Adenovirus comprising an albumin-binding moiety

Abstract

The invention relates to a recombinant adenovirus comprising an albumin-binding moiety on the outer surface of the adenoviral hexon protein, pharmaceutical compositions containing it and its medical use. Particularly, the invention relates to an oncolytic adenovirus comprising a sequence encoding an albumin-binding moiety inserted in the hypervariable region 1 (HVR1) of the hexon protein coding sequence and its use in the prevention and/or treatment of cancer.

1 . A recombinant adenovirus comprising a polynucleotide encoding a hexon protein comprising an albumin-binding moiety inserted within the its hypervariable region 1 (HVR1), wherein the adenovirus is a human adenovirus, and wherein the adenovirus further comprises a polynucleotide encoding a tissue-specific promoter or a tumor-specific promoter. 
     
     
         2 . (canceled) 
     
     
         3 . The recombinant adenovirus according to  claim 1 , wherein the albumin-binding moiety is selected from an albumin-binding domain from streptococcal protein G, an albumin-binding domain from  Peptostreptococcus magnus  protein PAB, an albumin-binding peptide having the core sequence DICLPRWGCLW (SEQ ID NO: 9), and functionally equivalent variants thereof. 
     
     
         4 . The recombinant adenovirus according to  claim 3 , wherein the albumin-binding moiety is the albumin-binding domain 3 from streptococcal protein G. 
     
     
         5 . The recombinant adenovirus according to  claim 1 , wherein the hexon protein contains the albumin-binding moiety inserted after amino acid residue D150 of the hexon protein according to the numbering of the hexon protein of SEQ ID NO: 27. 
     
     
         6 . The recombinant adenovirus according to  claim 1 , wherein the N- and/or the C-terminus of the albumin-binding moiety is connected to the hexon protein by a linker sequence. 
     
     
         7 . The recombinant adenovirus according to  claim 6 , wherein said linker sequence comprises the sequence GSGS (SEQ ID NO: 2). 
     
     
         8 . (canceled) 
     
     
         9 . The recombinant adenovirus according to  claim 1 , wherein the adenovirus is an oncolytic adenovirus. 
     
     
         10 . The recombinant adenovirus according to  claim 1 , wherein said adenovirus further comprises mutations in one or more genes selected from E1a, E1b, E4, and VA-RNAs. 
     
     
         11 . The recombinant adenovirus according to  claim 1 , wherein the adenovirus further comprises one or more capsid modifications to increase adenovirus infectivity and/or to target the adenovirus to a receptor present in a tumour cell. 
     
     
         12 . The recombinant adenovirus according to  claim 11 , wherein the one or modifications comprise insertion of an RGD motif into the H1 loop of the adenoviral fiber protein. 
     
     
         13 . The recombinant adenovirus according to  claim 11  wherein the one or more capsid modifications comprise substitution of a region of the fiber gene with the homologous region from a different adenovirus serotype to form a chimeric adenovirus. 
     
     
         14 . The recombinant adenovirus according to  claim 1 , wherein the adenovirus comprises one or more polynucleotides encoding one or more non-adenoviral genes and said genes are genes used in gene therapy or in vaccination. 
     
     
         15 . The recombinant adenovirus according to  claim 14 , wherein said genes are genes used in cancer gene therapy. 
     
     
         16 . (canceled) 
     
     
         17 . A pharmaceutical composition comprising a therapeutically effective amount of a recombinant adenovirus according to  claim 1  together with a pharmaceutically acceptable carrier. 
     
     
         18 . A method for the treatment of cancer in a mammal comprising administering to said mammal a pharmaceutical composition according to  claim 16 , wherein the oncolytic adenovirus comprises one or more polynucleotides encoding one or more non-adenoviral genes used in cancer gene therapy. 
     
     
         19 . (canceled) 
     
     
         20 . The method according to  claim 18 , wherein the pharmaceutical composition is systemically administered. 
     
     
         21 . The recombinant adenovirus according to  claim 1 , wherein the human adenovirus is selected from human adenovirus serotypes 1 to 57. 
     
     
         22 . The recombinant adenovirus according to  claim 1 , wherein the promoter is selected from a E2F promoter, a telomerase hTERT promoter, a tyrosinase promoter, a prostate-specific antigen promoter, an alpha-fetoprotein promoter, and a COX-2 promoter.