Methods of mobilizing marrow infiltrating lymphocytes and uses thereof

Abstract

Methods are disclosed for the mobilization of marrow infiltrating cells (MILs) using E-selectin antagonists for the treatment of disorders such as cancer. Methods for treating or preventing cancers using MILs mobilized by E-selectin antagonists are further disclosed.

1 - 19 . (canceled) 
     
     
         20 . A composition comprising MILs from a cancer patient that were mobilized out of the bone marrow by at least one E-selectin antagonist;
 wherein the at least one E-selectin antagonist is chosen from   
       
         
           
           
               
               
           
         
       
     
     
         21 . The composition of  claim 20 , wherein the at least one E-selectin antagonist is not used in combination with other agents used to mobilize hematopoietic stem cells. 
     
     
         22 . The composition of  claim 20 , wherein the MILs comprise CD8+ T cells. 
     
     
         23 . The composition of  claim 20 , wherein the MILs comprise naïve CD8+ T cells. 
     
     
         24 . The composition of  claim 20 , wherein the MILs comprise CD8+ T cells and wherein at least 5% of the CD8+ T cells are naïve CD8+ T cells. 
     
     
         25 . The composition of  claim 20 , wherein the MILs comprise CD8+ T cells and wherein at least 10% of the CD8+ T cells are naïve CD8+ T cells. 
     
     
         26 . The composition of  claim 20 , wherein the MILs comprise central memory CD8+ T cells. 
     
     
         27 . The composition of  claim 20 , wherein the MILs comprise CD8+ T cells and wherein at least 35% of the CD8+ T cells are central memory CD8+ T cells. 
     
     
         28 . The composition of  claim 20 , wherein the MILs comprise CD8+ T cells and wherein at least 40% of the CD8+ T cells are central memory CD8+ T cells. 
     
     
         29 . The composition of  claim 20 , wherein the MILs comprise both naïve CD8+ T cells and central memory CD8+ T cells. 
     
     
         30 . The composition of  claim 20 , wherein the MILs comprise CD8+ T cells and wherein at least 5% of the CD8+ T cells are naïve CD8+ T cells and at least 35% of the CD8+ T cells are central memory CD8+ T cells. 
     
     
         31 . The composition of  claim 20 , wherein the MILs comprise CD8+ T cells and wherein at least 10% of the CD8+ T cells are naïve CD8+ T cells and at least 40% of the CD8+ T cells are central memory CD8+ T cells. 
     
     
         32 . The composition of  claim 20 , wherein the MILs comprise CD8+ T cells armed to produce IFNγ following stimulation with a CT-26 tumor antigen. 
     
     
         33 . The composition of  claim 20 , wherein the MILs comprise CD8+ T cells and wherein at least 15% of the CD8+ T cells are armed to produce IFNγ following stimulation with a CT-26 tumor antigen. 
     
     
         34 . The composition of  claim 20 , wherein the MILs comprise CD8+ T cells and wherein at least 20% of the CD8+ T cells are armed to produce IFNγ following stimulation with a CT-26 tumor antigen. 
     
     
         35 . The composition of  claim 20 , wherein the MILs comprise CD8+ T cells and wherein at least 5% of the CD8+ T cells are naïve CD8+ T cells, at least 35% of the CD8+ T cells are central memory CD8+ T cells, and at least 15% of the CD8+ T cells armed to produce IFNγ following stimulation with a CT-26 tumor antigen. 
     
     
         36 . The composition of  claim 20 , wherein the at least one E-selectin antagonist is chosen from 
       
         
           
           
               
               
           
         
       
       and pharmaceutically acceptable salts thereof. 
     
     
         37 . The composition of  claim 20 , wherein the at least one E-selectin antagonist is 
       
         
           
           
               
               
           
         
       
     
     
         38 . The composition of  claim 20 , wherein the at least one E-selectin antagonist is chosen from 
       
         
           
           
               
               
           
         
       
       pharmaceutically acceptable salts thereof. 
     
     
         39 . The composition of  claim 20 , wherein the at least one E-selectin antagonist is