Talking Virotherapy with Oncolytics Biotech CEO Brad Thompson

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Some viruses cause cancer. Others kill it.

Yesterday, the US Food and Drug Administration granted Orphan Drug Designation to Alberta-based Oncolytics Biotech for their lead cancer treatment candidate, Reolysin, for the treatment of ovarian cancer. Reolysin is a modified version of a virus known as reovirus. Reovirus is an acronym that stands for Respiratory Enteric Orphan Virus.

Reolysin is one drug in an emerging field known as oncolytic virotherapy, the use of replication competent viruses to selectively seek out and kill cancer cells.

To learn more about Reolysin and virotherapy, I talked with Chairman, President and CEO of Oncolytics Biotech, Dr. Brad Thompson.

RB: What is Reolysin?

Thompson: Reolysin is a modified form of the reovirus, a very common virus that attaches to the lining of our lungs and bowel. Reovirus is pan-mammalian; humans get it, dogs get it, squirrels get it, deer get it. You can find reovirus in almost all municipal tap water. By the time most people reach adulthood they have been exposed to the virus.

Most people associate viruses with illness. What illness or symptoms does reovirus cause?

Reovirus doesn't cause symptoms or illness in humans. In fact, the vast majority of viruses don't cause any illness. It's a fairly short list that actually do. I would expect between 85 to 90 percent of known viruses do not cause illness or symptoms in humans when infected.

How does Reolysin work?

The reovirus hitchhikes on most blood cell types and becomes invisible to the immune system. All viruses have techniques either to hide themselves from the immune system or to suppress a response from that system. So when you inject Reolysin into a patient, it attaches itself to almost any blood cell except red blood cells, and those cells deliver it to the tumor.

Once inside the tumor cell, the virus begins to replicate, or make copies of itself. There is nothing inside the cancer cell that can stop the virus from replicating, so it replicates until there is so much virus that the cell explodes.

Where does this selectivity come from? Why doesn't the virus replicate and kill healthy cells?

In healthy cells, the reovirus is unable to replicate. There is a select group of genetic defects in tumor cells that allows the virus to grow.

So the human immune system has no defenses against reovirus?

It does but it can't neutralize it. We spent four or five years looking into whether, if you take this modified reovirus and put it into the human body, is the immune system going to block it? It turns out there is a huge, massive immune response to this virus, but we also found that it was still finding its way to tumors by masking itself and riding along the surface of blood cells.

Since Reolysin requires the likes of lymphocytes to carry it to the tumor, does this mean that immunocompromised patients aren't good candidates for virotherapy?

No, it doesn't mean that. [Note: Here Thompson, in a very politely Canadian way, tried to point out to me that the immune system is extremely complex and not simply related to lymphocyte count, which is the incorrect conclusion that was implicit in my question. For the sake of brevity I'm omitting that part…]

There are vertical and horizontal deficits in the immune system. If your entire immune system were to be suppressed, that would be horizontal—it shuts everything down. Very few things push everything in your immune system down. It's very rare. Typically people have vertical deficits; some are more susceptible to bacterial infections, others to viral infections. It's in your genetic make-up and everyone's immune systems are different.

The people that we're treating have often been treated with other agents that beat up their immune systems so their immune systems are a bit wonky to begin with. By definition if you have cancer, your immune system is defective. You've had cancer, I've had cancer many times, it has never turned into a true manifestation of the disease because the immune system is normally very good at taking care of it before it gets that far.

Is virotherapy here to stay?

Yes. Well I mean I think so. And if you talk to anybody in this field, they will tell you that there is this sense that we're really, really close to something big.

So viruses aren't so bad after all. It's a question of, which virus.

Up to a quarter of your genetic material came from viruses infecting your ancestors, dating back hundreds of millions of years. It's one of the driving elements of evolution—viruses introducing new genetic material.


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