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 Fr 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 . A NK-92 cell modified to express a Fc receptor on a surface of the cell. 
     
     
         2 . The cell of  claim 1 , wherein the Fc receptor comprises an activating Fcγ receptor 
     
     
         3 . The cell of  claim 1 , wherein the Fc receptor comprises FcγRIII-A (CD16). 
     
     
         4 . The cell of  claim 1 , wherein the Fc receptor comprises a member of a Fc receptor class, the class selected from the group consisting of FCγRI (CD64), FCγRII (CD32), FCγRIII, FcRn, Fcα and Fcε. 
     
     
         5 . The cell of  claim 1 , wherein the Fc receptor comprises a low binding affinity or high binding affinity form. 
     
     
         6 . The cell of  claim 1 , wherein the modification 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. 
     
     
         7 . The cell of  claim 1 , wherein the polynucleotide encodes a polypeptide of SEQ ID NO: 1 or SEQ ID NO:2. 
     
     
         8 . The cell of  claim 1 , further modified to concurrently express at least one associated accessory signaling polypeptide or cytokine, or fragment thereof. 
     
     
         9 - 59 . (canceled) 
     
     
         60 . The cell of  claim 8 , wherein the cytokine comprises interleukin-2. 
     
     
         61 . 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 a the modified NK-92 expressing an Fc receptor of  claim 1 ; and monitoring the target cell for cytotoxicity, cytolysis, or apoptosis, further comprising using a plurality of unmodified NK-92 cells as a negative control. 
     
     
         62 . A method of assaying the efficacy of an antibody to treat a tumor, infection or other lesion, comprising: administering the antibody to the subject; administering modified NK-92 cells expressing an Fc receptor to the subject; and monitoring the tumor, infection or lesion, wherein the efficacy of the antibody correlates with suppression of the tumor, infection or lesion in the subject. 
     
     
         63 . The method of  claim 62 , wherein a plurality of monoclonal antibodies, polyclonal antibodies or chimeric antibodies is administered to the subject. 
     
     
         64 . The method of  claim 62 , wherein an exogenous cytokine, or fragment thereof, is administered to the subject or the cytokine, or fragment thereof, is expressed by the modified NK-92 cells. 
     
     
         65 . The method of  claim 64 , wherein the cytokine is interleukin-2. 
     
     
         66 . A method of treating a human subject, the subject having a tumor, infection or other lesion, the method comprising: administering to the subject antibodies that specifically bind to the tumor, infection or other lesion; and administering to the subject modified NK-92 cells expressing an Fc receptor, wherein a reduction or suppression of the tumor, infection or other lesion indicates a therapeutic response. 
     
     
         67 . The method of  claim 66 , wherein the modification of the NK-92 cell comprises 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. 
     
     
         68 . The method of  claim 66 , wherein the antibodies comprise monoclonal antibodies, polyclonal antibodies or chimeric antibodies. 
     
     
         69 . The method of  claim 68 , wherein at least one antigen binding domain of the chimeric antibody is adapted to bind to the Fc receptor. 
     
     
         70 . The method of  claim 66 , wherein interleukin-2, or fragment thereof, is administered to the subject, or the interleukin-2, or fragment thereof, is expressed by the modified NK-92 cells.