Plif multimeric peptides and uses thereof

Abstract

Provided is a multimeric peptide comprising at least two peptide monomers linked to one another, each of the at least two peptide monomers comprising at least 6 consecutive amino acids from the amino acid sequence as set forth in SEQ ID NO: 1, wherein the at least two peptide monomers are each no longer than 30 amino acids, wherein the multimeric peptide is capable of reducing binding of Placenta Immunomodulatory Factor (PLIF) to human leukocytes.

What is claimed is: 
     
         1 . A multimeric peptide comprising at least two peptide monomers linked to one another, each of said at least two peptide monomers comprising at least 6 consecutive amino acids from the amino acid sequence as set forth in SEQ ID NO: 1, wherein said at least two peptide monomers are each no longer than 30 amino acids, wherein the multimeric peptide is capable of reducing binding of Placenta Immunomodulatory Factor (PLIF) to human leukocytes. 
     
     
         2 . The multimeric peptide of  claim 1 , wherein the peptide is capable of increasing INF-γ secretion from activated leukocytes. 
     
     
         3 . The multimeric peptide of  claim 1 , being a dimer. 
     
     
         4 . The multimeric peptide of  claim 1 , wherein each of said at least two peptide monomers comprise no more than 15 consecutive amino acids from the amino acid sequence as set forth in SEQ ID NO: 1. 
     
     
         5 . The multimeric peptide of  claim 1 , wherein each of said at least two peptide monomers the amino acid sequence as set forth in SEQ ID NO: 1. 
     
     
         6 . The multimeric peptide of  claim 1 , wherein said at least two peptide monomers comprise an identical amino acid sequence. 
     
     
         7 . The multimeric peptide of  claim 1 , wherein each of said at least two peptide monomers is attached to a Cysteine (Cys) residue. 
     
     
         8 . The multimeric peptide of  claim 7 , wherein the caboxy end of said at least two peptide monomers is attached to said Cys residue. 
     
     
         9 . The multimeric peptide of  claim 8 , wherein each of said at least two peptide monomers comprise the amino acid sequence as set forth in SEQ ID NO: 101. 
     
     
         10 . The multimeric peptide of  claim 1 , wherein each of said two peptide monomers are attached via a non-peptide linker. 
     
     
         11 . The multimeric peptide of  claim 7 , wherein said at least two peptide monomers are linked to one another by a disulfide bond. 
     
     
         12 . The multimeric peptide of  claim 11 , wherein said disulfide bond is an intermolecular disulfide bond formed between said Cys residues. 
     
     
         13 . The multimeric peptide of  claim 7 , further comprises a Gly residue connecting said Cys residue to said carboxy end of said at least two peptide monomers. 
     
     
         14 . The multimeric peptide of  claim 1 , wherein each of said two at least two peptide monomers comprises the sequence selected from the group consisting of SEQ ID NOs: 2-7. 
     
     
         15 . The multimeric peptide of  claim 1 , wherein each of said at least two peptide monomers consists of the sequence selected from the group consisting of SEQ ID NOs: 8-13. 
     
     
         16 . The multimeric peptide of  claim 1  comprising at least one synthetic amino acid. 
     
     
         17 . The multimeric peptide of  claim 1 , wherein said at least two peptide monomers comprises least three peptide monomers. 
     
     
         18 . The multimeric peptide of  claim 1 , wherein said at least two peptide monomers are covalently linked to one another. 
     
     
         19 . A pharmaceutical composition comprising the dimeric peptide of  claim 1  as an active agent and a pharmaceutically acceptable carrier. 
     
     
         20 . A pharmaceutical composition comprising the peptide of  claim 17  as an active agent and a pharmaceutically acceptable carrier. 
     
     
         21 . A method of treating a disease associated with a TH2:TH1 bias, the method comprising administering a therapeutically effective amount of the multimeric peptide of  claim 1  to a subject in need thereof, thereby treating the disease associated with a TH2:TH1 bias. 
     
     
         22 . The method of  claim 21 , wherein the disease is cancer. 
     
     
         23 . The method of  claim 22 , wherein said treating results in cancer immunotherapy and long term anti-cancer immunity. 
     
     
         24 . The method of  claim 22 , wherein the cancer is selected from the group consisting of Hodgkin's lymphoma, non-Hodgkin's lymphoma, acute lymphatic leukemia (ALL) and breast cancer. 
     
     
         25 . The method of  claim 21 , wherein the disease is a retrovirally mediated disease. 
     
     
         26 . The method of  claim 25 , wherein the retroviral mediated disease is HIV. 
     
     
         27 . The method of  claim 21 , further comprising detecting a level of PLIF in a sample of the subject prior to the treating. 
     
     
         28 . The method of  claim 21 , further comprising detecting a level of PLIF in a sample of the subject following the treating. 
     
     
         29 . The method of  claim 27 , wherein said sample comprises a tumor sample or a blood sample. 
     
     
         30 . The method of  claim 27 , wherein said detecting is effected on the protein level. 
     
     
         31 . The method of  claim 27 , wherein said detecting is effected on the polynucleotide level. 
     
     
         32 . An isolated peptide comprising at least 6 consecutive amino acids and no more than 30 amino acids from the amino acid sequence as set forth in SEQ ID NO: 1, wherein when linked to a second peptide comprising at least 6 consecutive amino acids and no more than 30 amino acids from the amino acid sequence as set forth in SEQ ID NO: 1 as a dimer, said dimer is capable of reducing binding of Placenta Immunomodulatory Factor (PLIF) to human leukocytes. 
     
     
         33 . A method of generating the dimeric peptide of  claim 1 , the method comprising linking two isolated peptides, which each of said at least two isolated peptides comprise at least 6 consecutive amino acids and no more than 30 amino acids from the amino acid sequence as set forth in SEQ ID NO: 1, thereby generating the dimeric peptide of  claim 1 . 
     
     
         34 . An isolated antibody which binds to the multimeric peptide of  claim 1 , wherein the affinity of the antibody for the multimeric peptide is higher than the affinity of the antibody for C48 under identical conditions.