Australian researchers are using the common cold as a potential weapon to cure cancer. The technique is called oncolytic virotherapy.
Common viruses have become the latest weapon against cancer. There is the case of the eight-year-old African boy diagnosed with Burkitt's lymphoma at a Ugandan health clinic. He was exposed to the measles virus and in the next few weeks his tumour regressed completely and he entered remission. But only relatively recently have scientists clinically examined the interaction between viruses and cancers in the growing area of oncolytic virotherapy.
Associate Professor Darren Shafren of the University of Newcastle has been looking at the phenomenon for last 15 years. “Even though a lot of the cases seemed anecdotal, there was something in it,” he said. “This phenomenon has always been there but with the latest tools and technologies we have, we can match the right virus with the right cancer.” Shafren is the chief scientific officer with a company called Viralytics, which has been conducting trials using a virus to treat cancer patients.
His work is focused on the coxsackie virus, one of the causes of the common cold. “It's a small virus, it's about one-billionth of the size of a table tennis ball,” he said. “If you look at it under an electron microscope, it looks a bit like a Ferrero Rocher chocolate. The beauty with this particular virus is that it attacks cancer cells.”
The virus is attracted to a certain molecule that is found in abnormally high numbers on cancer cells. While a healthy cell might have five or six of these particular molecules, a cancer cell would have 10,000. “So the virus comes past, recognises all these molecules and all of a sudden it just sticks on there,” Shafren said. “Not only does the virus actively seek out cancer cells [but] once it's inside the cell it replicates until it eventually bursts the cell.” Once the cell breaks open, the patient's antibodies move in, alerting the immune system to the presence of cancer cells. “So one virus goes in, 200 come out and they potentially can go and infect other cells,” Shafren explained. “If they get into the bloodstream, they can be carried to other areas of the body and infect other cancer cells at a distant site.”
“If you look at a one-centimetre tumour, there is something in the order of 10 billion cancer cells in there but it's the size of a marble,” Shafren said. “Micrometastases are a collection of maybe a couple of hundred cells. You'll never see them - they're too small. But the virus can detect those cells and do a mopping operation.”
Having made this discovery, Shafren and his team then needed to work out which cancer cells the virus liked to kill most. Preliminary research shows the common cold virus has a taste for melanoma - the third-most common type of cancer in Australia - but Shafren is also looking at how viruses affect cancers of the breast, prostate, pancreas and lung.
“Chemotherapeutic drugs are quite toxic,” he said. “People have problems with their skin, they lose their hair, they vomit, they lose weight, a lot of their normal cells are damaged in the process of treatment.” He added, “What we find with viruses, the amount of normal cells which are killed in the process of killing cancer cells is much less than with chemotherapy. The toxicities are much lower. So clinicians can potentially give combinations of chemotherapy and the virus. What they are finding in the research is that you can reduce the level of chemo and combine it with virus and still get the same activity against the cancer but you get less toxicity because you have reduced the levels of chemo. The patient may be able to better handle multiple cycles of chemotherapy, where sometimes they have one or two cycles and they get quite sick.”
Sixteen terminally ill cancer patients took part in the researcher's first human trials, in which a small dose of the virus was administered. Some were stabilised and, more importantly, showed no serious side effects from the treatment. Phase two trials are now under way on 63 patients in the US. Once the phase two trials are completed, Viralytics will carry out phase three trials on a larger number of patients.
Shafren said, “It's going to be really personalised medicine… The virus's tolerance profile is much better than all chemotherapies and that, to me, is the big plus. The virus will win hands down on quality of life. There is no doubt that viruses target cancer, there is no doubt that viruses can kill tumours; now, it's the balance of giving the right virus to the right patient. That's the secret - it's going to be who gets the delivery right.”
The chief executive of the Cancer Council Australia, Ian Olver, believes the research is encouraging and is keenly watching developments. “It's a clever way of targeting a tumour,” he said. “The virus infects tumours with particular molecules in them. It has been discovered the molecules are in higher concentrations in some tumours than they are in the rest of the cells in the body. That allows you to target the treatment. But, as always, the proof of the pudding is in the eating. Will it kill tumours as they expect it will? The question is, will it kill every last cell in the tumour? That's what you need to get a cure.”
Viralytics is not the only biotechnology company doing research and clinical trials in the growing and potentially lucrative area of virotherapy. A Boston company called BioVex, Inc, which is using a genetically modified version of the herpes virus to treat melanoma and head and neck cancers, was acquired by global pharmaceutical giant Amgen for $US1 billion in February last year. Canadian group Oncolytics Biotech is in phase three trials using the reovirus - usually a mild virus that can affect the gastrointestinal system or respiratory tract - on patients with head and neck cancers. American company Jennerex has engineered a pox virus called JX-594, which is being tested on patients with liver cancer.
Ethical debate about creating genetically modified viruses continues in the scientific community, with Shafren and his team opting for naturally occurring viruses. “There are two schools of thought: you can use genetically mutated viruses or naturally occurring viruses,” he said. “Then you have the ethical problem of releasing genetically altered viruses into the community. We have gone on one side of the pathway to use naturally occurring viruses. We have been trying to bioselect. We're not changing the virus but we're trying to select the best virus.”
The managing director of Viralytics, Bryan Dulhunty, believes the science has major health - not to mention commercial - potential. “I think what we are seeing now is the birth of a new industry,” he said. “We are following a pretty typical cycle. Ten years ago there was very little science in the area but we now understand how viruses affect cancer. Ten years ago there was almost no science literature. Last year there were about 500 articles on it. With the science there has been a growth in clinical trials - good, reliable, provable data and with that comes the commercial money. While this is still a novel field it's about to enter the mainstream.”
Shafren remains unconvinced there will ever be a cure for the disease, which kills almost 40,000 Australians each year. “Cure is the word I won't use any more…I'm not sure that we're ever going to cure cancer,” he said.
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