Treating Insulin Secreting Cells

Abstract

This invention relates to a recombinant nucleic acid for an RIP-tk (rat insulin promoter-thymidine kinase) construct that selectively targets insulin secreting cells, such as β-cells, PDX-1 positive human pancreatic ductal carcinomas, and other cells containing certain transcription factors. The present invention is useful in the treatment of pancreatic cancers, such as β-cell insulinomas and can also be used to target pancreatic tumors that do not express insulin, such as pancreatic adenocarcinoma.

1 - 118 . (canceled) 
     
     
         119 . A method of killing a pancreatic tumor cell in a subject, the method comprising:
 a) administering to a subject a nucleic acid comprising a vector with an insulin promoter having SEQ ID NO:1 operatively coupled to a cytotoxic gene, wherein the cytotoxic gene is thereby expressed in a pancreatic tumor cell that does not express insulin,   b) administering a prodrug to said subject, wherein the prodrug is converted to a cytotoxic compound by the action of the protein encoded by said cytotoxic gene and thereby killing the pancreatic tumor cell that does not express insulin.   
     
     
         120 . The method of  claim 119 , where the cytotoxic gene is the thymidine kinase gene. 
     
     
         121 . The method of  claim 119 , where the cytotoxic gene is the thymidine kinase gene and the prodrug is acyclovir, ganciclovir, FIAU or 6-methoxypurine arabinoside. 
     
     
         122 . The method of  claim 121 , wherein the administration is systemic. 
     
     
         123 . The method of  claim 121 , wherein the administration is by direct administration at the site of the pancreatic tumor cell. 
     
     
         124 . A method of treating pancreatic tumor cells in a subject, the method comprising:
 a) administering to a subject a nucleic acid comprising a vector with an insulin promoter having SEQ ID NO:1 operatively coupled to a cytotoxic gene, wherein the cytotoxic gene is thereby expressed in a PDX-1 positive pancreatic tumor cell,   b) administering a prodrug to said subject, wherein the prodrug is converted to a cytotoxic compound by the action of the protein encoded by said cytotoxic gene and thereby killing the PDX-1 positive pancreatic tumor cell.   
     
     
         125 . The method of  claim 123 , where the cytotoxic gene is the thymidine kinase gene. 
     
     
         126 . The method of  claim 123 , where the cytotoxic gene is the thymidine kinase gene and the prodrug is acyclovir, ganciclovir, FIAU or 6-methoxypurine arabinoside. 
     
     
         127 . A method of killing a pancreatic tumor cell in a subject, the method comprising:
 a) administering to a subject a nucleic acid comprising a vector with an insulin promoter having SEQ ID NO:1 operatively coupled to a cytotoxic gene, wherein the cytotoxic gene is thereby expressed in a pancreatic tumor cell,   b) administering a prodrug to said subject, wherein the prodrug is converted to a cytotoxic compound by the action of the protein encoded by said cytotoxic gene and thereby killing the pancreatic tumor cell.   
     
     
         128 . The method of  claim 127 , where the cytotoxic gene is the thymidine kinase gene. 
     
     
         129 . The method of  claim 127 , where the cytotoxic gene is the thymidine kinase gene and the prodrug is acyclovir, ganciclovir, FIAU or 6-methoxypurine arabinoside. 
     
     
         130 . The method of  claim 129 , wherein the administration is systemic. 
     
     
         131 . The method of  claim 129 , wherein the administration is by direct administration at the site of the pancreatic tumor cell.