HSV-1 ONCOLYTIC VIRUS THERAPIES THAT SPECIFICALLY KILL ALT DEPENDENT CANCERS
Recombinant herpes simplex virus (HSV)-1 capable of selectively replicating in alternative lengthening of telomeres (ALT)-dependent tumor cells are described. The recombinant HSV-1 are ICP0-deficient, such as by complete deletion of the ICP0 gene, or mutation of the ICP0 gene sufficient to diminish or eliminate E3 ubiquitin ligase activity of ICP0. In some cases, the recombinant HSV-1 further include additional gene deletions or mutations, such as those that render the virus glycoprotein C (gC) deficient, or include a heterologous gene, such as a gene encoding an immunostimulatory molecule. Methods of treating ALT-dependent cancer, and methods of selectively killing ALT-dependent tumor cells are also described.
1 . A method of treating an alternative lengthening of telomeres (ALT)-dependent cancer in a subject, comprising:
selecting a subject having an ALT-dependent cancer; and
administering to the subject a recombinant herpes simplex virus (HSV)-1 that is infected cell protein 0 (ICP0)-deficient, glycoprotein C (gC)-deficient, or both ICP0-deficient and gC-deficient, thereby treating the ALT-dependent cancer in the subject.
2 . A recombinant herpes simplex virus (HSV)-1 comprising:
a complete deletion of the infected cell protein 0 (ICP0) gene; and
a heterologous gene encoding granulocyte-macrophage colony-stimulating factor (GM-CSF).
3 . A recombinant herpes simplex virus (HSV)-1 comprising:
a complete deletion of the infected cell protein 0 (ICP0) gene;
a mutation of the glycoprotein C (gC) gene, such that the recombinant HSV-1 is gC deficient;
a partial deletion in the infected cell protein 47 (ICP47) gene; and
a heterologous gene encoding granulocyte-macrophage colony-stimulating factor (GM-CSF).