Recombinant adenoviruses encoding the specific iodine transporter (nis)

Abstract

The present invention relates to the field of gene therapy and the treatment of tumors.

1 . A defective recombinant adenovirus, characterized in that it comprises at least one DNA sequence encoding the specific iodine transporter (Na + /I −  Symporter) NIS or a derivative thereof. 
   
   
       2 . The adenovirus as claimed in  claim 1 , characterized in that the DNA sequence is a cDNA sequence. 
   
   
       3 . The adenovirus as claimed in  claim 1 , characterized in that the DNA sequence is a gDNA sequence. 
   
   
       4 . The adenovirus as claimed in one of  claims 1  to  3 , characterized in that the DNA sequence encodes the specific murine iodine transporter (Na + /I −  Symporter) NIS. 
   
   
       5 . The adenovirus as claimed in one of  claims 1  to  3 , characterized in that the DNA sequence encodes the specific human iodine transporter (Na + /I −  Symporter) NIS. 
   
   
       6 . The adenovirus as claimed in one of  claims 1  to  5 , characterized in that the DNA sequence is placed under the control of a transcriptional promoter allowing its expression in tumor cells. 
   
   
       7 . The adenovirus as claimed in  claim 6 , characterized in that the transcriptional promoter is chosen from viral promoters, preferably from the promoters E1A, MLP, CMV and RSV-LTR, MT-1, SV40. 
   
   
       8 . A defective recombinant adenovirus comprising a cDNA sequence encoding the human iodine transporter NIS under the control of the CMV promoter. 
   
   
       9 . A defective recombinant adenovirus comprising a DNA sequence encoding the iodine transporter NIS or a derivative thereof under the control of a promoter allowing predominant expression in tumor cells. 
   
   
       10 . The defective recombinant adenovirus as claimed in  claim 9 , characterized in that the promoter is chosen from the regulatory sequence of the elastase I gene, the insulin gene, the gene for immunoglobulins, the mouse mammary tumor virus, the PSA gene, the alpha-fetoprotein gene, the alpha 1-antitrypsin gene, the β-globin gene, the gene for basic myelin, the gene for the myosin light chain 2 and the gene for the gonadotrophin-releasing hormone. 
   
   
       11 . The adenovirus as claimed in one of  claims 1  to  10 , characterized in that it that it comprises at least a deletion of all or part of the E1 region and a deletion of all or part of the E4 region. 
   
   
       12 . The adenovirus as claimed in  claim 11 , characterized in that it comprises, in addition, a deletion of all or part of the E4 region. 
   
   
       13 . The adenovirus as claimed in one of  claims 1  to  12 , characterized in that it is a human adenovirus type Ad 2 or Ad 5 or a canine adenovirus type CAV-2. 
   
   
       14 . The adenovirus as claimed in one of  claims 1  to  13 , characterized in that it comprises, in addition, at least one gene encoding a polypeptide involved in a peroxidase system such as the gene for glucose oxidase or for thyroperoxidase. 
   
   
       15 . The use of the adenovirus as claimed in one of  claims 1  to  14 , for the preparation of a pharmaceutical composition intended for treating and/or for inhibiting the growth of tumors. 
   
   
       16 . A pharmaceutical composition comprising one or more defective recombinant adenoviruses as claimed in one of  claims 1  to  14 . 
   
   
       17 . The pharmaceutical composition as claimed in  claim 16 , characterized in that it is in injectable form. 
   
   
       18 . The pharmaceutical composition as claimed in  claim 16  or  17 , characterized in that it comprises between 10 4  and 10 14  pfu/ml, and preferably 10 6  to 10 11  pfu/ml defective recombinant adenoviruses.