Melanoma vaccine trial raises eyebrows

Professor Peter Hersey is a well-known expert in the field of melanoma research in the country with the world's highest rates of skin cancer: good old sun-drenched Australia.

Interested in using vaccines for the treatment of melanoma, he has developed a vaccine based on the melanoma cell line that was trialed in patients with stages II and III of the disease. Unfortunately, the results from that trial were not found to be statistically significant.

However, a collaboration with Adelaide breast cancer surgeon Brendon Coventry to trial the vaccine in patients with stage IV melanoma, the final and usually fatal stage, has led to some surprising results.

So good are those results - three patients have achieved complete remission, almost unheard of in sufferers of this disease - that the project is now looking for commercial partners to further develop the treatment.

Dr Elaine Stead, commercial development manager with Adelaide Research & Innovation, the commercialisation arm of the University of Adelaide, said while the project is only in its earliest phases, it comes with a few advantages that might interest potential partners. "There are a couple of advantages to the history of this vaccine," Stead says. "Because it has gone through Phase 1 and Phase II t trials in stage II and stage III patients we don't have to start from scratch and the development costs and timeline will be reduced.

"We've done the pilot study and because the safety and toxicity studies have already been undertaken in previous trials, we hope to move straight into a phase II trial.

"What we are looking for is a partner with an interest in oncology or vaccines and some capability in that area to partner us to take this through to phase II trials and confirm that the results we have seen in our pilot study are true and are going to be reflected in a broad, multi-centre clinical trial."

Stead says Hersey has been researching melanoma vaccines for a number of years but was disappointed at the results in his stage II and III patients. However, the collaboration with Coventry has been serendipitous to say the least.

"[Coventry] had a lot of stage IV melanoma patients who he was treating and there really wasn't much he could offer them," she says. "Their cancers had metastasised to their organs and the only treatment option for them was chemotherapy and radiotherapy. All that really does is prolong their lives for a couple of months - generally three to nine months depending on the type of substage."

Coventry asked Hersey if he could try the vaccine in his stage IV patients, who had very little to lose, after all.

"He has administered the vaccine to 20 patients so far and what he has seen is pretty amazing - there have been three cases of complete remission, or 15 per cent of the study group.

"The half-study statistics show that 80 per cent of patients had some response, whether that was a reduction in tumour size of a slowing down of tumour progression or complete regression.

"The mean survival rate was 10 months, which doesn't sound that significant to start with but that was only the half-way point. The three patients who went into complete regression are still with us now and we are five years into the trial."

Stead says the melanoma cell line was derived from a patient and then infected with vaccinia virus, the one used in the smallpox vaccine.

"The virus lyses the melanoma cell line and it's essentially that crude lysate which is used as the vaccine. There are a lot of theories as to why it works but we don't know what the precise mechanism of action is yet but we are planning studies to investigate this next.

"Generally speaking we think that the vaccinia virus antigens elicit the immune response. Combined with the antigens from the melanoma cell line which directs the immune response to target the melanoma cells and effectively eliminate or reduce the number of these cells."

The main advantage of this type of therapy for stage IV patients is the lack of side-effects, she says. "This has no measurable side-effects as far as we can tell. The quality of life of patients is considerably better and that's really important.

"While the responses are extremely positive, the fact that we can treat these patients with very few side effects means their quality of life will be so much more improved than with chemotherapy. That's the other main drawcard."

While the market for the vaccine is not huge, with 150,000 people diagnosed every year, it is a growing problem, especially in Australia. Stead says the market could be worth in excess of $400 million.

And because melanoma is a particularly virulent cancer that has an unfortunate habit of metastasising quickly, it could be the starting point for vaccines for other, more common forms.

Breast cancer, for instance? "We don't know yet but that is certainly something we are thinking about. There are other cancers that seem to respond to immunotherapy so we think this is something that could be translated."