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

在最近的资助期内，我们已经证明了新型多聚体和间充质干细胞（MSC）在晚期肿瘤模型中使用NIS作为报告基因和治疗基因靶向系统性碘化钠同调体（NIS）基因传递的巨大潜力。作为迈向临床应用的重要一步，我们现在将与B2合作，专注于基于nis的多形性胶质母细胞瘤（GBM）基因治疗的优化和个体化。利用一系列GBM小鼠模型和该SFB内可用的多参数成像（A1, A7, A10, B2, B12, Z2, Z3），将实现GBM环境分子和细胞特征异质性的表征，以完善我们基于复合和msc的靶向策略。我们将进一步探索与放射增敏剂以及放射预处理联合使用以增强MSC归巢（B4）。

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).