Viruses
Herpes Simplex Viruses are disclosed having single-chain antibodies (scFv) embedded in the viral envelope via fusion with glycoprotein D and with glycoprotein H and L.
1. A herpes simplex virus (HSV) comprising an N-terminally truncated glycoprotein D linked to a targeting agent, wherein the N-terminally truncated glycoprotein D has a truncation of at least up to position 260 of the full-length HSV-1 glycoprotein D, wherein the truncation is no greater than or equal to position 274 of the full-length HSV-1 glycoprotein D.
2. A HSV according to claim 1 , wherein the N-terminally truncated glycoprotein D has an extracellular domain comprising at least 42 amino acids.
3. A HSV according to claim 1 , wherein the N-terminally truncated glycoprotein D has an extracellular domain comprising a portion of amino acids corresponding to amino acids 274-315 of the full-length HSV-1 glycoprotein D.
4. A HSV according to claim 1 , wherein targeting agent and the N-terminally truncated glycoprotein D are a fusion protein.
5. A HSV according to claim 1 , wherein the targeting agent is an antibody binding domain.
6. A HSV according to claim 1 , wherein the targeting agent and N-terminally truncated HSV-1 glycoprotein D are a fusion protein, and wherein the targeting agent is an antibody binding domain.
7. A HSV according to claim 1 , wherein the N-terminally truncated glycoprotein D is an N-terminal truncate of a glycoprotein D having the amino acid sequence of SEQ ID NO: 1.
8. A HSV according to claim 1 , wherein the targeting agent is specific for a target selected from the group consisting of GD3, CD38, CD55, CD20, EGRF, HER2/neu, CEA, squamous cell carcinoma antigens 1 and 2, ovarian carcinoma antigen CA125, Mucin 1, prostate-specific membrane antigen, melanoma-associated tumour antigen p97, 5T4 oncofoetal trophoblast glycoprotein, CA19-9, CA72-4 and CA195.
9. A HSV according to claim 1 , wherein the HSV is a mutant of HSV-1.
10. A HSV according to claim 1 , wherein the HSV is non-neurovirulent.
11. A HSV according to claim 1 , wherein the HSV does not comprise an ICP34.5 gene that encodes a functional ICP34.5 gene product.
12. A HSV according to claim 1 , wherein the HSV is a mutant of HSV1716.