Combined organ and hematopoietic cells for transplantation tolerance of grafts

摘要

Methods and compositions are provided for combined transplantation of a solid organ and hematopoietic cells to a recipient, where tolerance to the graft is established through development of a persistent mixed chimerism. An individual with persistent mixed chimerism, usually for a period of at least six months, is able to withdraw from the use of immunosuppressive drugs after a period of time sufficient to establish tolerance.

主权项

1. A method for maintaining mixed chimerism for at least six months and withdrawal of immunosuppressive drugs without a rejection episode or graft versus host disease (GVHD) in a recipient of a solid human organ transplantation, wherein a donor of the solid human organ and the recipient are HLA-matched, the method comprising:
administering a pharmaceutically effective dosage of an engineered hematopoietic cell composition to the recipient, wherein the engineered hematopoietic cell composition comprises: greater than 5×105 purified CD34+ cells/kilogram recipient weight and from about 1.5×105 to about 1×1010 CD3+ T cells/kilogram recipient weight, wherein the purified CD34+ cells in the engineered hematopoietic cell composition are purified to a purity of greater than 85%, wherein a concentration of iron associated with the purified CD34+ cells is higher than the concentration of iron associated with CD34+ cells prior to the purification, and wherein the engineered hematopoietic cell composition comprises a ratio of the CD3+ T cells to the purified CD34+ cells of greater than 0.25.