Prof Anthony Purcell, Prof Bruce Robinson
While mesothelioma is caused by asbestos exposure, the mutation burden of the mesothelial cells thought to be directly linked to asbestos exposure is relatively low. Using whole genome sequencing, our project will map these mutations while also exploring other immune system targets, or neoantigens, across a variety of sources.
By determining mesothelioma-specific signatures in the antigens selected for presentation on the surface of mesothelioma cells, we will gain an understanding of potential immune targets that are available for T cell recognition. Existing T cell responses to these antigens may have prognostic value and act as immune biomarkers.
What is the need?
The life expectancy for most mesothelioma patients is only 12 months post-diagnosis. Treatment may improve this prognosis, but many of these are palliative, not curative. There is a massive unmet clinical need, and while the current burden of mesothelioma is peaking in Australia, the use of immunotherapy to treat it is in its infancy. However, clinical trials have shown promise, leading to our hypothesis that vaccine-induced augmentation of immune responses will provide clinical benefit in mesothelioma. Exploring the antigenic landscape of mesothelioma could determine which class of antigen is most immunogenic and has the potential to be tested in future vaccine studies.
I strongly believe that our research is poised to be highly translational and that we will be informing immunotherapy for a variety of cancers. This grant provides an avenue to make a real difference in cancer immunotherapy.
What are you trying to achieve?
We will identify a series of candidate vaccine targets in mesothelioma from a variety of novel and more traditional antigen sources. These studies will form the basis for future clinical trials of a mesothelioma vaccine.
How important is this funding?
This funding will allow us to expand on early collborative work to define for the first time the targetable antigens in mesothelioma
|We will undertake cell line-based studies involving the production of triplicate cell pellets. Once pellets are generated the immunopeptidomics analysis and interrogation of the data can begin.
|Patient tumour tissue and pleural effusions will be collected for genomic analysis. We anticipate analysing 10 patients’ tumours preand post-chemotherapy
|Immunogenicity studies using retrospectively synthesised peptides and patient PBMCs to identify valid vaccine targets.
Award / Duration