CanSel · Highly selective customizable therapy for metastatic tumors

The ERC starting grant CellControl awarded to the Principal Investigator Yaakov Benenson funds research directed toward rational design and construction of gene circuits and networks for programmable control of cell physiology. One of the potential applications of this research is in the development of next-generation anticancer treatments that incorporate recently acquired knowledge on the complexity of cancer-related regulatory pathways, tumor development and differentiation, and the rise of cancer clones resistant to standard therapies. These new treatments are necessarily more complex than small molecule drugs, yet they are within reach of latest tools developed in gene therapy and they hold the promise of much higher efficacy and lower toxicity as well as robustness to the emergence of resistant clones. Thus our approach could be of great potential for treating metastatic and primary malignant tumors.We have already shown an engineered circuit that selectively detects and eliminates specific cancer cells in vitro. Powered by additional developments in the framework of the ERC starting grant, we have designed an even safer and more selective circuit that can serve as a starting point for pre-clinical and eventually clinical testing. In this proposal we describe proof-of-concept experiments that will show feasibility of our approach in a mouse model. Successful demonstration will pave the way to large-scale translational R&D financed by private investors, and eventually to the deployment of these new therapies in the clinic.