US2008221058A1PendingUtilityA1

Tumor-Specific Vector for Gene Therapy

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Assignee: KUPPER JAN-HEINERRPriority: Oct 4, 1999Filed: Feb 13, 2008Published: Sep 11, 2008
Est. expiryOct 4, 2019(expired)· nominal 20-yr term from priority
Inventors:Jan-Heinerr KupperRalph MeyerMirella Meyer-FiccaReinhard Kandolf
C12N 2830/008A61K 48/0058C12N 15/86C12N 2740/13043C12N 15/52A61P 35/00C12N 2750/14143C12N 2710/10343A61P 9/10A61P 43/00
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Claims

Abstract

The invention relates to a vector for the gene therapeutic treatment of tumors, especially in connection with radiotherapy. Said vector is provided with a therapeutic gene in the DNA sequence thereof. The gene is controlled by the promoter for the catalytic subunit of the telomerase or by the promoter for cyclin A.

Claims

exact text as granted — not AI-modified
1 . A vector for treating tumors by gene therapy, comprising a DNA sequence comprising a tissue-specific promoter and at least one therapeutic gene under expression control by said promoter, wherein said promoter is selected from the group consisting of the promoter for the catalytic subunit of telomerase and the promoter for cyclin-A. 
     
     
         2 . The vector of  claim 1 , wherein the therapeutic gene codes for a protein selected from the group of proteins consisting of: cytosine deaminase (CD), herpes simplex-virus thymidine kinase (HSV-TK), DNA-binding domain (DBD) of poly(ADP-ribose) polymerase (PARP), cytotoxic protease 2A and 3C. 
     
     
         3 . The vector of  claim 2 , wherein said cytotoxic protease 2A and 3C is from picornaviruses. 
     
     
         4 . The vector of  claim 2 , wherein said cytotoxic protease 2A and 3C is from group B Coxsackie viruses. 
     
     
         5 . The vector of  claim 2 , wherein said cytotoxic protease 2A and 3C is from group B Coxsackie viruses, serotype B3. 
     
     
         6 . The vector of  claim 2 , wherein the therapeutic gene is a fusion gene coding for a fusion protein of at least two proteins selected from the group of proteins. 
     
     
         7 . The vector of  claim 6 , wherein the therapeutic gene between the sequence regions for the two proteins codes for a peptide linker. 
     
     
         8 . The vector of  claim 7 , wherein the linker comprises glycine. 
     
     
         9 . The vector of  claim 8 , wherein the linker comprises between 8-10 glycines. 
     
     
         10 . The vector of  claim 7 , wherein the fusion gene is selected from the group consisting of: CD-linker-HSV-TK, CD-linker-DBD, CD-linker-2A, CD-linker-3 C, HSV-TK-linker-DBD, HSV-TK-linker-2A, HSV-TK-linker-3C, DBD-linker-2A and DBD-linker-3C. 
     
     
         11 . The vector of  claim 1 , comprising a virus vector. 
     
     
         12 . The vector of  claim 1 , comprising an adenovirus vector. 
     
     
         13 . The vector of  claim 1 , comprising an adeno-associated virus (AAV) vector. 
     
     
         14 . The vector of  claim 1 , wherein between the promoter and the therapeutic gene a positive-feedback system is provided, wherein said system is driven by the promoter and controls by itself the expression of the therapeutic gene. 
     
     
         15 . The vector of  claim 2 , wherein between the promoter and the therapeutic gene a positive-feedback system is provided, wherein said system is driven by the promoter and controls by itself the expression of the therapeutic gene. 
     
     
         16 . The vector of  claim 10 , wherein between the promoter and the therapeutic gene a positive-feedback system is provided, wherein said system is driven by the promoter and controls by itself the expression of the therapeutic gene. 
     
     
         17 . The vector of  claim 14 , wherein the positive-feedback system comprises a T7 promoter and a gene for T7 RNA polymerase. 
     
     
         18 . The vector of  claim 15 , wherein the positive-feedback system comprises a T7 promoter and a gene for T7 RNA polymerase. 
     
     
         19 . The vector of  claim 16 , wherein the positive-feedback system comprises a T7 promoter and a gene for T7 RNA polymerase. 
     
     
         20 . The vector of  claim 17 , wherein the promoter controls the gene for T7 RNA polymerase and the T7 promoter controls the therapeutic gene, said vector further comprising another expression unit comprising the T7 RNA polymerase under the control of the T7 promoter. 
     
     
         21 . The vector of  claim 18 , wherein the promoter controls the gene for T7 RNA polymerase and the T7 promoter controls the therapeutic gene, said vector further comprising another expression unit comprising the T7 RNA polymerase under the control of the T7 promoter. 
     
     
         22 . The vector of  claim 19 , wherein the promoter controls the gene for T7 RNA polymerase and the T7 promoter controls the therapeutic gene, said vector further comprising another expression unit comprising the T7 RNA polymerase under the control of the T7 promoter. 
     
     
         23 . A retrovirus, coding for a vector of  claim 1 . 
     
     
         24 . A method for treating tumors by gene therapy, comprising the step of administering to an individual in need of such therapy a vector of  claim 1 . 
     
     
         25 . The method of  claim 24  for treating neoplastic disorders. 
     
     
         26 . The method of  claim 24 , further comprising the step of treating the individual with radiotherapy. 
     
     
         27 . The method of  claim 24 , further comprising the step of treating the individual with a therapy with cytostatics. 
     
     
         28 . A method for treating benign tumors, comprising the step of administering to an individual in need of such treatment a vector comprising a gene under control of the cyclin-A promoter. 
     
     
         29 . The method of  claim 28  for treating recurring stenoses.

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