Oncolytic Adenoviruses for Cancer Treatment

Abstract

The invention relates to an oncolytic adenovirus for the treatment of cancer, containing a human DNA sequence isolating a promoter conferring selective expression on an adenoviral gene. Said adenovirus can also contain a sequence that optimizes the protein translation of an adenoviral gene regulated by a promoter conferring tumor selectivity. The invention is suitable for use in the treatment of cancer.

What is claimed is: 
     
         1 . An oncolytic adenovirus to treat cancer, the adenovirus comprising: an E1a gene, the E1a gene comprising a delta-24 mutation; a tumor selective promoter upstream of the E1a gene that confers tumor selective expression of the E1a gene; and a myotonic dystrophy insulator upstream of the promoter that comprises a sequence encoding a CTCF binding site and insulates the promoter against transcriptional interference. 
     
     
         2 . The oncolytic adenovirus according to  claim 1 , wherein a Kozak sequence precedes the E1A gene to optimize protein translation. 
     
     
         3 . The oncolytic adenovirus according to  claim 1 , wherein the adenovirus further comprises a capsid modified to increase infectivity or to direct the adenovirus to a receptor present on a tumor cell. 
     
     
         4 . The oncolytic adenovirus according to  claim 1 , wherein a Kozak sequence precedes the E1A gene to optimize protein translation; and a capsid modified to increase infectivity or to direct the adenovirus to a receptor present on a tumor cell. 
     
     
         5 . The oncolytic adenovirus according to  claim 1 , wherein the adenovirus further comprises one or more other genes encoding proteins chosen from prodrug activators, tumor suppressors, and immunostimulators. 
     
     
         6 . The oncolytic adenovirus according to  claim 1 , wherein a Kozak sequence precedes the E1A gene to optimize protein translation; and one or more other genes encoding proteins chosen from prodrug activators, tumor suppressors, and immunostimulators. 
     
     
         7 . The oncolytic adenovirus according to  claim 1 , wherein the adenovirus is a human adenovirus serotype from 1 to 50. 
     
     
         8 . The oncolytic adenovirus according to  claim 7 , wherein the adenovirus is a human adenovirus serotype 5. 
     
     
         9 . The oncolytic adenovirus according to  claim 1 , wherein the promoter is the promoter of human gene E2F1. 
     
     
         10 . The oncolytic adenovirus according to  claim 9 , wherein the E2F1 promoter is modified by the insertion of additional binding sites to E2F. 
     
     
         11 . A pharmaceutical composition comprising an effective amount of the oncolytic adenovirus according to  claim 1 , and one or more components chosen from carriers and pharmaceutically acceptable excipients. 
     
     
         12 . The oncolytic adenovirus according to  claim 1 , wherein the sequence in the insulator comprises the nucleotide sequence of SEQ ID NO:8. 
     
     
         13 . The oncolytic adenovirus according to  claim 1 , wherein the sequence of the insulator comprises position 368 to 1096 of the nucleotide sequence of SEQ ID No:1.