Cancer antigen specific cytotoxic t cell

Abstract

The present invention relates to a pharmaceutical composition for preventing or treating cancer comprising cancer antigen-specific cytotoxic T cells; the pharmaceutical composition comprises about 7×106 cells/mL or more, and of the about 7×106 cells/mL, about 90% or more are CD8+ T cells.

1 . Pharmaceutical composition for preventing or treating cancer comprising cancer antigen-specific cytotoxic T cells,
 wherein the pharmaceutical composition comprises at least about 7×10 6  cells/mL,   and wherein of this about 7×10 6  cells/mL, at least about 90% is CD8+ T cells, and either at least 80% of these CD8+ T cells are CD45RO-expressing cells, or 20% or less of these CD8+ T cells are CD45RA-expressing cells.   
     
     
         2 . Pharmaceutical composition for preventing or treating cancer according to  claim 1 , wherein the pharmaceutical composition is manufactured by a method comprising:
 (a) a step of selecting a cancer antigen-derived epitope present in the cancer patient's blood;   (b) a step of incubating a peripheral blood mononuclear cell (PBMC) isolated from the blood of a cancer patient with the epitope and at least one cytokine selected from the group consisting of IL-2, IL-7, IL-15 and IL-21;   (c) a step of selecting cells expressing both CD8 and 4-1BB from among the cells cultured in step (b); and   (d) a step of incubating the T cells selected in step (c) with anti-CD3 antibody and IL-2.   
     
     
         3 . Pharmaceutical composition for preventing or treating cancer according to  claim 1 , wherein the cancer antigen is at least one selected from the group made up of hTERT, NY-ESO1, MAGE-A3, WT1 and EBV. 
     
     
         4 . Pharmaceutical composition for preventing or treating cancer according to  claim 2 , wherein at least 2 species of epitopes are used at step (a) or (b). 
     
     
         5 . Pharmaceutical composition for preventing or treating cancer according to  claim 2 , wherein step (c) is performed using a closed-system flow cytometer. 
     
     
         6 . Method of manufacturing a pharmaceutical composition for preventing or treating cancer, comprising:
 (a) a step of selecting a cancer antigen-derived epitope present in the cancer patient's blood;   (b) a step of incubating a peripheral blood mononuclear cell (PBMC) isolated from the blood of a cancer patient with the epitope and at least one cytokine selected from the group consisting of IL-2, IL-7, IL-15 and IL-21;   (c) a step of selecting cells expressing both CD8 and 4-1BB from among the cells cultured in step (b); and   (d) a step of incubating the T cells selected in step (c) with anti-CD3 antibody and IL-2; and   wherein the pharmaceutical composition comprises at least about 7×10 6  cells/mL of cancer antigen-specific cytotoxic T cells,   and wherein of this about 7×10 6  cells/mL, at least about 90% is CD8+ T cells, and either at least 80% of these CD8+ T cells are CD45RO-expressing cells, or 20% or less of these CD8+ T cells are CD45RA-expressing cells.   
     
     
         7 . Method according to  claim 6 , wherein the cancer antigen is at least one selected from the group made up of hTERT, NY-ESO1, MAGE-A3, WT1 and EBV. 
     
     
         8 . Method according to  claim 6 , wherein at least 2 species of epitopes are used at step (a) or (b). 
     
     
         9 . Method according to  claim 6 , wherein step (c) is performed using a closed-system flow cytometer. 
     
     
         10 . Method of manufacturing a pharmaceutical composition for preventing or treating cancer, comprising a step of administering a pharmaceutical composition for preventing or treating cancer that comprises a pharmaceutically effective quantity of cancer antigen-specific cytotoxic T cells;
 wherein the pharmaceutical composition comprises at least about 7×10 6  cells/mL of cancer antigen-specific cytotoxic T cells,   and wherein of this about 7×10 6  cells/mL, at least about 90% is CD8+ T cells, and either at least 80% of these CD8+ T cells are CD45RO-expressing cells, or 20% or less of these CD8+ T cells are CD45RA-expressing cells.   
     
     
         11 . Method according to  claim 10 , wherein the pharmaceutical composition is manufactured by a method comprising:
 (a) a step of selecting a cancer antigen-derived epitope present in the cancer patient's blood;   (b) a step of incubating a peripheral blood mononuclear cell (PBMC) isolated from the blood of a cancer patient with the epitope and at least one cytokine selected from the group consisting of IL-2, IL-7, IL-15 and IL-21;   (c) a step of selecting cells expressing both CD8 and 4-1BB from among the cells cultured in step (b); and   (d) a step of incubating the T cells selected in step (c) with anti-CD3 antibody and IL-2.   
     
     
         12 . Method according to  claim 10 , wherein the cancer antigen is at least one selected from the group made up of hTERT, NY-ESO1, MAGE-A3, WT1 and EBV. 
     
     
         13 . Method according to  claim 11 , wherein at least 2 species of epitopes are used at step (a) or (b). 
     
     
         14 . Method according to  claim 11 , wherein step (c) is performed using a closed-system flow cytometer.