Treatment Using Herpes Simplex Virus

Abstract

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 method of treating a tumor 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 activatable prodrug, and a therapeutically effective amount of an herpes simplex virus (HSV-1) wherein the HSV-1 genome encodes a polypeptide capable of converting the activatable prodrug to a therapeutically active pharmaceutical, wherein the HSV-1 genome has a mutation in each ICP34.5 locus such that the HSV-1 cannot express a functional ICP34.5 gene product, and wherein the HSV-1 is administered at an extratumoral location. 
     
     
         2 . The method of  claim 1  wherein the method involves simultaneous, separate or sequential administration of the HSV-1 and activatable prodrug. 
     
     
         3 . The method 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-1 genome. 
     
     
         4 . The method of  claim 1  wherein the extratumoral administration is into a circulating fluid of the patient. 
     
     
         5 . The method of  claim 1  wherein the extratumoral administration is into the blood of the human in need of treatment. 
     
     
         6 . The method of  claim 1  wherein said activatable prodrug is administered directly to the tumor. 
     
     
         7 . The method of  claim 1  wherein said HSV-1 and activatable prodrug are administered at the same extratumoral location. 
     
     
         8 . The method of  claim 1  wherein said HSV-1 and activatable prodrug are administered to the same circulating fluid. 
     
     
         9 . The method of  claim 1  wherein said HSV-1 and activatable prodrug are administered at different extratumoral locations. 
     
     
         10 . The method of  claim 1  wherein the HSV-1 is oncolytic. 
     
     
         11 . A kit of parts for use in treating a tumor 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 prodrug and the HSV-1 genome encodes an expressible polypeptide capable of converting the activatable prodrug to a therapeutically active pharmaceutical, and wherein the HSV-1 has a mutation in each ICP34.5 locus such that the HSV-1 cannot express a functional ICP34.5 gene product, 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 extratumoral location in order to treat the tumor. 
     
     
         12 . The kit of  claim 11  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-1 genome. 
     
     
         13 . The kit of  claim 11  wherein the HSV-1 is oncolytic.