Cells designed as traps and their use as medicines

Abstract

The present invention discloses a method for transforming hematopoietic cells, in particular, T lymphocytes. The method involves co-culturing target cells, such as T lymphocytes, with pseudo-viral particles comprising a foreign DNA sequence.

What is claimed is:  
     
         1 . A method of transforming hematopoietic cells which comprise T lymphocytes, said method comprising the steps of: 
 (a) providing viral particles comprising a foreign nucleic acid sequence which comprises: 
 (i) a regulatory nucleic acid sequence which is expressable in T lymphocytes and which can be activated by a signal supplied to said T lymphocytes by an antigen that induces graft versus host disease, and  
 (ii) a nucleic acid sequence that encodes a product which, when contacted in situ with a pharmaceutical substance, reacts with said substance to induce destruction of said T lymphocytes, wherein said nucleic acid sequence is operably linked to said regulatory nucleic acid sequence; and  
   (b) culturing said viral particles, under conditions suitable for cell culturing, with said T lymphocytes, thereby transforming said T lymphocytes with said foreign nucleic acid sequence.    
     
     
         2 . The method of  claim 1 , wherein said regulatory sequence is an interleukin- 2  promoter or an interleukin- 2  receptor promoter.  
     
     
         3 . The method of  claim 1 , wherein said viral particles are amphotropic Moloney virus particles produced by a packaging cell line.  
     
     
         4 . A population of T lymphocytes comprising a foreign nucleic acid sequence, wherein said foreign nucleic acid sequence comprises a regulatory nucleic acid sequence which is expressed by an activation signal supplied to said T lymphocytes by an antigen that induces graft versus host disease, and a nucleic acid sequence that encodes a product which, when contacted in situ with a pharmaceutical substance, reacts with said substance to induce destruction of said T lymphocytes, wherein said nucleic acid sequence is operably linked to said regulatory nucleic acid sequence.  
     
     
         5 . The population of T lymphocytes of  claim 4 , wherein said regulatory nucleic acid sequence is an interleukin- 2  promoter or an interleukin- 2  receptor promoter.  
     
     
         6 . The method of  claim 1 , wherein said product, when reacted with said pharmaceutical substance, induces an interruption of nucleic acid replication in said T lymphocytes.  
     
     
         7 . The method of  claim 6 , wherein said product is thymidine kinase.  
     
     
         8 . A method of transforming hematopoietic cells which comprise T lymphocytes, said method comprising the steps of: 
 (a) providing viral particles comprising a foreign nucleic acid sequence which comprises: 
 (i) a regulatory nucleic acid sequence which is expressable in T lymphocytes and which can be activated by a signal supplied to said T lymphocytes by an antigen that induces graft versus host disease, and  
 (ii) a nucleic acid sequence that encodes thymidine kinase which is operably linked to said regulatory nucleic acid sequence; and  
   (b) culturing said viral particles, under conditions suitable for cell culturing, with said T lymphocytes, thereby transforming said T lymphocytes with said foreign nucleic acid sequence.    
     
     
         9 . The population of T lymphocytes of  claim 4 , wherein said product, when reacted with said pharmaceutical substance, induces an interruption of nucleic acid replication in said T lymphocytes.  
     
     
         10 . The population of T lymphocytes of  claim 9 , wherein said product is thymidine kinase.  
     
     
         11 . A method of transforming hematopoietic cells which comprise T lymphocytes, said method comprising the steps of: 
 (a) providing amphotropic retroviral particles comprising a foreign nucleic acid sequence which comprises: 
 (i) a regulatory nucleic acid sequence which is capable of expression in T lymphocytes and which can be activated by a signal supplied to said T lymphocytes by an antigen that induces graft versus host disease, and  
 (ii) a nucleic acid sequence that encodes a product which, when contacted in situ with a pharmaceutical substance, reacts with said substance to induce destruction of said T lymphocytes, wherein said nucleic acid sequence is operably linked to said regulatory nucleic acid sequence; and  
   (b) culturing said amphotropic retroviral particles, under conditions suitable for cell culturing, with said T lymphocytes, thereby transforming said T lymphocytes with said foreign nucleic acid sequence.