Herpes simplex virus expressing foreign genes and method for treating cancers therewith

Abstract

An anti-cancer pharmaceutical composition includes a herpes simplex virus (HSV) vector into which a nucleic acid sequence encoding for an anti-cancer agent selected from interleukin-12, GM-CSF, and CD has been inserted. A method of treatment of a patient suffering from cancer includes administering to the patient the anti-tumor pharmaceutical composition including a HSV vector having a nucleic acid sequence encoding for an anti-cancer agent selected from interleukin-12, GM-CSF, and CD inserted therein.

1 . A method for treating a subject suffering from cancer, said method comprising the step of: administering to a subject a therapeutically effective amount of a replication competent aneurovirulent herpes simplex virus (HSV) comprising a nucleic acid sequence encoding for an agent selected from the group consisting of interleukin-12 and granulocyte macrophage colony stimulating factor, such that an anti-cancer response is induced in the subject.  
     
     
         2 . A method according to  claim 1 , wherein said administering step comprises intratumorally disposing the HSV into the subject.  
     
     
         3 . A method according to  claim 1 , wherein the HSV vector comprises a deletion of the γ 1 34.5 gene.  
     
     
         4 . A method according to  claim 3 , wherein IL-12 genes are inserted within the γ 1 34.5 gene deletion.  
     
     
         5 . A method according to  claim 4 , wherein the IL-12 genes comprise subunits p35 and p40 separated by an IRES sequence.  
     
     
         6 . A method according to  claim 5 , wherein said IL-12 encoding nucleic acid sequence bicistronically expresses the p35 and p40 subunits to produce self-assembling, heterodimeric IL-12 in the HSV vector.  
     
     
         7 . An anti-tumor pharmaceutical composition comprising a replication competent aneurovirulent herpes simplex virus (HSV) vector comprising a nucleic acid sequence encoding for a compound selected from the group consisting of IL-12, GM-CSF, and CD operatively linked to a promoter, and a pharmaceutically acceptable carrier.  
     
     
         8 . A pharmaceutical composition according to  claim 7 , wherein said HSV vector has been transformed with an expression cassette comprising nucleic acid sequences encoding for the p40 and p35 subunits of IL-12, said subunits being separated from each other by an IRES encoding sequence.  
     
     
         9 . A pharmaceutical composition according to  claim 8 , wherein said HSV vector includes a deletion of the γ 1 34.5 gene.  
     
     
         10 . A pharmaceutical composition according to  claim 7 , wherein the expression of the nucleic acid sequence encoding for IL-12 results in constitutive production of IL-12 in vivo.  
     
     
         11 . A pharmaceutical composition according to  claim 7  which has been formulated for injection.  
     
     
         12 . A pharmaceutical composition according to  claim 7 , wherein the promoter is a promoter selected from the group consisting of: eukaryotic, viral, and doxycline inducible.  
     
     
         13 . A method for treating a subject suffering from cancer, said method comprising the step of: administering to a subject a therapeutically effective amount of a replication competent aneurovirulent herpes simplex virus (HSV) comprising a nucleic acid sequence encoding for an agent selected from the group consisting of granulocyte macrophage colony stimulating factor, and cytosine deaminase such that an anti-cancer response is induced in the subject.  
     
     
         14 . An anti-tumor pharmaceutical composition comprising a replication competent herpes simplex virus (HSV) vector comprising a nucleic acid sequence encoding for a compound selected from the group consisting of GM-CSF and CD operatively linked to a promoter, and a pharmaceutically acceptable carrier.  
     
     
         15 . A pharmaceutical composition according to  claim 9  wherein said HSV vector has both copies of the γ 1 34.5 gene being defective.