Use of anti third party central memory t cells for anti-leukemia/lymphoma treatment

Abstract

A method of treating a disease in a subject in need thereof is disclosed. The method comprising: (a) transplanting a non-syngeneic cell or tissue graft to the subject; and (b) administering to the subject a therapeutically effective amount of an isolated population of cells comprising non-graft versus host (GVHD) inducing anti-third party cells having a central memory T-lymphocyte (Tcm) phenotype, the cells being tolerance-inducing cells and capable of homing to the lymph nodes following transplantation, and further wherein the cells are either: (i) non-syngeneic with both the subject and the graft; or (ii) non-syngeneic with the graft and syngeneic with the subject, thereby treating the subject.

What is claimed is: 
     
         1 . A method of generating an isolated population of cells comprising non-graft versus host (GVHD) inducing anti-third party cells having a central memory T-lymphocyte (Tcm) phenotype, said Tcm phenotype comprising a CD8 + /CD62L + /CD45RO+ signature and wherein at least 50% of the isolated population of cells have said signature, said cells being tolerance-inducing cells and capable of homing to the lymph nodes following transplantation, the method comprising:
 (a) contacting peripheral blood mononuclear cells (PBMC) with a third party antigen or antigens in the presence of IL-21 under conditions which allow elimination of graft versus host (GVH) reactive cells; and   (b) culturing said cells resulting from step (a) in the presence of IL-15 in an antigen free environment under conditions which allow proliferation of cells comprising said Tcm phenotype, thereby generating the isolated population of cells.   
     
     
         2 . The method of  claim 1 , wherein said conditions which allow elimination of GVH reactive cells comprise culturing for 1-5 days. 
     
     
         3 . The method of  claim 1 , wherein said culturing in the presence of IL-15 is effected for 3-30 days. 
     
     
         4 . The method of  claim 1 , wherein said conditions which allow proliferation of cells comprising said Tcm phenotype further comprise IL-7 and/or IL-21. 
     
     
         5 . An isolated population of cells comprising non-graft versus host (GVHD) inducing anti-third party cells having a central memory T-lymphocyte (Tcm) phenotype, said Tcm phenotype comprising a CD8 + /CD62L + /CD45RO+ signature and wherein at least 50% of the isolated population of cells have said signature, said cells being tolerance-inducing cells and capable of homing to the lymph nodes following transplantation, generated according to the method of  claim 1 . 
     
     
         6 . A method of treating a disease in a subject in need thereof, the method comprising:
 (a) transplanting a cell or tissue graft to the subject; and   (b) administering to the subject a therapeutically effective amount of the isolated population of cells of  claim 5 .   
     
     
         7 . The method of  claim 6 , wherein said disease is selected from the group consisting of a malignant disease and a disease associated with transplantation of a graft. 
     
     
         8 . The method of  claim 7 , wherein said malignant disease comprises a malignancy of hematopoietic or lymphoid tissues. 
     
     
         9 . The method of  claim 7 , wherein said malignant disease comprises a lymphoma or a leukemia. 
     
     
         10 . The method of  claim 6 , where said graft comprises immature hematopoietic cells. 
     
     
         11 . The method of  claim 6 , further comprising administering at least one immunosuppressant drug to the subject. 
     
     
         12 . The method of  claim 6 , where said subject is further conditioned under sublethal, lethal or supralethal conditioning prior to step (a). 
     
     
         13 . The method of  claim 6 , where step (a) and step (b) are effected concomitantly. 
     
     
         14 . The method of  claim 6 , where step (b) is effected prior to step (a). 
     
     
         15 . The method of  claim 6 , where step (b) is effected one day after step (a). 
     
     
         16 . The method of  claim 6 , where said subject is a human subject.