Methods for Manipulating Phagocytosis Mediated by CD47

Abstract

Methods are provided to manipulate phagocytosis of cells, including hematopoietic cells, e.g. circulating hematopoietic cells, bone marrow cells, acute leukemia cells, etc.; and solid tumor cells. In some embodiments of the invention the circulating cells are hematopoietic stem cells, or hematopoietic progenitor cells, particularly in a transplantation context, where protection from phagocytosis is desirable. In other embodiments the circulating cells are leukemia cells, particularly acute myeloid leukemia (AML), where increased phagocytosis is desirable.

What is claimed is: 
     
         1 . A method for treating a human subject with acute myeloid leukemia (AML), the method comprising:
 administering to the human subject an antibody or a fragment thereof that specifically binds to CD47 of an AML stem cell and prevents the CD47 from binding to a SIRPα receptor of a macrophage or a dendritic cell.   
     
     
         2 . The method of  claim 1 , wherein the antibody or the fragment thereof is administered in a dose capable of depleting a plurality of the AML stem cell. 
     
     
         3 . The method of  claim 2 , wherein the plurality of the AML stem cell is depleted. 
     
     
         4 . The method of  claim 1 , wherein the antibody or the fragment thereof is administered in a dose capable of inducing phagocytosis of a plurality of the AML stem cell. 
     
     
         5 . The method of  claim 4 , wherein phagocytosis of the plurality of the AML stem cell is induced. 
     
     
         6 . The method of  claim 1 , wherein the antibody is a humanized antibody or a chimeric antibody. 
     
     
         7 . The method of  claim 1 , wherein the antibody is a monoclonal antibody. 
     
     
         8 . The method of  claim 1 , wherein the antibody is a bispecific antibody. 
     
     
         9 . The method of  claim 1 , wherein the antibody or the fragment thereof is a conjugate. 
     
     
         10 . The method of  claim 9 , wherein the antibody or the fragment thereof is conjugated to at least one of: a radioactive isotope, a chemotherapeutic agent, and a toxin. 
     
     
         11 . The method of  claim 1 , further comprising:
 administering to the human subject a chemotherapeutic drug.   
     
     
         12 . The method of  claim 1 , wherein the antibody is B6H12, a humanized form thereof, or a chimeric form thereof. 
     
     
         13 . A method for treating a human subject with leukemia, the method comprising:
 administering to the human subject an antibody or a fragment thereof that specifically binds to CD47 of a leukemia stem cell and prevents the CD47 from binding to a SIRPα receptor of a macrophage or a dendritic cell.   
     
     
         14 . The method of  claim 13 , wherein the antibody or the fragment thereof is administered in a dose capable of depleting a plurality of the leukemia stem cell. 
     
     
         15 . The method of  claim 14 , wherein the plurality of the leukemia stem cell is depleted. 
     
     
         16 . The method of  claim 13 , wherein the antibody or the fragment thereof is administered in a dose capable of inducing phagocytosis of a plurality of the leukemia stem cell. 
     
     
         17 . The method of  claim 16 , wherein phagocytosis of the plurality of the leukemia stem cell is induced. 
     
     
         18 . The method of  claim 13 , wherein the antibody is a humanized antibody or a chimeric antibody. 
     
     
         19 . The method of  claim 13 , wherein the antibody is a monoclonal antibody. 
     
     
         20 . The method of  claim 13 , wherein the antibody is a bispecific antibody. 
     
     
         21 . The method of  claim 13 , wherein the antibody or the fragment thereof is a conjugate. 
     
     
         22 . The method of  claim 21 , wherein the antibody or the fragment thereof is conjugated to at least one of: a radioactive isotope, a chemotherapeutic agent, and a toxin. 
     
     
         23 . The method of  claim 13 , further comprising:
 administering to the human subject a chemotherapeutic drug.   
     
     
         24 . The method of  claim 13 , wherein the antibody is B6H12, a humanized form thereof, or a chimeric form thereof. 
     
     
         25 . The method of  claim 13 , wherein the leukemia is acute myeloid leukemia (AML) or acute lymphoblastic leukemia (ALL).