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Oncolytic adenoviruses OAdV represent a promising strategy for cancer therapy. Despite their activity in preclinical models, to date the clinical efficacy remains confined to minor responses after intratumor injection.

To overcome these limitations, we developed an alternative approach using the combination of the OAdv ICOVIR15 with a replication incompetent adenoviral vector carrying the suicide gene of inducible Caspase 9 Ad.

We showed that MSCs can replicate and release both vectors, enabling significant transduction of the iC9 gene in tumor cells. The activation of iC9 by the chemical inducer of dimerization CID significantly enhanced the antitumor activity of the ICOVIR15, increasing the tumor control and translating into improved overall survival of tumor-bearing mice. CRAd can selectively replicate in and lyse tumor cells, and they are easy to manipulate genetically to incorporate genes of interest. Despite encouraging activity in preclinical models, to date CRAds have revealed only local, transient, and confined responses after intratumor injection in clinical trials.