To combat the immune suppressive TME and improve the in vivo efficacy associated with VV CTRL, the immunomodulatory cytokine IL-21 was incorporated into the N1L region of the virus under control of the H5 promoter as described previously.25 27 IL-21 expression, virus replication and cytotoxicity after VVL-21 infection was confirmed in murine, hamster and human PaCa cell lines that all supported virus replication and cytotoxicity (online supplemental figure S3A–F). Here, IL21 is linked to infection.