Enhancement of allogeneic hematopoietic stem cell transplantation

摘要

Methods and compositions are provided to augment the conversion of mixed hematopoietic cell chimerism to complete donor cell chimerism following allogeneic hematopoietic cell transplantation (HCT), where such transplantation may be utilized for treatment of cancer such as leukemia and lymphoma or for other conditions requiring reconstitution of the hematopoietic system, e.g. treatment of anemias, thalassemias, autoimmune conditions, and the like. The present invention improves on conventional DLI by utilizing a composition of substantially purified donor memory CD8+ T cells as DLI following allogeneic HCT, where the cells are administered at a suitable time following transplantation. The methods provide for a more complete donor chimerism, and have the further benefit of killing tumor cells without GVHD. The memory CD8+ T cells may include one or both of central and effector memory T cells, usually both.

主权项

1. A method of enhancing allogeneic hematopoietic cell transplantation and anti-tumor activity in a human, the method comprising:
preventing cancer relapse by administering to the human previously treated for the cancer with an allogeneic hematopoietic cell transplantation a dose of at least 1×106 and at least 80% pure donor-derived memory CD8+ T cells selected for with an affinity agent specific for CD8, and comprising central and effector memory T cells that are effective to enhance killing of residual cancer cells in the human in the absence of graft versus host disease, wherein the donor-derived memory T cells are selected from CD8+CD45RA− and/or CD8+CD45RO+, wherein the memory CD8+ T cells are administered to the human at least two months after the allogeneic hematopoietic cell transplantation and prior to relapse, and wherein the dose of donor-derived memory T cells enhances complete chimerism.