Altered virus

The virus of any one of the preceding claims, wherein the virus further comprises a GM-CSF-encoding gene.

The virus of any one of the preceding claims, wherein the virus further comprises an immune co-stimulatory pathway activating molecule or an immune co-stimulatory pathway activating molecule-encoding gene.

The virus of any one of the preceding claims, further comprising a fusogenic protein-encoding gene.

The virus of any one of the preceding claims, which encodes more than one immune co-stimulatory pathway activating molecule.

The virus of any one of the preceding claims, which is derived from a clinical isolate of a virus.

The virus of any one of the preceding claims, which is a modified clinical isolate of a virus, wherein the clinical isolate kills two or more tumor cell lines more rapidly and/or at a lower dose in vitro than one or more reference clinical isolates of the same species of virus.

The virus of any one of the preceding claims, which is selected from the group consisting of herpes viruses, pox viruses, adenoviruses, retroviruses, rhabdoviruses, paramyxoviruses and reoviruses.

The virus of any one of the preceding claims, which is a herpes simplex virus (HSV).

The virus of any one of the preceding claims, wherein the sequence encoding the CTLA-4 inhibitor, the sequence encoding GM-CSF, the sequence encoding an immune co-stimulatory pathway activating molecule and/or the sequence encoding the fusogenic protein is codon optimized so as to increase expression levels in target cells.

A virus according to any one of the preceding claims, which expresses three heterologous genes, wherein each of the three heterologous genes is driven by a different promoter selected from the CMV promoter, the RSV promoter, the SV40 promoter (SEQ ID) and a retroviral LTR promoter.

A virus according to any one of the preceding claims, which expresses three heterologous genes, wherein each of the three heterologous genes is terminated by a different poly adenylation sequence selected from the BGH, SV40, HGH and RBG poly adenylation sequences.