Abstract: A herpes virus vector is provided with both transcriptional and translational control. Within various embodiments the herpes virus vector is based upon a modified herpes virus and has both ICP27 and ICP34.5 under control of a CEA promoter and miRNA-124/143, respectively, and deletion of at least one copy of terminal repeat long region is provided to increase safety without sacrificing efficacy. The herpes virus vector can also incorporate a virus-expressed cytokine cassette encoding IL-12, IL-15/IL-15RA under the control of CXCR4 promoter.

Abstract: An HSV vector with ICP27 under control of CXCR4 promoter and ICP34.5 under control of miRNA-124/143, wherein the vector has a deletion of one RL and one RS region of the viral genome. Within optional embodiments the mutation is a deletion containing the second copy of the ICP34.5 gene. These constructs provide increased safety without sacrificing efficacy. The HSV vector also incorporates a virus-expressed cytokine cassette encoding IL-12, IL-15/IL-15RA under the control of CMV promoter.

Abstract: Compositions and methods are provided for treating cancer comprising a composition comprising an oncolytic virus and a targeting moiety on the surface of the virus, wherein the oncolytic virus does not encode or express the targeting moiety within various aspects such compositions and methods can be used to treat a wide variety of cancers (e.g., gastrointestinal cancer, such as esophageal, stomach and colon cancers).

Abstract: Vaccines are provided comprising a recombinant virus which expresses an immunomodulatory protein and a target antigen unrelated to said recombinant virus, and a pharmaceutically acceptable excipient.

Abstract: Recombinant herpes simplex viruses are provided having a modified oncolytic herpes virus genome, wherein the modified herpes virus genome has at least one miRNA target sequence operably linked to a first or to a first and a second copy of an ICP34.5 gene. Also provided are pharmaceutical compositions having such recombinant herpes simplex viruses, as well as methods of using such compositions in the treatment of subjects having cancer.