"Prostate cancer is a huge burden of disease in Europe and the world and patients frequently relapse after initial attempts at the cure of localised disease. Cancer vaccination has activity but is only moderately effective. My ERC Advanced Award will use novel translational approaches to take a highly novel vaccine strategy which is excellent in mouse models towards a clinical vaccine for prostate cancer patients.
We have developed a novel strategy for anti-prostate cancer vaccination based on the expression of cDNA libraries in viral vectors. Using vesicular stomatitis virus and prostate and melanoma derived libraries, this is curative in mice and we have established its mechanisms and the key antigenic determinants (Nature Medicine, Nature Biotechnology). We now have to translate this radically new vaccine strategy to the clinic. My ERC Award will be used to develop the vaccine strategy in an adenovirus vector, optimise viral constructs for optimal immunological effect and evaluate these in mouse prostate cancer and human in vitro immune systems. I hypothesised that in the clinic, the emergence of resistant populations of tumour cells from heterogeneous human cancers is likely to be a key factor in clinical failure. We will study resistant and recurrent tumours in mice using immunological and proteomic approaches to tumours and plasma in order to identify potential mechanisms of resistance to the vaccine, and potential blood protein biomarkers of resistance, which will allow us to incorporate strategies to avoid resistance in our clinical programme. In five years we aim to open phase I clinical trials.
The award will fund the essential original translational science to turn the highly novel scientific strategy into a potential clinical strategy. Work to take the optimal adenoviral library vaccine into Good Manufacturing Practice and clinical trial will require commercial partnership and separate funding."
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