Method for selectively transducing pathologic mammalian cells using a tumor suppressor gene

Abstract

A method for transducing a pathologic hyperproliferative mammalian cell is provided by this invention. This method requires contacting the cell with a suitable retroviral vector containing a nucleic acid encoding a gene product having a tumor suppressive function. Also provided by this invention is a method for treating a pathology in a subject caused by the absence of, or the presence of a pathologically mutated tumor suppressor gene.

1 . A method for treating a heterogenous cell preparation of mammalian cells wherein the preparation contains a population of normal cells and of cells having a pathologic hyperproliferative phenotype, comprising, transducing the cells of the heterogenous cell preparation ex vivo in the absence of a selective medium with a replication-incompetent retroviral vector containing a nucleic acid encoding a p53 or retinoblastoma gene product having a tumor suppressive function, whereby cells having the pathologic hyperproliferative phenotype undergo apoptosis or death or express a mature or benign phenotype. 
     
     
         2 . The method of  claim 1 , wherein the gene product is a wild type retinoplastoma gene product. 
     
     
         3 . The method of  claim 2 , wherein the gene product is a wild type p53 gene product. 
     
     
         4 . (canceled) 
     
     
         5 . The method of  claim 1 , wherein the retroviral vector lacks a selectable marker gene. 
     
     
         6 . (canceled) 
     
     
         7 . The method of  claim 1 , wherein the cells having the pathologic hyperproliferative phenotype are prostate cells, psoriatic cells, thyroid cells, breast cells, colon cells, lung cells, sarcoma cells, leukemic cells or lymphoma cells. 
     
     
         8 . The method of  claim 1 , wherein the time period is less than about ten hours. 
     
     
         9 . The method of  claim 8 , wherein the time period is about four hours. 
     
     
         10 . The method of  claim 1 , wherein cells in the preparation having the pathologic hyperproliferative phenotype come to express a mature or benign phenotype. 
     
     
         11 . The method of  claim 1 , wherein cells in the preparation having the pathologic hyerproliferative phenotype undergo apoptosis or die. 
     
     
         12 - 13 . (canceled) 
     
     
         14 . The method of  claim 1 , wherein the nucleic acid is RNA. 
     
     
         15 . The method of  claim 1 , wherein the mammal is a human. 
     
     
         16 . A method for treating a pathology in a subject caused by the absence of a p53 or retinoblastoma tumor suppressor gene or the presence of a pathologically mutated p53 or retinoblastoma tumor suppressor gene wherein the absence or presence causes a cell to pathologically hyperproliferate comprising:
 obtaining a heterogenous cell preparation of mammalian cells from the subject wherein the preparation contains a population of normal cells and of the pathologically hyperproliferating cell,   treating the preparation according to the method of  claim 1 , and   reinfusing the treated preparation into the subject.   
     
     
         17 . (canceled) 
     
     
         18 . The method of  claim 17 , wherein the tumor suppressor gene is wild type p53 gene. 
     
     
         19 - 20 . (canceled) 
     
     
         21 . The method of  claim 16 , wherein the cells having a pathologic hyperproliferative phenotype are prostate cells, psoriatic cells, thyroid cells, breast cells, colon cells, lung cells, sarcoma cells, leukemic cells or lymphoma cells. 
     
     
         22 . The method of  claim 21 , whereby cells in the preparation having the pathologic hyperproliferative phenotype undergo apoptosis or die. 
     
     
         23 . (canceled) 
     
     
         24 . The method of  claim 16 , wherein the nucleic acid is RNA. 
     
     
         25 . The method of  claim 16 , wherein the retroviral vector lacks a selectable marker gene. 
     
     
         26 . The method of  claim 1 , wherein the cells having the pathologic hyperproliferative phenotype are leukemic cells or lymphoma cells. 
     
     
         27 . The method of  claim 1 , wherein the pathologic hyperproliferative phenotype is a lack of contact growth inhibition.