Methods of treating tumors using natural killer cell lines

Abstract

This invention relates to a natural killer cell line termed NK-92. The invention provides a vector for transfecting a mammalian cell which includes a nucleic acid sequence encoding a cytokine that promotes the growth of NK-92. Additionally, the invention provides an NK-92 cell, or an NK-92 cell modified by transfection with a vector conferring advantageous properties, which is unable to proliferate and which preserves effective cytotoxic activity. The invention further provides a modified NK-92 cell that is transfected with a vector encoding a cytokine that promotes the growth of NK-92 cells. The cell secretes the cytokine upon being cultured under conditions that promote cytokine secretion, and furthermore secretes the cytokine in vivo upon being introduced into a mammal. In a significant embodiment, the cytokine is interleukin 2. The present invention also provides methods of purging cancer cells from a biological sample, of treating a cancer ex vivo in a mammal, and of treating a cancer in vivo in a mammal employing a natural killer cell, such as NK-92 itself, an NK-92 cell which is unable to proliferate and which preserves effective cytotoxic activity, or natural killer cells transfected with a vector encoding a cytokine.

1 - 29 . (canceled)  
     
     
         30 . A method of treating a tumor, comprising administering NK-92 cells to the tumor.  
     
     
         31 . The method of  claim 30 , wherein the administering comprises injecting.  
     
     
         32 . The method of  claim 30 , wherein administering comprises administering the cells adjacent to or into a tumor.  
     
     
         33 . The method of  claim 30 , further comprising administering a cytokine.  
     
     
         34 . The method of  claim 30 , wherein the cells secrete a cytokine.  
     
     
         35 . The method of  claim 34 , wherein the cells comprise a polynucleotide encoding the cytokine.  
     
     
         36 . The method of  claim 34 , wherein the cytokine is interleukin-2.  
     
     
         37 . The method of  claim 34 , wherein the cells comprise cells from a cell line deposited under American Type Culture Collection Accession Number ATCC CRL-2408 or ATCC CRL-2409.  
     
     
         38 . The method of  claim 30 , wherein the cells expresses a thymidine kinase.  
     
     
         39 . The method of  claim 38 , wherein the cell comprises a polynucleotide encoding a thymidine kinase.  
     
     
         40 . The method of  claim 39 , further comprising administering ganciclovir or acyclovir.  
     
     
         41 . The method of  claim 30 , wherein the cells express an altered β 2  microglobulin that does not bind human T-cell receptors.  
     
     
         42 . The method of claim  12 , wherein the microglobulin is human and does not bind T-cell receptors.  
     
     
         43 . The method of  claim 41 , wherein the cells comprise a polynucleotide encoding the altered microglobulin.  
     
     
         44 . The method of  claim 30 , wherein the cells express a receptor for a cancer or a tumor cell antigen, wherein the antigen is not her-2/neu antigen.  
     
     
         45 . The method of  claim 44 , wherein the cells comprise a polynucleotide encoding the receptor.  
     
     
         46 . A method of treating a tumor, comprising: 
 administering to the tumor NK-92 cells;    contacting the cells with a cytokine; and    contacting the cells with a reagent that inactivates NK-92 cell activity.    
     
     
         47 . The method of  claim 46 , wherein the NK-92 cells express an exogenous molecule that when contacted with the reagent, inactivate NK-92 cell activity.  
     
     
         48 . The method of  claim 46 , wherein the reagent comprises γ radiation, and the administration of the radiation precedes administration of the cells to the tumor.  
     
     
         49 . The method of  claim 46 , wherein the reagent comprises ganciclovir or acyclovir, and the cells express thymidine kinase.  
     
     
         50 . The method of  claim 46 , wherein the cytokine comprises interleukin-2.  
     
     
         51 . The method of  claim 50 , wherein the cytokine is expressed by the NK-92 cells.  
     
     
         52 . A device for the treatment of a solid tumor, comprising a syringe comprising NK-92 cells and a carrier.