DNA methylation, histone acetylation, epigenetic therapy, immunotherapy, translational research
Biocollection of cancer cell lines established from mesothelioma patients (asbestos exposure-related cancer) and patients samples (serum, plasma, pleural effusion). Immunocompetent rodents models of mesothelioma.
Bioluminescence Resonance Energy Transfer (BRET) assay for the screening of histone deacetylases inhibitors (HDACi) in living cells. Analysis of histone marks (IHC, WB). Measurement of methylation level (Dot-Blot, ELISA, immuno-histochemistry), pyrosequencing. Culture in spheroids. in vitro proliferation (MTT), apoptosis and cell cycle. Real-time PCR. Flow cytometry. Recognition of cancer cells by T lymphocyte clones.
Our laboratory works with Nantes hospital to collect samples from mesothelioma patients. We collaborate with European laboratories (implicated in the previous COST action TD 0905) for the identification of new HDACi. We develop, in collaboration with chemists and polymers specialists, vectorization methods for epigenetic drugs.
The objective of our team is to induce an immunogenic cell death of cancer cells. One of the strategies used is to combine hypomethylating agents with HDACi. We have already demonstrated that this combination increases the expression of cancer testis antigens and then immunogenicity of mesothelioma cells in vitro and in vivo. Unfortunately, clinical evaluations of these drugs was disappointing on solid tumors. In order to improve this strategy, we have engaged two different approaches: 1) identification of new HDACi with better pharmacological properties in vitro and in vivo and 2) development of vectorization strategies for epigenetic drugs to increase their anti-tumor activity and to decrease their toxicity in vivo.
Member of the epigenetics network of Cancéropôle Grand Ouest, France.