Pooled nk cells from umbilical cord blood associated with antibodies and their uses for the treatment of disease

Abstract

The invention relates to the field of cell therapy, particularly NK cell mediated therapy associated with antibodies. The present invention is directed to methods and compositions for increasing the efficiency of therapeutic natural killer cells (NK cells) and/or antibodies, wherein said methods or compositions comprise the use of pooled NK cells from umbilical cord blood units (UCBs), preferably alloreactive NK cells, in combination with a therapeutic antibody in order to enhance the efficiency of the treatment in human subjects, in particularly through an increase in antibody-dependent cell-mediated cytotoxicity (ADCC) mechanism. The present invention relates to said composition as a pharmaceutical composition, preferably for its use for the treatment of a disease in a human subject in need thereof, preferably wherein said disease is a cancer, infectious or immune disease. Finally, the present invention is also directed to a method of treatment of a disease in a human subject in need thereof, comprising the administering to said subject said pooled NK cells from UCBs, preferably alloreactive, in combination with a therapeutic antibody which can be bound to said NK cells.

1 - 25 . (canceled) 
     
     
         26 . A pharmaceutical kit comprising:
 a first composition comprising a population of alloreactive natural killer cells (NK cells), wherein said cells population is obtained by a method comprising the steps of:   (a) providing at least n umbilical cord blood units (UCB units), or fraction thereof containing said NK cells, with n≧2; and   (b) pooling said at least n UCB units, or fraction thereof containing said NK cells, to produce said population of NK cells; and   a second composition comprising a monoclonal antibody, which can be bound by a natural killer cell Fc receptor, and wherein said monoclonal antibody is directed to a cell receptor antigen of cells of a subject.   
     
     
         27 . The pharmaceutical kit according to  claim 26 , wherein said first composition comprises a population of alloreactive natural killer cells (NK cells), obtained from a mixture of at least n umbilical cord blood units (UCB units), or fraction thereof containing said NK cells, with 3≦n≦50 
     
     
         28 . The pharmaceutical kit according to  claim 26 , wherein said first and second composition are administered simultaneously, separately or sequentially. 
     
     
         29 . The pharmaceutical kit according to  claim 26 , wherein said second composition comprises a monoclonal antibody directed against a cell receptor which is overexpressed by tumoral cells. 
     
     
         30 . The pharmaceutical kit according to  claim 26 , wherein said second composition comprises a monoclonal antibody directed against a cell receptor and wherein said monoclonal antibody is a low or non-fucosylated antibody. 
     
     
         31 . The pharmaceutical kit according to  claim 26 , wherein said second composition comprises a monoclonal antibody which is derived from a milk of a transgenic mammal or from the YB2/0 cell line (ATCC, CRL-1662) or subclone thereof. 
     
     
         32 . The pharmaceutical kit according to  claim 26 , wherein said second composition comprises a monoclonal antibody selected the group consisting of anti-CD20, anti-HER2/Neu and anti-EGFR antibodies. 
     
     
         33 . The pharmaceutical kit according to  claim 26 , wherein said second composition comprises a monoclonal antibody selected the group consisting of TG20, Ublituximab, Trastuzumab and Herceptin-like antibodies. 
     
     
         34 . The pharmaceutical kit according to  claim 26 , wherein said second composition comprises antibody is a human, humanized or chimeric antibody or a fragment thereof. 
     
     
         35 . The pharmaceutical kit according to  claim 26 , wherein said second composition comprises a monoclonal antibody selected from the group consisting of:
 Anti-CD20 (Rituximab, Ublituximab, Obinutuzumab, Ocaratuzumab, Ocrelizumab, Odulimomab, Ofatumumab, Tositumomab; Veltuzumab, FBTA05 or Ibritumomab tiuxetan);   Anti-HER2/Neu (Trastuzumab, Ertumaxomab or Pertuzumab);   Anti-EGFR (Cetuximab, Futuximab, Imgatuzumab, Matuzumab, Necitumumab or Nimotuzumab);   Anti-GD2 (Dinutuximab); and   Anti-CD52 (Alemtuzumab).   
     
     
         36 . The pharmaceutical kit according to  claim 26 , wherein said first composition comprises a population of NK cells obtained by a method further comprising the step of:
 (c) depleting the T cells contained in the pool obtained in step (b); or   (d) depleting the T cells contained in each of the n UCB units before the step (b) of pooling.   
     
     
         37 . The pharmaceutical kit according to  claim 26 , wherein in the first composition, said population of NK cells is obtained by a method comprising further a method of expanding said population of NK cells from cells contained in said n UCB units, and wherein said population of NK cells is further an activated population of NK cells, obtained by a method further comprising a step of activating said population of NK cells. 
     
     
         38 . A method for treating cancer comprising the administration to a subject in need of treatment for cancer of a therapeutically effective amount of a first composition and a second composition, wherein
 said first composition comprising a population of alloreactive natural killer cells (NK cells) which are derived from a mixture of at least n umbilical cord blood units (UCB units), or a mixture of fraction thereof containing said NK cells, with 3≦n≦50; and   said second composition comprising a monoclonal antibody or a specific binding fragment thereof directed to a cell receptor antigen of cells of said subject.   
     
     
         39 . A method for treating cancer according to  claim 38 , wherein said first and second composition are administered simultaneously, separately or sequentially. 
     
     
         40 . A method for treating cancer according to  claim 38 , wherein said cancer is selected from cancers overexpressing a cell receptor at the surface of the tumoral cells of the subject in need of the treatment, and wherein the monoclonal antibody of said second composition is directed against said receptor. 
     
     
         41 . A method for treating cancer according to  claim 38 , wherein said second composition comprises a monoclonal antibody which is a low or non-fucosylated antibody. 
     
     
         42 . A method for treating cancer according to  claim 38 , wherein said second composition comprises a monoclonal antibody which is derived from a milk of a transgenic mammal or from the YB2/0 cell line (ATCC, CRL-1662) or subclone thereof. 
     
     
         43 . A method for treating cancer according to  claim 38 , wherein said second composition comprises a monoclonal antibody selected the group consisting of anti-CD20, anti-HER2/Neu and anti-EGFR antibodies. 
     
     
         44 . A method for treating cancer according to  claim 38 , wherein said second composition comprises a monoclonal antibody selected the group consisting of TG20, Ublituximab, Trastuzumab and Herceptin-like antibodies. 
     
     
         45 . A method for treating cancer according to  claim 38 , wherein cancer to be treated are selected from the group of hematologic malignancy tumor cells, solid tumor cells or carcinoma cells, preferably leukemia cells, acute T cell leukemia cells, chronic myeloid lymphoma (CML) cells, acute myelogenous leukemia cells, chronic myelogenous leukemia (CML) cells, multiple myeloma cells, or lung, colon, prostate, glyoblastoma cancer.