Enhancement of Allogeneic Hematopoietic Stem Cell Transplantation

Abstract

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.

1 . A method of enhancing allogeneic hematopoietic cell transplantation, the method comprising:
 administering to a host mammal following said allogeneic hematopoietic cell transplantation an effective dose of donor-derived memory CD8+ T cells.   
     
     
         2 . The method of  claim 1 , wherein said memory CD8+ T cells are at least 80% the pure. 
     
     
         3 . The method of  claim 2 , wherein said memory CD8+ T cells comprise central and effector memory T cells. 
     
     
         4 . The method of  claim 3 , wherein said cells are CD8 +  and CD44 + . 
     
     
         5 . The method of  claim 4 , wherein said memory T cells are mouse cells. 
     
     
         6 . The method of  claim 3 , wherein said cells are CD8 + CD45RA −  and/or CD8 + CD45RO + . 
     
     
         7 . The method of  claim 6 , wherein said cells are human cells. 
     
     
         8 . The method of  claim 1 , wherein said host mammal has been treated for cancer. 
     
     
         9 . The method of  claim 8 , wherein said dose of memory T cells is effective to enhance killing of residual tumor cells. 
     
     
         10 . The method of  claim 1 , wherein said dose of memory T cells enhances complete chimerism in the absence of graft v host disease.