Herpes virus strains

Abstract

The present invention provides a herpes virus with improved oncolytic properties which comprises a gene encoding an immunomodulatory cytokine and which lacks a functional ICP34.5 gene and a functional ICP47 encoding gene.

1 - 43 . (canceled) 
     
     
         44 . A herpes simplex virus 1 (HSV1) which:
 (i) lacks a functional ICP34.5 encoding gene;   (ii) lacks a functional ICP47 encoding gene; and   (iii) comprises a gene encoding an immunostimulatory protein, wherein said gene is under the control of a promoter, and wherein said promoter is a ubiquitous promoter or a viral promoter.   
     
     
         45 . The HSV1 of  claim 44 , wherein said promoter is a viral promoter. 
     
     
         46 . The viral promoter of  claim 45 , wherein said viral promoter is a cytomegalovirus (CMV) promoter. 
     
     
         47 . The CMV promoter of  claim 46 , wherein said CMV promoter is a CMV immediate early (IE) promoter. 
     
     
         48 . The HSV1 of  claim 44 , wherein said immunostimulatory protein is a cytokine. 
     
     
         49 . The HSV1 of  claim 45 , wherein said immunostimulatory protein is a cytokine. 
     
     
         50 . The HSV1 of  claim 46 , wherein said immunostimulatory protein is a cytokine. 
     
     
         51 . The HSV1 of  claim 47 , wherein said immunostimulatory protein is a cytokine. 
     
     
         52 . The HSV1 of  claim 48 , wherein said immunostimulatory protein is human GM-CSF. 
     
     
         53 . The HSV1 of  claim 49 , wherein said immunostimulatory protein is human GM-CSF. 
     
     
         54 . The HSV1 of  claim 50 , wherein said immunostimulatory protein is human GM-CSF. 
     
     
         55 . The HSV1 of  claim 51 , wherein said immunostimulatory protein is human GM-CSF. 
     
     
         56 . The HSV1 of  claim 44 , wherein said herpes simplex virus 1:
 (iv) lacks a functional gene encoding ICP6, glycoprotein H or thymidine kinase.   
     
     
         57 . A herpes simplex virus 1 (HSV1) which:
 (i) lacks a functional ICP34.5 encoding gene;   (ii) lacks a functional ICP47 encoding gene; and   (iii) comprises a gene encoding an immunostimulatory protein, wherein said gene encoding an immunostimulatory protein is inserted into the former site of the ICP34.5 encoding gene.   
     
     
         58 . The HSV1 of  claim 57 , wherein said immunostimulatory protein is a cytokine. 
     
     
         59 . The HSV1 of  claim 58 , wherein said immunostimulatory protein is human GM-CSF. 
     
     
         60 . The HSV1 of  claim 57 , wherein said herpes simplex virus 1:
 (iv) lacks a functional gene encoding ICP6, glycoprotein H or thymidine kinase.   
     
     
         61 . A herpes simplex virus 1 (HSV1) which:
 (i) lacks a functional ICP34.5 encoding gene;   (ii) lacks a functional ICP47 encoding gene; and   (iii) comprises a gene encoding human GM-CSF, wherein said gene is under the control of a cytomegalovirus (CMV) immediate early (IE) promoter.   
     
     
         62 . The HSV1 of  claim 44 , wherein said herpes simplex virus 1 is a clinical isolate. 
     
     
         63 . The HSV1 of  claim 57 , wherein said herpes simplex virus 1 is a clinical isolate. 
     
     
         64 . The HSV1 of  claim 61 , wherein said herpes simplex virus 1 is a clinical isolate. 
     
     
         65 . A method of treating cancer in a patient, wherein said method comprises administering to said patient a therapeutically effective amount of a herpes simplex virus 1 (HSV1),
 wherein said HSV1:
 (i) lacks a functional ICP34.5 encoding gene; 
 (ii) lacks a functional ICP47 encoding gene; and 
 (iii) comprises a gene encoding an immunostimulatory protein, wherein said gene is under the control of a promoter, and wherein said promoter is a ubiquitous promoter or a viral promoter. 
   
     
     
         66 . The method according to  claim 65 , wherein said HSV1 is administered to a tumor via intratumoral injection. 
     
     
         67 . The method according to  claim 65 , wherein said cancer is selected from the group consisting of prostate cancer, breast cancer, lung cancer, liver cancer, endometrial cancer, bladder cancer, colon or cervical carcinoma, adenocarcinoma, melanoma, lymphoma, glioma and sarcoma. 
     
     
         68 . The method according to  claim 66 , wherein said cancer is selected from the group consisting of prostate cancer, breast cancer, lung cancer, liver cancer, endometrial cancer, bladder cancer, colon or cervical carcinoma, adenocarcinoma, melanoma, lymphoma, glioma and sarcoma. 
     
     
         69 . The method according to  claim 65 , wherein said cancer is melanoma. 
     
     
         70 . The method according to  claim 66 , wherein said cancer is melanoma.