We and others uncovered that cells can be redirected to target tumors becoming powerful anti-cancer molecules delivering tools increasing the microenvironment bioavailability upon specific recognitions. Starting from this concept, we focused on bothmesenchymal stromal/stem cells (MSC) and lymphocytes, generating two main strategies. On one side to modify MSC inducing expression of death ligands capable togenerate selective cancer death and, on the other, to modify lymphocytes by a novel CAR targeting solid tumors. In the first case, we can deliver Tumor necrosis factor Related Apoptosis Inducing Ligand(TRAIL) variants to different cancer models, in particular pancreatic adenocarcinoma and sarcomas. We armed adipose MSC by viral vectors to target a large variety of tumor lines and primary cancer cells both In-Vitro and In-Vivo. We show that MSC can successfully deliver TRAIL variants to rapidly induce tumor death thanks also to synergizing chemotherapy agents within a novel combinatory strategy of multimodal chemo-gene therapy.

In the second case we generated NKT lymphocytes modified to express a proprietary CAR anti-GD2 successfully targeting neuroblastoma, glioblastoma and other GD2+ neoplasms. Finally, in the attempt to further refine the targeting approach, for the first time we included a CAR on MSC delivering TRAIL variants.

Moving these concepts, developed in an academical lab, towardsa go-to-clinic strategy, we have been challenged by a variety of issues that will be shared with the audience including the foundation of an university start-up (Rigenerand srl) that, with more than 500 sqm of classified environment in a cell factory is ready to produce cell and gene therapy products for solid tumors.