Optimization and individualization of sodium iodide symporter (NIS)-based gene therapy in glioblastoma based on characterization of tumor heterogeneity and tumor micromilieus (C08)

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In the last funding period we have demonstrated the enormous potential of novel polyplexes and mesenchymal stem cells (MSC) for targeting systemic sodium iodide symporter (NIS) gene delivery in advanced tumor models using NIS as reporter and therapy gene. As an essential step towards clinical application, we will now focus on the optimization and individualization of NIS-based gene therapy for glioblastoma multiforme (GBM) in collaboration with B2. Using a series of GBM mouse models and multiparametric imaging available within this SFB (A1, A7, A10, B2, B12, Z2, Z3), characterization of the heterogeneity of molecular and cellular features of the GBM milieu will be achieved in order to refine our polyplex- and MSC-based targeting strategies. We will further explore combination with radiosensitizing agens, as well as with radiation pretreatment to enhance MSC homing (B4).