Anti third party central memory t cells, methods of producing same and use of same in transplantation and disease treatment

A method of generating an isolated population of cells comprising anti-third party cells having a central memory T-lymphocyte (Tcm) phenotype, said cells being tolerance-inducing cells and/or endowed with graft-versus-leukemia (GVL) activity, and capable of homing to the lymph nodes following transplantation, the method comprising:

• (a) treating non-adherent peripheral blood mononuclear cells (PBMC) with an agent capable of depleting CD4+ and/or CD56+ cells so as to obtain CD8+ T cells;
• (b) contacting said CD8+ T cells with third party dendritic cells in the presence of IL-21 for 12 hours to 5 days so as to allow enrichment of antigen reactive cells;
• (c) culturing said cells resulting from step (b) with said third party dendritic cells in the presence of IL-21, IL-15 and IL-7 for 12 hours to 3 days;
• and
• (d) culturing said cells resulting from step (c) in the presence of IL-21, IL-15 and IL-7 in an antigen free environment for 5-20 days so as to allow proliferation of cells comprising said central memory T-lymphocyte (Tcm) phenotype, thereby generating the isolated population of cells.

A method of generating an isolated population of cells comprising anti-third party cells having a central memory T-lymphocyte (Tcm) phenotype, said cells being endowed with anti-disease activity, and capable of homing to the lymph nodes following transplantation, the method comprising:

• (a) treating non-adherent peripheral blood mononuclear cells (PBMC) with an agent capable of depleting CD4+ and/or CD56+ cells so as to obtain CD8+ T cells;
• (b) contacting said CD8+ T cells with non-syngeneic dendritic cells in the presence of IL-21 for 12 hours to 5 days so as to allow enrichment of antigen reactive cells;
• (c) culturing said cells resulting from step (b) with said non-syngeneic dendritic cells in the presence of IL-21, IL-15 and IL-7 for 12 hours to 3 days;
• and
• (d) culturing said cells resulting from step (c) in the presence of IL-21, IL-15 and IL-7 in an antigen free environment for 5-20 days so as to allow proliferation of cells comprising said central memory T-lymphocyte (Tcm) phenotype, thereby generating the isolated population of cells.