Genetically modified human natural killer cell lines

Abstract

The invention provides a natural killer cell, NK-92, modified to express an Fc receptor on the surface of the cell, such as CD16 (FcγRIII-A), or other Fcγ or Fc receptors. The modified NK-92 cell can be further modified to concurrently express an associated accessory signaling protein, such as FcεRI-γ,TCR-ζ, or to concurrently express interleukin-2 (IL-2) or other cytokines. Additional methods are disclosed for various assays, assessments, and therapeutic treatments with the modified NK-92 cells.

1 - 59 . (canceled) 
     
     
         60 . A composition comprising a pharmaceutically acceptable carrier and modified NK-92 cells, for use as a medicament for treating a subject, the subject having a tumor or infection, wherein the modification of the NK-92 cell comprises a polynucleotide sequence encoding a polypeptide having at least 90% sequence identity with SEQ ID NO:1 or SEQ ID NO:2 and having Fc receptor activity. 
     
     
         61 . The composition of  claim 60 , wherein the modification of the NK-92 cell comprises a polynucleotide comprising a polynucleotide sequence encodes a polypeptide having at least 95% sequence identity with SEQ ID NO:1 or SEQ ID NO:2 and having Fc receptor activity. 
     
     
         62 . The composition of  claim 60 , wherein the composition further comprises monoclonal or polyclonal antibodies. 
     
     
         63 . The composition of  claim 60 , wherein the composition further comprises chimeric antibodies. 
     
     
         64 . The composition of  claim 63 , wherein at least one antigen binding domain of the chimeric antibody is adapted to bind to the Fc receptor. 
     
     
         65 . The composition of  claim 60 , wherein the cells express interleukin-2. 
     
     
         66 . The composition of  claim 60 , wherein a reduction or suppression of the tumor or infection indicates a therapeutic response. 
     
     
         67 . The composition of  claim 60 , wherein the subject is human. 
     
     
         68 . The cell of  claim 60 , wherein the Fc receptor comprises a low binding affinity or high binding affinity form. 
     
     
         69 . The cell of  claim 60 , wherein the modification comprises introducing a polynucleotide sequence encoding a polypeptide having a sequence as set forth in SEQ ID NO: 1 or SEQ ID NO:2. 
     
     
         70 . The cell of claim  1 , further modified to concurrently express interleukin-2 (IL-2). 
     
     
         71 . The cell of  claim 60 , for use in treating a subject having a tumor or infection, wherein the cell is for use in combination with an antibody that specifically binds to the tumor, infection or other lesion. 
     
     
         72 . A method for in-vitro assessment of the efficacy of an antibody to induce cell death, the method comprising:
 exposing a target cell to the antibody;   exposing the target cell to an NK-92 cell modified to express an Fc receptor on a surface of the NK-92 cell; and   monitoring the target cell for cytotoxicity, cytolysis, or apoptosis, wherein the modification of the NK-92 cell comprises introducing a polynucleotide comprising a polynucleotide sequence encoding a polypeptide having at least 90% sequence identity with SEQ ID NO:1 or SEQ ID NO:2, further comprising using a plurality of unmodified NK-92 cells as a negative control.   
     
     
         73 . The method of  claim 72 , wherein the associated accessory signaling polypeptide comprises FccRI-y (SEQ ID NO:5) or TCR- (SEQ ID NO:7). 
     
     
         74 . The method of  claim 72 , further comprising exposing the cells to a cytokine, wherein the cytokine is interleukin-2. 
     
     
         75 . The cell of  claim 68 , for treating a subject having a tumor or infection, wherein the cell is for use in combination with an antibody that specifically binds to the tumor, infection or other lesion. 
     
     
         76 . The cell of  claim 70 , for treating a subject having a tumor or infection, wherein the cell is for use in combination with an antibody that specifically binds to the tumor, infection or other lesion.