Source: www.theage.com.au
Author: Rachel Browne

Can the common cold cure cancer? It’s a tempting idea and one on the cutting edge of a new medical research field called oncolytic virotherapy.  Common viruses have become the latest weapon against cancer with a small Australian biotechnology group one of the leaders in the field.

The idea has been around for some time. The classical Greek physician Hippocrates is often credited with the saying, “Give me the power to create a fever, and I shall cure any disease.”

More than 2500 years later,  scientists, including a team from the University of Newcastle, are proving that the theory has merit. Not only did the classical Greeks make the observation, but there have been some instances of cancer patients entering spontaneous remission after exposure to certain viruses in the past century.

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 over the next few weeks his tumour regressed completely and he entered remission.

An incident documented by the British medical journal <em>The Lancet</em> in 1971 described the example of a Hungarian chicken farmer who  had  advanced colorectal cancer. An outbreak of the avian virus Newcastle disease hit the farm, the man became infected and went into 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 the better part of 15 years.

“Even though a lot of the cases seemed anecdotal, there was something in it,” he says. “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, better known as the common cold.

“It’s a small virus, it’s about one-billionth of the size of a table tennis ball,” he says. “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  found in abnormally high numbers on cancer cells. While a healthy cell might have five or six of these  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 says.  “Not only does the virus actively seek out cancer cells, 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 says. “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.”

Attacking those tiny clusters of cancer cells, known as micro-metastases, before they have progressed is the ultimate goal of the treatment but such studies could take years.

“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  says.  “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.

He shies away from the term “Holy Grail” but he believes virotherapy could give cancer patients better quality of life. “Chemotherapeutic drugs are quite toxic,” he says. “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.

“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 the 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 as a result of the treatment. Phase two  trials are now under way on 63 patients in the US.

The US was chosen for the trials because  it  represents about 50 per cent of the market for cancer therapies. The Food and Drug Administration,  the US equivalent of Australia’s Therapeutic Goods Administration, is regarded as having one of the highest regulatory standards in the world.

Once the phase-two  trials are completed, Viralytics will conduct phase-three  trials on larger numbers of patients. It is a long, slow and expensive process —  such studies can cost up to $10 million —  but Shafren believes the benefits will be worth it.

“It’s going to be really personalised medicine,” he says. “The virus’  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.”

Professor Ian Olver, chief executive of the Cancer Council Australia, believes the research is encouraging and is keenly watching developments. “It’s a clever way of targeting a tumour,” he says.

“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 needto get a cure.”

Viralytics is not the only biotechnology company conducting 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 cancer.

American company Jennerex has engineered a pox virus called JX-594 which it is  testing 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 says.

“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.”

While the idea that a virus can cure a disease has been around for 2500 years or so, modern technology makes it sound like a  brave new world.

Viralytics managing director  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 says. “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 stilla novel field it’s about to enter themainstream.”

The University of Newcastle is the biggest shareholder in the company but if the phase-two  trials are successful it is expected that a large pharmaceutical company will step in to take it to phase-three  status, followed by global marketing and distribution.

Despite devoting much of his professional life to improving cancer treatments and quality of life, Shafren is still not convinced  there will ever be a cure for the disease, which claims the lives of almost 40,000 Australians each year.

“Cure is the word I won’t use any more,” he said. “I’m not sure that we’re ever going to cure cancer.”