Using Viruses to Cure Cancer

Researchers at Arizona State University have reviewed a class of viruses that act to combat rather than cause cancer. They are known as oncolytic viruses. And they have a remarkable ability to target and destroy cancer cells, while leaving healthy cells untouched.

"The field of oncolytic virotherapy today is advancing rapidly as clinical trial data accumulates and regulatory approvals continue to accrue," says Grant McFadden in a press release issued by Arizona State University. McFadden is the director of the Biodesign Center for Immunotherapy, Vaccines and Virotherapy.

A paper is published in Cancers. It reviews oncolytic viruses, which are viruses that selectively target and kill cancer cells while sparing normal ones. And it explores how oncolytic viruses are emerging as key cancer treatment agents. Genetically engineered oncolytic viruses have been developed to work around the therapeutic limitations of naturally occurring ones.

The first clues that oncolytic viruses may exist in nature came over a century ago. Physicians noticed that some cancers appeared to regress in patients that also had infections.

Many oncolytic viruses can directly attack and kill cancer cells. But their primary strength may be their ability to alert an inactive or disabled immune system to the presence of cancer. Oncolytic viruses can be genetically re-engineered to sharpen their lethality to cancer cells, as well as their ability to stimulate the immune system.

The Arizona State University researchers worked with a promising rabbit virus with oncolytic properties. It is called myxoma virus. And it attacks and kills human cancer cells, while being completely harmless to non-cancerous cells.

Myxoma virus is an attractive candidate for oncolytic virotherapy because its large genome is amenable to improvements using genetic modification. Scientists may be able to enhance its ability to kill cancer and, at the same time, enhance its ability to trigger a stronger anti-cancer response from the immune system.

The researchers suggest that oncolytic virotherapy could be especially successful in combination with a form of cancer immunotherapy based on checkpoint inhibitors.

"When patients respond to checkpoint inhibitors, it's often like magic," McFadden says. "They can undergo massive tumor regression and long term, disease-free survival."

Cancers exploit proteins called checkpoint proteins to protect themselves from the immune system. And drugs based on checkpoint inhibitors can switch the immune system back on. However, this only works for a minority of cancer patients.

"New approaches like immune checkpoint inhibitors are very effective in reducing the tumor burden and improving survival, but it works only in a small number of patients - only 10-20%," cautions researcher Masmudur Rahman.

The researchers suggest that the majority of patients never develop an immune response to cancers, leaving nothing for the checkpoint inhibitor to restart. Here is where oncolytic virotherapy can boost cancer immunotherapy based on checkpoint inhibitors.

"We believe that if you get an infection going in the tumor bed, you can generate a new kind of immune response to both the tumor and the virus at the same time," McFadden concludes. "That new immune response, we hope, will result in more patients being susceptible to immunotherapies like checkpoint inhibitors."

Only four oncolytic viruses have been approved globally for clinical use. But others, including myxoma, are in pre-clinical trials. McFadden recently formed the company Oncomyx Therapeutics to further explore oncolytic virotherapy based on the myxoma virus.