Here, we report a novel vaccinia virus (VV), VVLΔTKΔN1LΔA41L (with deletion of thymidine kinase (TK), N1L, and A41L genes) armed with interleukin 27 (IL-27), that can cure established tumors and promote long-term antitumor immunity in murine pancreatic cancer tumor models. Here, IL27 is linked to familial pancreatic carcinoma.