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.

Provided herein are Vero cell lines that stably express Herpes Simplex Virus (HSV) ICP0 protein. These cells have the same morphology of Vero cells, exhibit stable expression of HSV ICP0 protein, and also efficiently complement replication of HSV ICP0 deficient virus for greater than 20, 30, or even 40 cell passages.

The present invention relates to compositions and methods for treating cancer. More specifically, the present invention relates to compositions of engineered oncolytic viruses for administration to a subject with cancer that specifically lyse tumor cells and actively target tumor cells and cell debris to antigen presenting cells, in order to generate anti-tumor immunity.

The present invention relates to an oncolytic virus comprising: (i) a fusogenic protein-encoding gene and (ii) an immune stimulatory molecule-encoding gene.

In one embodiment, the invention provides an HSV vector comprising a mutant gB and/or a mutant gH glycoprotein, where the viral envelope further comprises a non-native ligand specific for a protein present on the surface of a predetermined cell type. In another embodiment, the invention provides an HSV vector comprising (a) a mutant gC and/or gD envelope glycoprotein which comprises a non-native ligand specific for a protein present on the surface of a predetermined cell type; and (b) a mutant envelope glycoprotein other than gD.

Provided are a recombinant herpes simplex virus, a preparation method and use thereof. The recombinant herpes simplex virus comprises a vector and foreign genes encoding at least two cytokines, wherein the vector is a herpes simplex virus with genes encoding ICP34.5 and ICP47 deleted, and optionally with at least one of genes encoding ICP6, TK and UNG deleted, and the insertion site/sites of the foreign genes is in at least one of the positions where the genes encoding ICP34.5, ICP47, ICP6, TK and UNG are deleted in the vector.

Provided is a recombinant viral vector that expresses a NKG2D activating ligand, such as a UL-16 binding protein. When introduced into a cancer cell, the vector can cause expression of the NKG2D activating ligand, thereby overcoming repression of NK-mediated (or other effector cell, e.g., macrophage) cytotoxicity and causing effector cell-mediated death of the cancer cell. Expression of the NKG2D activating ligand can be controlled by a miRNA present in greater concentration in noncancerous cells than in cancer cells, which can permit selective expression of the ligand in cancer cells and reduced cytotoxicity toward noncancerous cells. The vector can cause expression of an oncolytic factor. When formulated into a pharmaceutical composition and administered to a patient, the vector can be used to treat cancer. The cancer can be a glioma, such as glioblastoma including one with an isocitrate dehydrogenase (IDH) mutation. The vector can be a herpes simplex virus vector, among others.

Provided herein are compositions and methods for vaccination and research applications. In particular, provided herein are non-neuroinvasive herpesviruses and alpha herpesviruses and uses thereof.

The present invention provides a method of treating cancer, which comprises administering a therapeutically effective amount of an oncolytic virus, an inhibitor of the indoleamine 2,3-dioxygenase (IDO) pathway and a further antagonist of an immune co-inhibitory pathway or an agonist of an immune co-stimulatory pathway to a patient in need thereof.

The present invention relates to an oncolytic virus comprising: (i) a fusogenic protein-encoding gene; and (ii) an immune stimulatory molecule-encoding gene.