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A cure for cancer?

Is a vaccine against cancer – one of the most sought after breakthroughs in medical research – possible?

One of the world’s foremost researchers in immuno-regulation, Professor Christopher Parish, thinks the answer is probably yes.

But it won’t be easy.

In a keynote address at The Australian National University’s John Curtin School of Medical Research, where he is Director, Professor Parish has highlighted a promising line of inquiry that he thinks may lead to a universal cancer immunotherapy.

There have already been successes in developing vaccines for diseases that can lead to cancer, such as for hepatitis B and the Australian discovery of a vaccine for the human papillomavirus.

But Professor Parish said there were still no vaccines for many other cancer-causing infections, such as the hepatitis C virus, helicobacter pylori bacteria, flat worms and liver fluke.

And, he pointed out, pathogens only caused about 25 per cent of cancers, meaning other approaches were needed to tackle the majority of forms of the disease.

Professor Parish said the path taken by some has been to try and develop prophylactic vaccines for cancer to try and prevent the disease developing.

He said one of the most promising lines of research in this area has centred around developing a vaccine targeting mucin 1 (MUC1), which is a protein produced in high quantities by cancer tumours.

Researchers have found that people with antibodies against MUC1 have a reduced chance of developing bowel cancer.

The problem, Professor Parish said, was that to properly test the vaccine would involve a trial of around 15 years – a time span far too long for commercial developers.

Another avenue of inquiry is to develop immunotherapeutic vaccines that switch on the immune response to cancer in patients who have already developed the disease.

An early example of this was the use of American physician Dr William Coley of the mycobacteria Bacillus Calmette-Guérin to treat cancer in the late 1800s. About 10 per cent of patients with stage four cancer deliberately infected with a variant of BCG experienced remission, though the toxic formulation produced serious side effects. Nonetheless, a version of the therapy is still used to treat early stage bladder cancer.

The problem, Professor Parish said, was that BCG was not antigen-specific, and it remained unclear how it worked.

The development of prophylactic vaccines for cancer has centred in recent times on stimulating lymphocytes to produce antibodies to specific cancerous antigens.

Here, the big issue researchers have faced is the ability of tumour cells to rapidly mutate, quickly making specific antibodies redundant.

Current immunotherapies include BCG, anti-CTLA-4 antibodies that encourage T-cells to proliferate, and dendritic cell-based vaccines.

Professor Parish said that although anti-CTLA-4 treatments had achieved a 10 per cent improvement in five-year patient survival rates, they involved serious side effects in the intestines, making patients very ill.

Dendritic cell-based techniques such as Provenge involve a complex and costly process (around $90,000 per treatment) tailoring the vaccine to each individual patient, and have been seen to hold much promise.

But Professor Parish said results to date have been “very disappointing”.

A large trial found that it resulted in just a four to 12-month prolongation of life in patients with stage four prostate cancer, and the five-year survival rate was unchanged.

Another approach has been to use liposomes (which act like a molecular glue) to better target dendritic cells to cancer tumours.

One of these treatments, Lipovaxin, is being tested in a small scale clinical trial at Royal Adelaide Hospital, with early results suggesting it has some efficacy with no side effects.

But Professor Parish was more enthusiastic about another approach which has moved away from the idea of targeting specific antigens.

He said the standard prophylactic approach had hit multiple problems, including the difficulty of identifying the antigen early enough, the ability of tumour cells to rapidly mutate, and problems of auto-immunity.

“As researchers, we have been too obsessed with antigen-specific immune response,” Professor Parish said.

Another approach altogether was to induce an innate immune response in patients that tumour cells cannot evade.

For this, neutrophil extracellular traps (NETs) are critical.

NETs are highly toxic nets thrown out by so-called suicide cells which race to the site of infections, and they very effectively trap and kill all cells caught in them.

The problem in the past has been that they are as toxic for self cells as they are for invaders, and have been linked to serious effects such as septic shock, stroke, and cerebral malaria.

But Professor Parish said “very encouraging” work was underway to harness NETs to target tumour cells.

Because they were not antigen specific, he said, it was very difficult for tumour cells to evade them.

However, those hoping for a miracle cancer cure any time soon are likely to be disappointed.

Promising as such research was, Professor Parish said the development of immunotherapy cancer vaccines was still in its infancy.

AR

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