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.

1 . Oncolytic adenovirus for treating cancer comprising a sequence derived from the myotonic dystrophy locus insulating a promoter that confers selective expression on an adenoviral gene. 
     
     
         2 . Oncolytic adenovirus according to  claim 1 , wherein the adenovirus comprises a Kozak sequence that optimizes the protein translation from an adenoviral gene regulated by a promoter that confers tumor selectivity. 
     
     
         3 . Oncolytic adenovirus according to  claim 1  further comprising one or more mutations that confer selective replication in tumors in one or more genes chosen from E1a, E1b, and E4. 
     
     
         4 . Oncolytic adenovirus according to  claim 1 , wherein the adenovirus comprises a Kozak sequence that optimizes the protein translation from an adenoviral gene regulated by a promoter that confers tumor selectivity and further comprising one or more mutations that confer selective replication in tumors in one or more genes chosen from E1a, E1b, and E4. 
     
     
         5 . Oncolytic adenovirus according to  claim 1  comprising a capsid modified to increase infectivity or to direct it to a receiver present in a tumor cell. 
     
     
         6 . Oncolytic adenovirus according to  claim 1 , wherein the adenovirus comprises a Kozak sequence that optimizes the protein translation from an adenoviral gene regulated by a promoter that confers tumor selectivity and further comprising a capsid modified to increase infectivity or to direct it to a receiver present in a tumor cell. 
     
     
         7 . Oncolytic Adenovirus according to  claim 1 , comprising one or more other genes commonly used in the field of gene therapy of cancer chosen from prodrug activators, tumor suppressors, and immunostimulators. 
     
     
         8 . Oncolytic Adenovirus according to  claim 1 , wherein the adenovirus comprises a Kozak sequence that optimizes the protein translation from an adenoviral gene regulated by a promoter that confers tumor selectivity and comprising one or more other genes commonly used in the field of gene therapy of cancer chosen from prodrug activators, tumor suppressors, and immunostimulators. 
     
     
         9 . Oncolytic adenovirus according to  claim 1 , wherein the adenovirus is a human adenovirus derived from a serotype from 1 to 50. 
     
     
         10 . Oncolytic adenovirus according to  claim 1 , wherein the adenovirus comprises a Kozak sequence that optimizes the protein translation from an adenoviral gene regulated by a promoter that confers tumor selectivity, and wherein the adenovirus is a human adenovirus derived from a serotype from 1 to 50. 
     
     
         11 . Oncolytic adenovirus according to  claim 9 , wherein the adenovirus is a human adenovirus serotype 5. 
     
     
         12 . Oncolytic adenovirus according to  claim 10 , wherein the adenovirus is a human adenovirus serotype 5. 
     
     
         13 . Oncolytic adenovirus according to  claim 1 , wherein the promoter that confers selective expression on an adenoviral gene is the promoter of human gene E2F1. 
     
     
         14 . Oncolytic adenovirus according to  claim 1 , wherein the adenovirus comprises a Kozak sequence that optimizes the protein translation from an adenoviral gene regulated by a promoter that confers tumor selectivity, and wherein the promoter that confers tumor selectivity is the promoter of human gene E2F1. 
     
     
         15 . Oncolytic adenovirus according to  claim 13 , wherein the promoter that confers selective expression on an adenoviral gene is a promoter E2F1 modified by the insertion of additional binding sites to E2F. 
     
     
         16 . Oncolytic adenovirus according to  claim 14 , wherein the promoter that confers tumor selectivity is a promoter E2F1 modified by the insertion of additional binding sites to E2F. 
     
     
         17 . Pharmaceutical composition comprising an effective amount of an oncolytic adenovirus according to  claim 1 , and one or more components chosen from carriers and pharmaceutically acceptable excipients. 
     
     
         18 . Pharmaceutical composition comprising an effective amount of an oncolytic adenovirus according to  claim 1 , wherein the adenovirus comprises a Kozak sequence that optimizes the protein translation from an adenoviral gene regulated by a promoter that confers tumor selectivity, and one or more components chosen from carriers and pharmaceutically acceptable excipients. 
     
     
         19 . Use of an oncolytic adenovirus according to  claims 1  for preparing a drug for the treatment or prevention of cancer or a premalignant condition thereof. 
     
     
         20 . Use of an oncolytic adenovirus according to  claims 1  for preparing a drug for the treatment or prevention of cancer or a premalignant condition thereof, wherein the adenovirus comprises a Kozak sequence that optimizes the protein translation from an adenoviral gene regulated by a promoter that confers tumor selectivity.