Oncolytic herpes simplex virus and therapeutic uses thereof

A variant herpes simplex virus (HSV) having an intact endogenous Us12 encoding gene and an intact endogenous Us11 encoding gene, lacking functional ICP34.5 encoding genes,

• wherein each ICP34.5 encoding gene is replaced by a polynucleotide cassette comprising:
• (a) a Us11 encoding gene operably associated with an immediate early (IE) promoter;
• and
• (b) a gene encoding an inhibitor of antigen presentation on class I major histocompatibility complex (MHC) molecules, wherein said inhibitor is capable of inhibiting antigen presentation on the surface of virally infected tumor cells.

A variant herpes simplex virus (HSV) having an intact endogenous Us12 encoding gene and an intact endogenous Us11 encoding gene, lacking functional ICP34.5 encoding genes, wherein each ICP34.5 encoding gene is replaced with a polynucleotide cassette comprising a nucleic acid sequence set forth in one of SEQ ID NO:

• 21, SEQ ID NO:
• 22, SEQ ID NO:
• 23, SEQ ID NO:
• 24 and SEQ ID NO:
• 25.

A variant herpes simplex virus (HSV) having a genome sequence set forth in SEQ ID NO:

• 26, SEQ ID NO:
• 27, SEQ ID NO:
• 28, SEQ ID NO:
• 29, or SEQ ID NO:
• 30.