Lytic-peptide-her2/neu (human epidermal growth factor receptor 2) ligand conjugates and methods of use

Abstract

The invention relates to conjugates that bind to Her2/neu, methods of using conjugates that bind to Her2/neu and methods of treating undesirable or aberrant cell proliferation or hyperproliferative disorders, such as tumors, cancers, neoplasia and malignancies that express Her2/neu.

What is claimed: 
     
         1 . A conjugate comprising:
 a. a first ligand that binds Her2/neu;   b. a first lytic peptide; and   c. a first linker;
 wherein the first ligand and the first lytic peptide are joined by the first linker, and the first ligand is positioned at an N-terminus relative to the first lytic peptide, or the first ligand is position at a C-terminus relative to the first lytic peptide. 
   
     
     
         2 . The conjugate of  claim 1 , wherein first lytic peptide comprises an amino acid sequence selected from the group consisting of KFAKFAKKFAKFAKK (SEQ ID NO. 1), KFAKFAKKFAKFAKKF (SEQ ID NO. 2), KFAKFAKKFAKFAKKFA (SEQ ID NO. 3), KFAKFAKKFAKFAKKFAK (SEQ ID NO. 4), KFAKFAKKFAKFAKKFAKF (SEQ ID NO. 5) and KFAKFAKKFAKFAKKFAKFA (SEQ ID NO. 6). 
     
     
         3 . The conjugate of  claim 1 , wherein the first ligand comprises an antibody or antigen binding fragment thereof. 
     
     
         4 . The conjugate of  claim 1 , wherein the first ligand comprises an affibody. 
     
     
         5 . The conjugate of  claim 1 , wherein the first linker comprises a peptide comprising an N-terminus and a C-terminus. 
     
     
         6 . The conjugate of  claim 5 , wherein the peptide sequence is GS, GSSG, GGGGG, or NRVRRS. 
     
     
         7 . The conjugate of  claim 5 , wherein the first linker comprises of a length between 2 and 20 amino acids. 
     
     
         8 . The conjugate of  claim 5 , wherein the N-terminus of the first linker is joined to the first ligand and the C-terminus of the first linker is joined to the first lytic peptide. 
     
     
         9 . The conjugate of  claim 5 , wherein the N-terminus of the first linker is joined to the first lytic peptide and the C-terminus of the first linker is joined to the first ligand. 
     
     
         10 . The conjugate of  claim 1 , further comprising a second lytic peptide and a second linker, wherein the second linker joins the second lytic peptide to the first ligand. 
     
     
         11 . The conjugate of  claim 10 , wherein the first lytic peptide and the second lytic peptide independently comprise an amino acid sequence selected from the group consisting of KFAKFAKKFAKFAKK (SEQ ID NO. 1), KFAKFAKKFAKFAKKF (SEQ ID NO. 2), KFAKFAKKFAKFAKKFA (SEQ ID NO. 3), KFAKFAKKFAKFAKKFAK (SEQ ID NO. 4), KFAKFAKKFAKFAKKFAKF (SEQ ID NO. 5) and KFAKFAKKFAKFAKKFAKFA (SEQ ID NO. 6). 
     
     
         12 . The conjugate of  claim 1 , further comprising a second lytic peptide and a second linker, wherein the second linker joins the second lytic peptide to the first lytic peptide. 
     
     
         13 . The conjugate of  claim 12 , wherein the first lytic peptide and the second lytic peptide independently comprise an amino acid sequence selected from the group consisting of KFAKFAKKFAKFAKK (SEQ ID NO. 1), KFAKFAKKFAKFAKKF (SEQ ID NO. 2), KFAKFAKKFAKFAKKFA (SEQ ID NO. 3), KFAKFAKKFAKFAKKFAK (SEQ ID NO. 4), KFAKFAKKFAKFAKKFAKF (SEQ ID NO. 5) and KFAKFAKKFAKFAKKFAKFA (SEQ ID NO. 6).