Treatment using herpes simplex virus
The use of Herpes Simplex Virus (HSV) in the treatment of tumour by extratumoural administration of HSV, and the use of HSV in treatment of tumour by combination therapy with a pharmaceutical wherein the HSV and/or pharmaceutical is administered at an extratumoural location, is disclosed.
1. A kit of parts for use in treating a tumour in a human patient by combination therapy, said kit comprising a first container containing an herpes simplex virus (HSV-1) and a second container comprising a pharmaceutical, wherein the pharmaceutical is an activatable nitroreductase (NTR) prodrug and the HSV-1 genome encodes an expressible nitroreductase polypeptide capable of converting the activatable NTR prodrug to a therapeutically active pharmaceutical, and wherein the HSV-1 comprises a deletion, addition, substitution or insertion in each ICP34.5 gene, the kit further comprising instructions for the therapeutically effective administration of said HSV-1 and/or pharmaceutical to a human patient in need of treatment at an extratumoural location in order to treat the tumour, and wherein the tumor is a type that is capable of being treated with an alkylating agent.
2. The kit of claim 1 wherein the NTR prodrug is CB1954.
3. The kit of claim 1 wherein the nucleotide sequence encoding said polypeptide is located entirely within, or so as to overlap, the ICP34.5 encoding nucleotide sequence of the HSV genome.
4. A method of treating a tumour in a human comprising the steps of administering to an individual human in need of treatment a therapeutically effective amount of a pharmaceutical, wherein the pharmaceutical is an nitroreductase (NTR) activatable prodrug, and a therapeutically effective amount of an herpes simplex virus (HSV-1) wherein the HSV-1 genome encodes an expressible nitroreductase polypeptide capable of converting the NTR activatable prodrug wherein the HSV-1 comprises a deletion, addition, substitution or insertion in each ICP34.5 gene, and wherein the HSV-1 is administered at an extratumoural location, and wherein the tumor is a type that is capable of being treated with an alkylating agent.
5. The method of claim 4 wherein the method involves simultaneous, separate or sequential administration of the HSV and activatable prodrug.
6. The method of claim 4 wherein the NTR prodrug is CB 1954.
7. The method of claim 4 wherein the nucleotide sequence encoding said nitroreductase is located entirely within, or so as to overlap, the ICP34.5 encoding nucleotide sequence of the HSV genome.
8. The method of claim 7 wherein the NTR prodrug is CB1954.
9. The method of claim 4 wherein the extratumoural administration is into a circulating fluid of the patient.
10. The method of claim 4 wherein the extratumoural administration is into the patient's blood.
11. The method of claim 4 wherein said activatable prodrug is administered directly to the tumour.
12. The method of claim 4 wherein said HSV and activatable prodrug are administered at the same extratumoural location.
13. The method of claim 4 wherein said HSV and activatable prodrug are administered to the same circulating fluid.
14. The method of claim 4 wherein said HSV and activatable prodrug are administered at different extratumoural locations.
15. The method of claim 4 wherein the HSV is non-neurovirulent.
16. The method of claim 4 wherein the HSV is oncolytic.
17. The method of claim 4 wherein the HSV has an inactivating mutation in one or each ICP34.5 locus of the HSV genome.
18. The method of claim 4 wherein the HSV has a mutation in each ICP34.5 locus such that the HSV cannot express a functional ICP34.5 gene product.
19. The method of claim 4 wherein the HSV is an ICP34.5 null mutant.
20. The method of claim 4 wherein the HSV is an HSV of strain 17.
21. The method of claim 4 wherein the HSV is a mutant of HSV1716.
22. The method of claim 4 wherein the HSV is HSV 1790 deposited under ECACC accession number 03110501.