruses that are injected into the tumor itself, which obviously limits their therapeutic potential against cancers that are inaccessible or have spread to multiple sites in the body,” Dr McDonald said.

In the study, mouse models of neuroendocrine pancreatic cancer received an intravenous infusion of the vaccine. The researchers discovered that the virus infected the blood vessels within a tumor but did not affect healthy organs. The initial infection caused the vessels to leak and leave the tumor vulnerable, according to the study.

The oncolytic virus was found to infect and kill a small number of cancer cells directly; however, within 5 days, the rest of the tumor cells were killed due to the strong immune reaction elicited by the initial attack, according to the study.

“At first small spots of the tumor were infected, but then most of the tumor started to die,” Dr McDonald said. “We were able to show that while only about 5% of cells were infected by the virus, the number of cells that were killed was more than 10 times higher. As far as I know, no one has ever done this kind of analysis.”

The study showed the viral infection that killed some cancer cells directly sparked an immune system attack against the rest of the tumor.

Further, a combination of the virus and sunitinib—a blood vessel growth inhibitor that increases immune function—resulted in a significantly greater tumor-killing effect, according to the study. The addition of sunitinib caused the immune system to go into overdrive to detect tumor proteins related to viral infection.

These findings suggest that a combination of oncolytic viruses with checkpoint inhibitors may be extremely lethal to cancer, according to the authors.

“The question with immunotherapy has always been—why doesn’t the immune system naturally detect and attack cancer cells?” Dr McDonald said. “It seems like these viruses are like setting off a bomb that jars the immune system. The infection releases tumor antigens in a way that jump-starts the immune response.”