Herpes simplex virus complex
There is provided an HSV complex which comprises an avirulent HSV and a targeting agent which allows the HSV particle to infect and lyse a specific targeted cell. The inventors have found a way in which avirulent HSV can be targeted to disease cells, e.g. cancer cells, by incorporating an antibody binding domain into one or more viral glycoproteins.
1. A method of producing an HSV which is capable of targeting a tumor cell which expresses a tumor surface antigen comprising:
(a) modifying the HSV genome by incorporating nucleic acid encoding an antibody binding domain which is expressed as a fusion protein with HSV glycoprotein gC or gD, wherein said antibody binding domain is capable of specifically binding to the tumor surface antigen on the tumor cell; and
(b) expressing the modified HSV in a cell.
2. A method according to claim 1 which further comprises modifying the HSV genome so as to prevent γ34.5 gene from expressing a functional protein.
3. A method according to claim 1 wherein said antibody binding domain is in the form of a Single Chain Variable fragment (ScFv).
4. A method according to claim 1 wherein said antibody binding domain is an antibody.
5. A method according to claim 1 wherein the tumour surface antigen is CEA, Her2, CD20 or CD55.
6. A method according to claim 1 wherein the HSV is a γ34.5 deletion mutant.
7. A method according to claim 1 wherein the HSV is HSV-1.
8. A method according to claim 1 wherein the HSV is HSV-1 strain 17.
9. A method according to claim 1 wherein the HSV is HSV1716.
10. A method according to claim 1 further comprising additionally modifying one or more viral glycoproteins.
11. A method according to claim 10 wherein the additional one or more viral glycoproteins are deleted.
12. A method according to claim 10 wherein the additional one or more viral glycoproteins are modified by incorporation of the targeting agent.
13. A method according to claim 10 wherein the additional one or more viral glycoproteins are gD, gC and/or gB.