Mesenchymal Stromal Cells as Therapeutic Vectors for Metastatic Cancer. (360G-Wellcome-091730_Z_10_Z)

I have shown that activation of mesenchymal stromal cells (MSCs) engineered to deliver TNF-related apoptosis-inducing ligand (TRAIL) eliminates lung metastases when delivered systemically. During the following programme of work, I will improve my understanding of the basic mechanisms of MSC homing to tumours, in vivo tumour cell killing and confirm the most effective form of delivery. I will also delineate an imaging strategy for future translational studies in man. This proposal encompasses thr ee aims with the following specific goals. 1) The first aim will determine the efficacy of different forms of TRAIL expressed on syngeneic and allogeneic MSCs, and shed light on the role of the immune system in tumour cell killing in xenograft and endogenous cancer models closely resembling human disease. 2) The second aim will inform on the mechanism of MSC homing to tumours. The goal is to exploit this knowledge to engineer MSCs to home to tumours in an effective and specific manner. 3) The final aim will define the usefulness of magnetic resonance imaging for the detection and quantification of MSC tumour infiltration for future translational studies of this therapy in humans.