Compositions 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 comprising mature dendritic cells pulsed with tumor cells killed by high hydrostatic pressure, wherein said mature dendritic cells,
 express elevated levels of the co-stimulatory and maturation-associated molecules CD86 and HLA-DR,   induce a higher number of IFN-□-producing T cells,   induce a higher number of tumor antigen-specific T-cells, and/or   are capable of maintaining a lower level of Forkhead Box P3 (FoxP3) positive T regulatory cells,   
       as compared to mature dendritic cells pulsed with tumor cells killed by UV irradiation. 
     
     
         2 . The pharmaceutical composition of  claim 1 , wherein the tumor cells have been killed by rendering them apoptotic by treatment with high hydrostatic pressure of 100 to 300 MPa for 10 min to 12 hours. 
     
     
         3 . The pharmaceutical composition of  claim 1 , where prior to pulsing the dendritic cells were immature. 
     
     
         4 . The pharmaceutical composition of  claim 1 , wherein the pulsed dendritic cells were further matured in vitro by treatment with Poly I:C or LPS. 
     
     
         5 . The pharmaceutical composition of  claim 1 , wherein the dendritic cells were differentiated in vitro from monocytes of the patient to be treated in the presence of IL-4 and GM-CSF. 
     
     
         6 . The pharmaceutical composition of  claim 5 , wherein the monocytes of the patient to be treated were obtained by leukapheresis. 
     
     
         7 . The pharmaceutical composition according to  claim 1 , wherein the tumor cells were apoptotic and not necrotic. 
     
     
         8 . The pharmaceutical composition according to  claim 1 , characterized in that the tumor cells were derived from tumor cell lines. 
     
     
         9 . The pharmaceutical composition according to  claim 1 , characterized in that the tumor cells were derived from a tumor isolated from the patient to be treated. 
     
     
         10 . The pharmaceutical composition according to  claim 1  formulated for use in treating patients suffering from an early stage of cancer. 
     
     
         11 . The pharmaceutical composition according to  claim 10 , wherein the composition is formulated for use in treating patients suffering from an early stage of cancer selected from prostate cancer and ovarian cancer. 
     
     
         12 . The pharmaceutical composition according to  claim 1  formulated for use in treating patients suffering from a late stage of cancer. 
     
     
         13 . The pharmaceutical composition according to  claim 12 , wherein the composition is formulated for use in treating patients suffering from a late stage of cancer selected from prostate cancer and ovarian cancer.