The present invention relates to the field of disease therapy. More specifically, it relates to a retargeted herpesvirus having a heterologous polypeptide fused to glycoprotein H, wherein the polypeptide targets diseased cells. It also relates to a nucleic acid comprising the genome of the herpesvirus of the invention, a vector comprising this nucleic acid and a cell comprising the nucleic acid or the vector. It further relates to killing cells using the herpesvirus of the invention and to methods for growing it in vitro.

Disclosed are oncolytic viruses comprising chimeric human/mouse CD40 ligands. The chimeric human/mouse CD40 ligand may be MEM40. The oncolytic virus may be replication competent. The oncolytic virus may be an oncolytic herpes simplex virus. Also disclosed are methods comprising administering an oncolytic virus armed with at least one chimeric human/mouse CD40 ligand, for example MEM40, to a patient suffering from cancer.

The present invention relates to the field of disease therapy. More specifically, it relates to a retargeted herpesvirus having a heterologous polypeptide fused to glycoprotein H, wherein the polypeptide targets diseased cells. It also relates to a nucleic acid comprising the genome of the herpesvirus of the invention, a vector comprising this nucleic acid and a cell comprising the nucleic acid or the vector. It further relates to killing cells using the herpesvirus of the invention and to methods for growing it in vitro.

Disclosed are means of treatment of cancer by enhancing efficacy of oncolytic virus ability to eradicate tumors through the destruction/inactivation of cancer endothelial cells through immunological means. In one embodiment of the invention, administration of placental endothelial cells generated antitumor endothelial immune responses are used to sensitize tumors to oncolytic viral entry. In another embodiment, oncolytic viruses are utilized to enhance generation of cancer endothelial specific responses by causing localized inflammation in the tumor endothelium, which enhances efficacy of the tumor endothelial targeting vaccine. In another embodiment, the invention teaches the use of replication deficient oncolytic viruses to deliver proteins to tumor cells in an immunogenic manner such that proteins encoded by the oncolytic viruses induce immunity to tumor endothelial cell antigens.

Disclosed are oncolytic viruses comprising chimeric human/mouse CD40 ligands. The chimeric human/mouse CD40 ligand may be MEM40. The oncolytic virus may be replication competent. The oncolytic virus may be an oncolytic herpes simplex virus. Also disclosed are methods comprising administering an oncolytic virus armed with at least one chimeric human/mouse CD40 ligand, for example MEM40, to a patient suffering from cancer.

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.