Engineered virus

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 a herpes simplex virus (HSV).

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

A virus 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 driven by a different promoter selected from the CMV promoter, the RSV promoter, the SV40 promoter and a retroviral LTR promoter.

A virus 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.

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.