Means And Methods For Active Cellular Immunotherapy Of Cancer By Using Tumor Cells Killed By High Hydrostatic Pressure and Dendritic Cells

Abstract

Disclosed are pharmaceutical compositions for inducing an immune response against tumor cells comprising tumor cells which are made apoptotic by treatment with high hydrostatic pressure and dendritic cells, and methods for producing such compositions.

1 . A pharmaceutical composition for inducing an immune response against tumor cells comprising
 a) tumor cells which have been rendered apoptotic from treatment with high hydrostatic pressure and   b) dendritic cells.   
     
     
         2 . The pharmaceutical composition according to  claim 1 , characterized in that the tumor cells are treated with hydrostatic pressure for at least 10 minutes at a pressure of at least 200 MPa. 
     
     
         3 . The pharmaceutical composition according to  claim 1 , characterized in that the tumor cells are treated with hydrostatic pressure for 10 minutes to 2 hours at a pressure of 200-250 MPa. 
     
     
         4 . The pharmaceutical composition according to  claim 1 , characterized in that the apoptotic tumor cells are not necrotic. 
     
     
         5 . The pharmaceutical composition according to  claim 1 , characterized in that the tumor cells are derived from tumor cell lines. 
     
     
         6 . The pharmaceutical composition according to  claim 1 , characterized in that the tumor cells are derived from a tumor isolated from the patient to be treated. 
     
     
         7 . The pharmaceutical composition according to  claim 1 , characterized in that the dendritic cells are immature dendritic cells. 
     
     
         8 . The pharmaceutical composition according to  claim 7 , characterized in that the immature dendritic cells are obtained by leukapheresis. 
     
     
         9 . The pharmaceutical composition according to  claim 8 , characterized in that the immature dendritic cells are obtained by leukapheresis and cultivated in vitro in the presence of cytokines. 
     
     
         10 . The pharmaceutical composition according to  claim 1  formulated for use in patients suffering from early or late stage of cancer. 
     
     
         11 . The pharmaceutical composition according to  claim 10 , wherein the composition is formulated for use in patients suffering from a later stage of cancer comprising a prostate cancer with hormone treatment resistant metastatic prostate cancer. 
     
     
         12 . A method of preparing a pharmaceutical composition according to  claim 1 , comprising the steps of:
 a. loading immature dendritic cells with apoptotic tumor cells which have been treated with high hydrostatic pressure, and   b. subsequently maturing the dendritic cells.   
     
     
         13 . A method of treatment of a human patient by cancer vaccination comprising the steps of:
 a. isolating immature dendritic cells tumor cells from the patient,   b. converting said tumor cells to an apoptotic stage by treatment with high hydrostatic pressure,   c. loading the immature dendritic cells with the converted tumor cells of step (b), and   d. maturing the dendritic cells to yield a pharmaceutical composition to be applied to the patient as a cancer vaccine.   
     
     
         14 . A method of treatment of a human patient by cancer vaccination comprising the steps of:
 a. isolating immature dendritic cells from the patient,   b. loading said dendritic cells with tumor cells obtained from a tumor cell line, wherein said tumor cells are converted to an apoptotic stage by treatment with high hydrostatic pressure, and   c. optionally maturing the dendritic cells to yield a pharmaceutical composition to be applied to the patient as a cancer vaccine.