Universal Killer T-Cell

Abstract

The present invention relates to a modified natural killer (NK) cell and its use in personalised medicine. The modified NK cells of the present invention are non-immunogenic, meaning that they are able to be administered to any recipient subject without being rejected by the host immune system (they are “universal”). In a first embodiment the non-immunogenic NK cells are modified to express CD3 to allow a T-cell Receptor (TcR) to be expressed. In a further embodiment the non-immunogenic NK cells are further modified to express a TcR together with the CD3 co-receptor. Co-expression of CD3 with a specific TcR results in the modified NK cells showing antigen-specific cytotoxicity towards target cells. Universal NK cells can thus be targeted against specific antigens, and may thus be used in personalised medicine, particularly in the field of oncology.

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         15 . A method of treatment, which method comprises administering to a subject in need thereof an effective amount of a natural killer (NK) cell, wherein the NK cell expresses CD3 chains CD3γ, CD36δ, CD3ε and CD3ζ, and is modified by recombinant expression to express a T cell receptor (TCR), wherein the TCR specifically binds to an antigen-major histocompatibility complex (MHC) complex expressed by a target cell in the subject; and
 the CD3 chains and the TCR form a functional CD3-TCR complex located at the surface of the NK cell. 
 
     
     
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         23 . The method of  claim 15 , wherein the NK cell is an NK-92 cell. 
     
     
         24 . The method of  claim 15 , wherein the NK cell is a primary NK cell. 
     
     
         25 . The method of  claim 15 , wherein the TCR has specificity towards an antigen on a cancer cell, and the method is for the treatment of cancer. 
     
     
         26 . The method of  claim 15 , wherein the TCR has specificity towards an antigen on an infected cell, and the method is for the treatment of an infection. 
     
     
         27 . The method of  claim 15 , wherein the TCR is not expressed as a fusion protein with a CD3 chain. 
     
     
         28 . The method of  claim 27 , wherein the TCR is root expressed as part of a fusion protein. 
     
     
         29 . The method of  claim 15 , wherein the NK cell is modified to be non-immunogenic. 
     
     
         30 . The method of  claim 15 , wherein the NK cell is modified to disrupt or prevent expression of β 2  microglobulin. 
     
     
         31 . The method of  claim 15 , wherein the NK cell is human and human leukocyte antigen (HLA) negative. 
     
     
         32 . The method of  claim 15 , wherein the NK cell is irradiated, or its proliferative capacity otherwise reduced. 
     
     
         33 . The method of  claim 15 , wherein the NK cell is comprised within a therapeutic composition, said composition further comprising at least one pharmaceutically-acceptable carrier or excipient. 
     
     
         34 . The method of  claim 15 , wherein the NK cell is allogeneic to the subject. 
     
     
         35 . The method of  claim 15 , wherein the NK cell is autologous to the subject. 
     
     
         36 . The method of  claim 15 , wherein the subject is human.