,25 However, the particular genetics of MVA are associated with a defective replication in mammalian cells, which greatly reduces its capacity for use as an oncolytic agent.26, 27, 28, 29 Thus, the generation of oncolytic VACV combining the capacity to activate the TLR3-IRF3 pathway with an efficient replication in cancer cells represents a major step toward an efficient VACV-based oncolytic therapy. Here, IRF3 is linked to cancer.