Short beta-defensin-derived peptides

Abstract

The invention is directed to β-defensin-derived peptides and their use in modulating the activity of hematopoietic cells, particularly hematopoietic stem cells and progenitor cells. Specifically, the invention provides compositions and methods useful for promoting mobilization and transplantation of hematopoietic stem cells and progenitor cells. The invention further provides compositions and methods useful in the treatment of cancer.

What is claimed is: 
     
         1 . A method of increasing cytokine-induced hematopoietic precursor cell mobilization, comprising administering to a subject an effective amount of a cytokine that stimulates mobilization of hematopoietic cells and an isolated peptide having an N-terminus and a C-terminus selected from the group consisting of:
 (a) RGRKCCRRKK (TL-1, SEQ ID NO: 1); and   (b) SGRKCCRKKK (AK-1, SEQ ID NO: 2), thereby increasing the cytokine-induced hematopoietic precursor cell mobilization in the subject.   
     
     
         2 . The method of  claim 1 , wherein said peptide is RGRKCCRRKK (TL-1, SEQ ID NO: 1). 
     
     
         3 . The method of  claim 1 , wherein said peptide is SGRKCCRKKK (AK-1, SEQ ID NO: 2). 
     
     
         4 . The method of  claim 1 , wherein said administering said cytokine is concurrent with said administering said peptide. 
     
     
         5 . The method of  claim 1 , wherein said administering said cytokine is sequential with said administering said peptide. 
     
     
         6 . The method of  claim 1 , wherein said cytokine comprises G-CSF. 
     
     
         7 . The method of  claim 1 , wherein said subject is in need of hematopoietic stem and progenitor cells harvesting. 
     
     
         8 . The method of  claim 1 , wherein said subject is in need of bone marrow transplantation. 
     
     
         9 . The method of  claim 1 , wherein said subject has a disorder, in which cells that express CXCR4, e.g. cancer cells, contribute to the etiology or pathology of the disorder. 
     
     
         10 . The method of  claim 1 , wherein said subject has cancer. 
     
     
         11 . A kit comprising a cytokine that stimulates mobilization of hematopoietic cells and an isolated peptide having an N-terminus and a C-terminus selected from the group consisting of: 
       
         
           
                 
                 
               
                     
                   (TL-1, SEQ ID NO: 1) 
                 
                     
                   (a) RGRKCCRRKK;  
                 
                     
                   and 
                 
                     
                     
                 
                     
                   (AK-1, SEQ ID NO: 2) 
                 
                     
                   (b) SGRKCCRKKK. 
                 
             
                
                
                
                
                
                
               
            
           
         
       
     
     
         12 . The kit of  claim 11 , wherein said peptide is RGRKCCRRKK (TL-1, SEQ ID NO: 1). 
     
     
         13 . The kit of  claim 11 , wherein said peptide is SGRKCCRKKK (AK-1, SEQ ID NO: 2). 
     
     
         14 . The kit of  claim 11 , wherein said cytokine comprises G-CSF.