Methods for obtaining a therapeutically effective amount of hematopoietic precursor cells and long term engraftment thereof

Abstract

The present invention is directed to novel therapeutic uses of T-140 analog peptides and compositions comprising same. Specifically, the invention provides compositions and methods useful for providing improved bone marrow transplantation and in the treatment of other conditions wherein bone marrow depletion or suppression is involved.

1 . A pharmaceutical composition comprising as active ingredients effective amounts of at least one cytokine that stimulates mobilization of hematopoietic cells and a peptide having an amino acid sequence as set forth in SEQ ID NO:1 or an analog or derivative thereof. 
     
     
         2 . A composition according to  claim 1 , wherein the cytokine is granulocyte-colony stimulating factor (G-CSF). 
     
     
         3 . The composition of  claim 1 , wherein the analog or derivative has an amino acid sequence as set forth in formula (I) or a salt thereof: 
       
         
           
                 
                 
               
                     
                   (I) 
                 
                     
                   1  2  3  4   5  6  7  8 9 10 11 12  13 14 
                 
                     
                   A 1 -A 2 -A 3 -Cys-Tyr-A 4 -A 5 -A 6 -A 7 -A 8 -A 9 -A 10 -Cys-A 11   
                 
             
                
                
                
               
            
           
         
         wherein: 
         A 1  is an arginine, lysine, ornithine, citrulline, alanine or glutamic acid residue or a N-α-substituted derivative of these amino acids, or A 1  is absent; 
         A 2  represents an arginine or glutamic acid residue if A 1  is present, or A 2  represents an arginine or glutamic acid residue or a N-α-substituted derivative of these amino acids if A 1  is absent; 
         A 3  represents an aromatic amino acid residue; 
         A 4 , A 5  and A 9  each independently represents an arginine, lysine, ornithine, citrulline, alanine or glutamic acid residue; 
         A 6  represents a proline, glycine, ornithine, lysine, alanine, citrulline, arginine or glutamic acid residue; 
         A 7  represents a proline, glycine, ornithine, lysine, alanine, citrulline or arginine residue; 
         A 8  represents a tyrosine, phenylalanine, alanine, naphthylalanine, citrulline or glutamic acid residue; 
         A 10  represents a citrulline, glutamic acid, arginine or lysine residue; 
         A 11  represents an arginine, glutamic acid, lysine or citrulline residue wherein the C-terminal carboxyl may be derivatized; 
         and the cysteine residue of the 4-position or the 13-position can form a disulfide bond, and the amino acids can be of either L or D form. 
       
     
     
         4 . The composition of  claim 2 , wherein the peptide is selected from the group consisting of SEQ ID NOS:1-72. 
     
     
         5 . The composition of  claim 4 , wherein the peptide is selected from the group consisting of SEQ ID NOS:2-4, 10, 45, 46, 51-56, 65, 66, 68, 70 and 71. 
     
     
         6 . The composition of  claim 4 , wherein said peptide is as set forth in SEQ ID NO: 1 and said cytokine is G-CSF. 
     
     
         7 . A pharmaceutical kit containing: i) at least one cytokine that stimulates mobilization of hematopoietic cells and ii) a peptide having an amino acid sequence as set forth in SEQ ID NO:1 or an analog or derivative thereof. 
     
     
         8 . The kit of  claim 7  containing: i) G-CSF and ii) a peptide having an amino acid sequence as set forth in SEQ ID NO:1 or an analog or derivative thereof.