Methods for treating cancers and restenosis with P21

Abstract

The p21 gene encodes a cyclin dependent kinase inhibitor which affects cell cycle progression, but the role of this gene product in altering tumor growth has not been established. The present inventors have now discovered that the growth of malignant cells in vivo is inhibited by expression of p21. Expression of p21 resulted in an accumulation of cells in G 0 /G 1 , alteration in morphology, and cell differentiation.

1 . A method of treating a cancer in a patient in need thereof comprising administering in vivo a therapeutically effective amount of a composition comprising: 
 (i) an expression vector containing a gene encoding p21; and    (ii) a pharmaceutical carrier.    
     
     
         2 . The method of  claim 1 , wherein said expression vector is a eukaryotic or viral vector.  
     
     
         3 . The method of  claim 2 , wherein said viral vector is an adenoviral vector.  
     
     
         4 . The method of  claim 1 , wherein said cancer is melanoma.  
     
     
         5 . The method of  claim 1 , wherein said cancer is renal cell carcinoma.  
     
     
         6 . The method of  claim 1 , wherein said expression vector is encapsulated in a liposome.  
     
     
         7 . The method of  claim 1 , wherein said patient is human.  
     
     
         8 . The method of  claim 1 , wherein said composition comprises 10 10  expression vectors per ml.  
     
     
         9 . The method of claim L, wherein said composition further comprises an immunotherapeutic agent, genetic therapeutic, cytokine, prodrug converting enzyme or anticancer agent.  
     
     
         10 . The method of  claim 1 , wherein said composition further comprises a second expression vector comprising a gene encoding an immunotherapeutic agent, genetic therapeutic, cytokine or prodrug converting enzyme.  
     
     
         11 . The method of  claim 1 , wherein said expression vector further comprises a second gene encoding an immunotherapeutic agent, genetic therapeutic, cytokine or prodrug converting enzyme; 
 wherein said second gene is in the same reading frame as said gene encoding p21.    
     
     
         12 . A method of treating restenosis in a patient in need thereof comprising administering in vivo a therapeutically effective amount of a composition comprising: 
 (i) an expression vector containing the gene which encodes p21; and    (ii) a pharmaceutical carrier.    
     
     
         13 . A method of treating a cancer in a patient in need thereof comprising administering in vivo a therapeutically effective amount of a composition comprising: 
 (i) an expression vector comprising a gene encoding p21 fused to a gene encoding a prodrug converting enzyme.    
     
     
         14 . The method of  claim 13 , wherein said prodrug converting enzyme is thymidine kinase, cytosine deaminase or β-glucurodinase.  
     
     
         15 . The method of  claim 14 , wherein said composition further comprises a pharmaceutically acceptable carrier.  
     
     
         16 . The method of  claim 14 , wherein said expression vector is a viral vector.