Herpes virus vectors for dendritic cells

Abstract

An attenuated herpes virus capable of efficiently infecting a dendritic cell without preventing antigen processing occurring within the infected cell. The attenuated herpes virus and dendritic cells infected with the virus are useful immunotherapeutic methods of treating disease.

1 . A method of stimulating an immune response in a human or animal subject, which method comprises administering to a subject in need thereof an effective amount of an attenuated herpes virus capable of efficiently infecting a dendritic cell without preventing antigen processing occurring within the infected cell, wherein the virus contains mutations which prevent or minimise the expression of viral immediate early genes in the infected cell.  
     
     
         2 . The method of  claim 1  wherein said herpes virus is a herpes simplex virus 1 or 2.  
     
     
         3 . The method of  claim 1  wherein said immediate early genes are the genes encoding ICP0, ICP4, ICP22, ICP27 or functional equivalents thereof.  
     
     
         4 . The method of  claim 1  wherein said virus lacks both a functional gene encoding IPC27 and a functional gene encoding ICP4 and which has an inactivating mutation in the gene encoding VMW65 abolishing its transcriptional activation activity.  
     
     
         5 . The method of  claim 1  wherein said virus lacks functional genes encoding ICP0, ICP4, ICP22 and ICP27.  
     
     
         6 . The method of  claim 1  wherein said virus further lacks a functional gene encoding ICP47.  
     
     
         7 . The method of  claim 1  wherein said virus further lacks a functional gene encoding ICP34.5 or a functional equivalent thereof.  
     
     
         8 . The method of  claim 1  wherein said virus comprises a heterologous gene.  
     
     
         9 . The method of  claim 1  wherein said heterologous gene is operably linked to a control sequence permitting expression of said heterologous gene in a dendritic cell.  
     
     
         10 . The method of  claim 1  wherein said heterologous gene encodes a polypeptide of therapeutic use.  
     
     
         11 . The method of  claim 1  wherein said heterologous gene encodes a polypeptide, the level of expression of which is increased in or on the surface of tumour cells as compared to non-tumour cells; or a polypeptide which is present in or on the surface of the tumour cells but absent from non-tumour cells; or a polypeptide capable of modifying immune responses.  
     
     
         12 . The method of  claim 1  wherein said heterologous gene encodes a polypeptide of parasitic, viral or bacterial origin.  
     
     
         13 . The method of  claim 1  wherein said heterologous gene encodes a tumor antigen.  
     
     
         14 . The method of  claim 1  wherein said virus comprises more than one heterologous gene.  
     
     
         15 . The method of  claim 1  wherein said subject is in need of treatment of or protection against a pathogenic infection.  
     
     
         16 . The method of  claim 1  wherein said subject is in need of treatment of or protection against cancer.  
     
     
         17 . The method of  claim 1  wherein said virus is administered by infecting ex vivo dendritic cells with said virus and administering said infected dendritic cells to said subject.  
     
     
         18 . The method of  claim 17  which further comprises isolating or preparing said dendritic cells from peripheral blood or bone marrow prior to infection.  
     
     
         19 . An ex vivo dendritic cell infected with an attenuated herpes virus capable of efficiently infecting a dendritic cell without preventing antigen processing occurring within the infected cell, which virus contains mutations which prevent or minimise the expression of viral immediate early genes in the infected cell.  
     
     
         20 . The dendritic cell of  claim 19  which is a human dendritic cell.  
     
     
         21 . The dendritic cell of  claim 19 , wherein said virus is a herpes simplex virus 1 or 2.  
     
     
         22 . A process of producing a cell according to  claim 19  comprising infecting, ex vivo, a dendritic cell with an attenuated herpes virus which virus lacks at least one functional immediate early gene.  
     
     
         23 . A pharmaceutical composition comprising a cell according to  claim 19 , together with a pharmaceutically acceptable carrier or dil