Forward Thinking Cancer Therapy to Go Viral?

There’s an ancient proverb about the uniting of two opposing forces against a third opponent that says, “The enemy of my enemy is my friend.”

The same could be said of the field of oncolytic virus research where scientists have been working to turn viruses that would otherwise be harmful to humans into specialized treatments that work with the immune system to target and destroy cancer cells.

The concept of using viruses to treat cancer is not new, but the field may be reaching a critical turning point, according to Robert Martuza, MD, former MGH Chief of Neurosurgery, and Nino Choicca, MD, PhD, Neurosurgeon in Chief and Chair of the BWH Neurosurgery Service.

Following decades of research into this innovative treatment strategy, the first viral-based therapeutic for patients with cancer was approved by the FDA in 2015. Martuza and Choicca hope this will pave the way for the rapid development of more therapies for patients as they continue to work on ways to improve the effectiveness of the treatment.

“We have one product,” Chiocca says. “The question is if this is going to be a one-off or if additional oncolytic viruses will be approved and used for different cancers as well.”

For Martuza, who is an active researcher at MGH, the concept of using viral treatments for cancer began in the early 1990s when he was browsing through magazine articles on physics and his mind caught on to the concept of parallels.

“Physicists have this idea of symmetries,” he explains. “If you find an up quark, you can predict that there is going to be a down quark. If you find a positively charged particle, you can predict there is going to be a similar negatively charged particle.”

Martuza then considered how symmetries work in cancer. “If you think about it, what can cause cancer are the same things we use to cure cancer,” he says. “Chemical exposure can cause cancer, but chemicals in the form of chemotherapy can cure it. Radiation exposure can cause cancer, but one of the things we do when people get cancer is give them radiation.”

He then made a third connection. “Viruses also cause cancer. They cause lymphoma and leukemia, and the human papillomavirus (HPV) causes cervical cancer. But no one was looking at viruses to cure cancer.”

“So, if you have two tumors and inject one, the virus will kill the cancer cells on one side and the immune response will kill the second.”

Researchers are now looking toward a third evolution in treatment—putting foreign cancer antigens (molecules that stimulate an immune response) directly into the virus or using viral therapy in conjunction with checkpoint inhibitors.

Tumor cells have “checkpoints” on them that essentially render the cells invisible to the body’s immune system, allowing the cancer to grow unchecked by the body’s natural defenses.

By simultaneously priming the immune system to target cancer cells and blocking the checkpoints that would otherwise hide the cancer cells, it may be possible to cure tumors that are incurable using either treatment alone, Martuza says. It should be noted that other Partners faculty have also developed highly promising technology that inhibits those checkpoints that have been previously featured in this newsletter.

While viral-based treatments have demonstrated some success, they could always work better, Chiocca acknowledges. “We would only say it works great once we’ve cured cancer, and that’s a long way away. I suspect as we do more of this we’ll find there are mechanisms by which tumors are able to evade this as well. So, there is always resistance to everything.”