Delivering Viruses To Try And Kill Tumors

Writing in the journal Nature, researchers report some early success using a systemically delivered, engineered virus to try and kill cancer tumors. University of Ottawa professor of medicine John Bell explains the study and the response of patients who received the virus.

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IRA FLATOW, host: This is SCIENCE FRIDAY. I'm Ira Flatow. We know viruses can cause disease, but can they also help cure it? Some cancer docs think so. Researchers have shown for years that infection with a virus, either by vaccination or by a naturally occurring infection, can cause some cancer tumors to regress, to get smaller.

But turning that observation into an actual treatment has not been very easy. One of the challenges, aside from getting the right virus, is getting that virus into the tumors. That's especially hard if a cancer has spread or metastasized, and you don't know where in the body the cancer might be.

But now researchers reporting in the journal Nature say there's been some progress. They've engineered a virus that they can give intravenously, and the virus seeks out those cancer tumors wherever they are in the body. Joining me now to talk more about it is John C. Bell, senior nature scientist at the Ottawa Hospital Research Institute and a professor of medicine at the University of Ottawa in Ottawa, Canada. Thanks for talking with us. Dr. Bell.

Dr. JOHN C. BELL: My pleasure.

FLATOW: We know about viruses causing cancer like HPV and cervical. Why do scientists think that viruses can be useful in fighting cancer?

BELL: Well, it's a great question. You know, there are a lot of viruses on the planet. People sort of think of the common ones, the flu and so on, but actually there's hundreds of thousands of viruses on the planet. Some are very bad and they cause disease, and some are quite benign, and we use those benign ones to have vectors for treating disease.

FLATOW: And there is past evidence that viruses can stop tumors form growing?

BELL: You know, there's been lots of what we call anecdotal evidence. I mean, any clinician I've ever met can tell you - or any oncologist say a cancer patient he's had, who's had some tumor miraculously disappear after he had a bout of the flu.

And so what we're trying to do is really understand if that is caused by viruses and if we can use viruses to more routinely treat cancers and eliminate them.

FLATOW: And they have, in those studies, injected the viruses right into the tumor. But what is new about what your study is?

BELL: Yeah, that's exactly right. We've actually been working for quite a long time now, probably about five or six years, with a small biotech company in San Francisco called Generex developing these viruses, and we started off by doing exactly what you said, directly injecting tumors.

But we knew what we really want to do is develop a vector that could be used intravenously, allow it to spread throughout the patient and find tumors wherever they're hidden. And this study in Nature we just reported, we've been successful in doing that. We've treated patients by direct IV infusions of billions of virus particles.

The viruses spread throughout the body, and when they land at a tumor site, they're able to productively infect it.

FLATOW: And are they able to kill it?

BELL: We certainly saw in some patients, at the high doses, some tumor regression. But this study was really what I would call a proof of concept study. We're checking to see if this approach was safe, which it turned out to be very safe, and whether or not we could actually deliver virus to various tumor sites within the body.

And also they were only single doses. So we really weren't hoping to get a lot of therapeutic benefit from it, but even in that case, we did see some patients having tumors shrink a bit.

FLATOW: Do you continue to give these patients the viruses, seeing that it works in some of them?

BELL: You know, we would love to do that, but the way the studies are designed in the first place, with - in accordance with regulatory, you know, desires and so on, we had - we're only able to give a single dose to these patients. We won't be able to follow up with them.

So now we're going to start other new studies in which we'll be able to give multiple doses of the virus intravenously and follow those patients to see if we have a therapeutic benefit.

FLATOW: Do you have trouble finding patients for these studies?

BELL: You know, that unfortunately is not a problem. I work at a cancer center, and really, every day you can see the toll this disease is taken, and many people are sent home and told we have no other treatments for them.

And so then these very brave people like to volunteer for clinical trials and experimental therapeutics, and we've had no problem whatsoever filling up our trials.

FLATOW: And what would be a good first-candidate cancer for you, what type of tumor?

BELL: Well, you know, as again I mentioned this company Generex we're working with, we've done a lot of work with them and found that liver cancer seems to be a good target. And we're now initiating trials, larger trials, in liver cancer specifically, to see if this virus can attack and reduce those tumors and prolong patients' lives.

FLATOW: And melanoma perhaps also?

BELL: Melanoma is a great target. You know, you may have seen there's another company out there called BioVex, it was recently acquired by Amgen, which has done some really nice work with their virus and melanoma, and that was a great target.

We have seen in this virus that we tested and used about 10 years ago by another group and they showed it had a good activity in melanoma. So we really think there's lots of opportunities to develop this virus from many indications, but right now we're trying to focus our efforts on liver cancer.

FLATOW: What is it about the tumor itself that the viruses home in on it like those magic bullets that they're always looking for?

BELL: Yeah, that's a really good question, and the answer is - comes from about 25 years or more of research done by scientists around the world in the cancer field. Really what we've been trying to do is find out what's different between cancer cells and normal cells or cancer tissues and normal tissues.

And through a lot of very basic research, we've identified that there are specific defects found in cancer cells. And what happens as a cancer evolves is it throws away genetic information. It eliminates some of its genes that normally control its growth. This allows a tumor to become immortalized.

But at the same time, it's sort of making a deal with the devil, and it's compromising itself somewhat, and what we discovered about 10 years ago is some of the genetic information that tumors get rid of is information which also controls the ability of an individual cell to fight virus infections.

So normal cells retain that genetic information. They retain their normal growth control. And they are able to fight off virus infections. But tumor cells get rid of that information. They become susceptible, and our idea is to try to infuse as much virus as we possibly can and allow it to find these tumors wherever they're hidden and infect them and destroy them.

FLATOW: Was it a common virus that you used, or was it a special virus?

BELL: This is - this virus is actually a great therapeutic candidate mostly because we know it's extremely safe in humans. It's been used probably for over 200 years now to vaccinate young children, to protect them from infection from smallpox disease.

And so we know we it has an incredibly safe safety record. It's been used around the world hundreds of millions of times and is very, very safe. It also has an ability to travel within the blood system. We knew that from the biology that's been discovered by many other groups. And it has a large what we call cloning capacity or ability to carry extra genetic payloads, which allow us to arm it and make it even more potent.

So for a variety of reasons we picked this virus. It's called vaccinia virus. In fact, you may have a scar on your left shoulder, and I suspect you might, where you were vaccinated with this virus yourself very many years ago. And so we know it's very safe in the human population, and all we've done now is engineer it to be very selective for tumor cells, even more attenuated than the vaccine itself, and with included genes to make it more stimulating in the immune system of the patient.

FLATOW: Well, we wish you good luck, and this is always good to hear some promising new information about cancer therapy.

BELL: Well, you know, I think you're absolutely right. This is a huge problem around the world. Cancer's a big problem for all of societies, and this therapy, I think, is going to be really interesting in the future. It's something completely different than chemo or radiation therapy. Side effects are minimal. So I think this is something that people are really looking forward to.

FLATOW: Well, we'll keep our fingers crossed, and you'll come back and tell us about your further studies. How about that?

BELL: Sounds great.

FLATOW: All right. Thank you very much. John C. Bell, senior scientist at the Ottawa Hospital Research Institute and professor of medicine at the University of Ottawa.

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