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A puzzle, a paradox and ultimately a promise of more effective cancer treatments

21 March 2011

A scientific theory is like a jigsaw puzzle. To help piece it together scientists carry out experiments and the results they generate are evaluated carefully to determine where they fit within the overall picture. Sometimes areas of the puzzle come together easily, other times, such as the recent discovery by Prof Franca Ronchese and colleagues, we can be left wondering if the puzzle will ever be solved!

Prof Ronchese and Dr Ian Hermans both head research programmes at the Malaghan Institute focused on exploiting the power and specificity of the immune system to fight disease. For over a decade they have been working on the theory that a vaccine created from a patient's own immune cells and tumour tissue can be used to treat their cancer. Tumours differ from normal cells but they don't always activate a spontaneous immune response in the same way that a virus would. This is because tumours have numerous escape strategies that they use to avoid detection. The cancer vaccine works by helping the immune system to ‘see' the tumour, whilst also providing it with the appropriate signals required to kick-start it into action.

One such signal is a compound from marine sponges called ?-galactosylceramide (?-GalCer), which has been shown in laboratory studies to stimulate even greater vaccine induced anti-tumour immune responses when used in combination with the dendritic cell vaccine. Last year the Health Research Council of New Zealand awarded funding to Dr Hermans and colleagues to use ?-GalCer in combination with the dendritic cell vaccine in a clinical trial for melanoma.

Malaghan PhD graduate Dr Helen Simkins has just had work published in the international scientific Journal of Leukocyte Biology showing, somewhat unexpectedly, that ?-GalCer also causes the death of a specific population of host dendritic cells. The death of these cells occurs shortly after vaccination and appears to be the consequence of the intense inflammation caused by ?-GalCer. In doing so, Dr Simkins' research has revealed an apparent paradox - ?-GalCer stimulates potent anti-tumour immune responses, whilst also signalling the destruction of the cells required for the responses to happen!

So what does this mean for the cancer vaccine? Prof Ronchese emphasises that these results should definitely not prevent the use of ?-GalCer in T cell based immunotherapies, it is still the most promising and powerful adjuvant we have to date. Intriguingly, the results suggest that protecting dendritic cells from death might make the effects of ?-GalCer even more powerful. What they also show however, is that there are still many pieces missing from this puzzle that need to be addressed if we are to fully understand the extraordinary intricacies of the immune system and how best to tap into them to treat disease.