Targeted Augmented Cellular therapy against Tumor Initiating Chemoresistant Cells – TACtTICCa

Project leader: Lucia Kučerová
Project duration: 2012 - 2015

Circumventing chemoresistance in tumor cells and achievement of the metastatic spread control still remain major hurdles in the treatment of malignant disease. Human multipotent mesenchymal stromal cells (MSCs) were proven to be efficient delivery vehicles for several enzyme/prodrug combinations to mediate bystander cytotoxicity toward various tumor types. We suggest some evidence-based strategies to augment antitumor effect mediated by genetically modified MSCs in order to achieve eradication of chemoresistant cells which often share the properties of cancer stem cells. We propose to target these clinically relevant cell subpopulations via enzyme purine nucleoside phosphorylase combined with prodrug fludarabine as this might affect both non-dividing qiuescent and chemoresistant tumor cells. We suggest that antitumor treatment with engineered MSCs combined with other modalities might achieve a control over the metastatic spread of chemoresistant tumor cells. Combination treatment which will prevent tumor recurrence should bring an insight into the potential strategies how to eradicate quiescent cells posessing self-renewal capacity. Our therapeutic paradigm will be evaluated on primary human tumor samples and verified on small animal models as a necessary prerequisite for potential future clinical exploitation.

Publications