Cell Penetrating Peptides and Complexes Comprising the Same

Abstract

The present invention provides a cell penetrating peptide derived from ZEBRA, which is optionally linked to a cargo molecule, such as at least one antigen or antigenic epitope. The present invention also provides a complex comprising the cell penetrating peptide and the cargo molecule. In particular, compositions, such as a pharmaceutical compositions and vaccines are provided, which may be useful for example in the prevention and/or treatment of a diseases and/or a disorder including cancer, hematological disorders, infectious diseases, autoimmunity disorders and transplant rejections.

1 . A cell penetrating peptide comprising an amino acid sequence sharing at least 80% sequence identity with SEQ ID NO: 1, wherein the amino acid sequence sharing at least 80% sequence identity with SEQ ID NO: 1:
 provides cell penetrating functionality;   has a serine at position 12; and   has a length of at least 36 amino acids in total.   
     
     
         2 .- 4 . (canceled) 
     
     
         5 . The cell penetrating peptide according to  claim 1 , wherein the cell penetrating peptide consists of an amino acid sequence according to SEQ ID NO: 1. 
     
     
         6 . A complex comprising the cell penetrating peptide according to  claim 1  and a cargo molecule, wherein the cell penetrating peptide according to  claim 1  and the cargo molecule are preferably covalently linked. 
     
     
         7 . The complex according to  claim 6 , wherein the cargo molecule is selected from the group consisting of: (i) a peptide, a polypeptide, or a protein; (ii) a polysaccharide; (iii) a lipid; (iv) a lipoprotein; (v) a glycolipid; (vi) a nucleic acid; (vii) a small molecule drug or toxin; and (viii) an imaging or contrast agent. 
     
     
         8 . (canceled) 
     
     
         9 . The complex according to  claim 6 , wherein the cargo molecule is at least one antigen or antigenic epitope. 
     
     
         10 . The complex according to  claim 9 , wherein the at least one antigen or antigenic epitope comprises or consists of at least one pathogen epitope and/or at least one tumor epitope, preferably the at least one antigen or antigenic epitope comprises or consists of at least one tumor epitope. 
     
     
         11 . (canceled) 
     
     
         12 . The complex according to  claim 9 , wherein the complex comprises more than one antigen or antigenic epitope, in particular 2, 3, 4, 5, 6, 7, 8, 9, 10 or more antigens or antigenic epitopes. 
     
     
         13 . (canceled) 
     
     
         14 . (canceled) 
     
     
         15 . The complex according to  claim 9 , wherein the complex further comprises a TLR peptide agonist. 
     
     
         16 . The complex according to  claim 15 , wherein the TLR peptide agonist is a TLR2, TLR4 and/or TLR5 peptide agonist, preferably a TLR2 peptide agonist and/or a TLR4 peptide agonist. 
     
     
         17 . (canceled) 
     
     
         18 . The complex according to  claim 16 , wherein the TLR peptide agonist comprises or consists of an amino acid sequence according to SEQ ID NO: 5 or a functional sequence variant thereof. 
     
     
         19 . (canceled) 
     
     
         20 . (canceled) 
     
     
         21 . The complex according to  claim 15 , wherein the complex is a recombinant polypeptide or a recombinant protein and the cell penetrating peptide, the at least one antigen or antigenic epitope and the TLR peptide agonist are positioned in N-terminal→C-terminal direction of the main chain of said complex in the order:
 (a) cell penetrating peptide—at least one antigen or antigenic epitope—TLR peptide agonist; or 
 (b) TLR peptide agonist—cell penetrating peptide—at least one antigen or antigenic epitope, 
 wherein the cell penetrating peptide, the at least one antigen or antigenic epitope and the TLR peptide agonist may be optionally linked by a further component, in particular by a linker or a spacer. 
 
     
     
         22 . (canceled) 
     
     
         23 . A nucleic acid encoding the cell penetrating peptide according to  claim 1 . 
     
     
         24 . A vector comprising the nucleic acid according to  claim 23 . 
     
     
         25 . A host cell comprising the vector according to  claim 24 . 
     
     
         26 . (canceled) 
     
     
         27 . A cell loaded the complex according to  claim 6 . 
     
     
         28 . The cell according to  claim 27 , wherein said cell is an antigen presenting cell, preferably a dendritic cell. 
     
     
         29 . (canceled) 
     
     
         30 . (canceled) 
     
     
         31 . A pharmaceutical composition comprising at least one complex according to  claim 6  and a pharmaceutically acceptable carrier. 
     
     
         32 .- 37 . (canceled) 
     
     
         38 . A method of preventing and/or treating of a diseases and/or a disorder including cancer, hematological disorders, infectious diseases, autoimmunity disorders and transplant rejections in a subject, the method comprising administering to the subject a complex according to  claim 6 . 
     
     
         39 . The method of  claim 38 , wherein the disease to be prevented and/or treated is cancer and/or a hematological disorder, preferably a malignant neoplasm of the brain or a malignant neoplasm of lymphoid, hematopoietic and related tissue, most preferably glioblastoma. 
     
     
         40 . (canceled) 
     
     
         41 . The nucleic acid according to  claim 23  encoding a complex comprising the cell penetrating peptide and a cargo molecule, wherein the complex is a recombinant peptide, a recombinant polypeptide or a recombinant protein.