Expanded nk cells

Abstract

The present invention relates to expanded NK cells. The NK cells have been expanded ex vivo, are activated and have a cytotoxic phenotype. The cytotoxicity against malignant cells is markedly increased compared to non-expanded NK cells. The invention also relates to a method of treatment.

1 . Natural killer (NK) cells that are ex vivo expanded and said expanded NK cells are active and have a CD56 + CD3 −  phenotype, said phenotype being cytotoxic against autologous tumor cells. 
   
   
       2 . The NK cells according to  claim 1 , wherein said NK cells have an upregulated expression of at least one activating receptor. 
   
   
       3 . The NK cells according to  claim 2 , wherein said activating receptor is upregulated by at least about 50%. 
   
   
       4 . The NK cells according to  claim 2 , wherein said at least one upregulated activating receptor is a natural cytotoxic receptor (NCR). 
   
   
       5 . The NK cells according to  claim 2 , wherein said at least one activating receptor is selected from the group consisting of 2B4, CD8, CD16, CD 27, CD226, NKG2D, NKp30, NKp44 and NKp46. 
   
   
       6 . The NK cells according to  claim 1 , wherein said NK cells have at least about 100% increased cytotoxicity compared to freshly isolated non-expanded NK cells. 
   
   
       7 . The NK-cells according to  claim 1 , wherein said NK cells have been expanded for at least about 5 days. 
   
   
       8 . The NK-cells according to  claim 1 , wherein said NK cells have been expanded for at least about 10 days. 
   
   
       9 . The NK cells according to  claim 1 , wherein said NK cells are cytotoxic against tumor cells, said tumor cells are cells from haematological tumors. 
   
   
       10 . The NK cells according to  claim 1 , wherein said NK cells are cytotoxic against autologous tumor cells, said tumor cells being selected from the group consisting of cells from multiple myeloma, leukaemia and lymphoma. 
   
   
       11 . The NK cells according to  claim 1 , wherein said NK cells are cytotoxic against autologous tumor cells, said tumor cells being cells from multiple myeloma. 
   
   
       12 . The NK cells according to  claim 1 , wherein said NK cells is cytotoxic against autologous tumor cells, said tumor cells being cells from solid tumors. 
   
   
       13 . The NK cells according to  claim 1 , wherein said NK cells are cytotoxic against autologous tumor cells, said tumor cells being selected from the group consisting of cells from hepatocellular tumors, gastrointestinal tumors, ovarian tumors, renal tumors, lung tumors and pancreatic tumors. 
   
   
       14 . The NK cells according to  claim 1 , wherein said NK cells exhibit higher degranulation activity compared to non-expanded and activated NK cells as determined by CD107a expression. 
   
   
       15 . A composition comprising NK cells according to  claim 1 . 
   
   
       16 . Method of curative or prophylactic treatment, wherein NK cells according to  claim 1  are administered to a patient with a malignant disease following allogeneic stem cell transplantation, or a patient undergoing autologous stem cell transplantation for cancer, or a patient with haematological malignancies, or a patient with solid tumors, in a pharmaceutically effective dose. 
   
   
       17 . The method according to  claim 16 , wherein the NK cells are administered to a patient to prevent recurrence of a malignant disease. 
   
   
       18 . The method according to  claim 16 , wherein the NK cells are ex vivo expanded for at least about 5 days prior to administration to the patient. 
   
   
       19 . The method according to  claim 16 , wherein the NK cells are expanded at least about 100 fold prior to administration to the patient. 
   
   
       20 . Method of curative or prophylactic treatment, wherein the composition according to  claim 15  is administered to a patient with a malignant disease following allogeneic stem cell transplantation, or a patient undergoing autologous stem cell transplantation for cancer, or a patient with haematological malignancies, or a patient with solid tumors, in a pharmaceutically effective dose. 
   
   
       21 . The method according to  claim 20 , wherein the composition is administered to a patient to prevent recurrence of a malignant disease. 
   
   
       22 . The method according to  claim 20 , wherein the NK cells are ex vivo expanded for at least about 5 days prior to administration to the patient. 
   
   
       23 . The method according to  claim 20 , wherein the NK cells are expanded at least about 100 fold prior to administration to the patient.