Oncolytic virus

Abstract

Malignant tumors that are intrinsically resistant to conventional therapies are significant therapeutic challenges. An embodiment of the present invention provides an oncolytic virus capable of killing target cells, such as a tumor cells. In various embodiments presented herein, the oncolytic virus is armed or encodes a therapeutic polypeptide. In at least one embodiment, a recombinant oncolytic virus has been generated that can specifically replicate in cancer cells leading to their destruction and at the same time secrete robust amounts of a therapeutic polypeptide. Compositions and methods disclosed herein have broad therapeutic applicability.

1 . A recombinant expression vector comprising a nucleic acid comprising a nucleotide sequence encoding an angiostatic polypeptide operably linked to an immediate early HSV promoter IE4/5. 
     
     
         2 . The recombinant expression vector of  claim 1 , wherein:
 the vector is a modified herpes simplex virus.   
     
     
         3 . The recombinant expression vector of  claim 2 , wherein:
 the modified herpes simplex virus is a mutant herpes simplex virus deficient for both copies of its native γ 1 34.5 gene.   
     
     
         4 . The recombinant viral expression vector of  claim 1 , wherein:
 the angiostatic polypeptide comprises a proteolytic polypeptide fragment of BAI1.   
     
     
         5 . The recombinant expression vector of  claim 1 , wherein:
 the nucleic acid encoding the angiostatic polypeptide comprises the nucleotide sequence of SEQ ID NO: 1 or of a degenerate variant of SEQ ID NO: 1.   
     
     
         6 - 16 . (canceled) 
     
     
         17 . A composition, comprising:
 a vector comprising:
 a nucleic acid encoding the polypeptide Chase ABC operably linked to an immediate early HSV IE4/5 promoter. 
   
     
     
         18 . (canceled) 
     
     
         19 . The composition of  claim 17 , wherein said vector is a mutant Herpes Simplex Virus comprising a nucleic acid encoding a replacement γ 1 34.5 gene inserted into an otherwise γ 1 34.5-deleted viral genome, the replacement γ 1 34.5 gene is operably linked to a tumor specific promoter. 
     
     
         20 . The composition of  claim 19 , wherein, the tumor specific promoter comprises a nestin enhancer element. 
     
     
         21 . A recombinant expression vector comprising
 a nucleic acid comprising a nucleotide sequence encoding a Chase ABC polypeptide operably linked to an immediate early HSV promoter IE4/5.   
     
     
         22 . The recombinant expression vector of  claim 21 , wherein:
 the vector is a modified herpes simplex virus.   
     
     
         23 . The recombinant expression vector of  claim 22 , wherein:
 the modified herpes simplex virus is deficient for both copies of its native γ 1 34.5 gene.   
     
     
         24 . The recombinant expression vector of  claim 21 , wherein:
 the nucleic acid sequence encoding a Chase ABC polypeptide comprises the nucleotide sequence of SEQ ID NO: 6 or of a degenerate variant of SEQ ID NO: 6.   
     
     
         25 . The recombinant expression vector of  claim 23 , wherein:
 the nucleic acid sequence encoding a Chase ABC polypeptide comprises the nucleotide sequence of SEQ ID NO: 6 or of a degenerate variant of SEQ ID NO: 6.