Genetically modified anti-third party central memory t cells and use of same in immunotherapy

A method of generating an isolated cell having a central memory T-lymphocyte (Tcm) phenotype and expressing a heterologous cell surface receptor, said cell being tolerance-inducing cell and capable of homing to the lymph nodes following transplantation, the method comprising:

• (a) depleting CD4+ cells or selecting CD8+ cells from peripheral blood mononuclear cells (PBMC);
• (b) contacting said cells following step (a) with a third party antigen in the presence of IL-21 so as to allow enrichment of antigen reactive cells;
• (c) culturing said cells resulting from step (b) in the presence of IL-21, IL-15 and IL-7 so as to allow proliferation of anti-third party cells comprising said Tcm phenotype;
• and
• (d) transducing said cells during or following said step (b) or (c) with a polynucleotide encoding a cell surface receptor comprising a T cell receptor signaling module and an extracellular domain directed against a disease antigen.