WP3: GBM and the Immune Response: Our new approach will consist of combining stem cell based drug delivery in the brain with inhibition of immunosuppression in GBM mouse models. This will be monitored through the use of an optical imaging platform that will exploit the measurements of multiple luciferases simultaneously. Bioluminescent GBM cell lines will be used to establish orthotopic syngeneic and allogeneic brain tumour models in mice. Neuronal and mesenchymal stem cells used as carriers have proven to be a promising and exciting new therapeutic approach for cancer treatment. Drug loaded nanoparticles can be efficiently taken up by stem cells without affecting cell viability. Taking advantage of their specific migratory potential towards GBM, these loaded stem cells can be injected in animals and then therapeutics can be off-loaded. In addition, a strategy for Tregs inhibition will be tested. Indoleamine 2,3 dioxygenase (IDO) expression in GBM cells was proven to increase the recruitment of regulatory cells: the enzymatic inhibition of IDO and the CTLA-4 blockade will be a rational therapeutic platform to assess in our WP3. Nanoparticles delivering EGFRvIII antibodies (erlotinib), new curcumin analogs, angiogenesis inhibitors (bevacizumab) or CD95 ligand (APG101) and indomethacin will be investigated. Optical imaging will allow us to monitor the pharmacokinetics and migration of stem cells together with tumour progression. The in vivo work will involve measurements of both a temporal and spatial nature. WP3 will be led by Dr Chan with three incoming ESRs/ERs and four outgoing ESRs/ERs. The incoming scientists include Prof. Hoehn and also an ER to assist with the MRI and stem cell-nanoparticle work. An ESR will be brought in from LUMC with immunology experience but will in return be given training on optical imaging by PERC. Moreover, we will have access to MSOT where the technique was recently established by the TUM group for detecting GBM.