Patent ID: 9738872
Date: 2017-08-22
CPC Classifications: A61K,A61P,C12N

Claim:
1. An in vitro method of generating a modified population of cells comprising: (a) contacting peripheral blood mononuclear cells (PBMC) with one or more third party antigens in a culture medium deprived of cytokines for at least 2 days thereby eliminating graft-versus-host (GVH) reactive cells, wherein said third party antigens are selected from a group consisting of third party cells, a cell antigen, a viral antigen, a bacterial antigen, a protein extract, a purified protein and a synthetic peptide presented by autologous presenting cells, non-autologous presenting cells or on an artificial vehicle, allogeneic stimulatory cells, cells purified from peripheral blood lymphocytes, spleen or lymph nodes, cytokine-mobilized PBLs and in vitro expanded antigen-presenting dendritic cells (APC); and (b) culturing cells produced by step (a) in the presence of IL-15 in a culture medium free of said third party antigens for at least 14 days, wherein the modified cell population produced by step (b) has a central memory T-lymphocyte (Tcm) phenotype comprising a CD8+, CD62L+, CD45RA−, CD45RO+ signature and is free of GVH reactive cells, and wherein at least 50% of said modified cell population has said signature, is tolerance-inducing, and is capable of homing to lymph nodes following transplantation.