Chimeric polypeptide comprising the fragment b of shiga toxin and peptides of therapeutic interest

Abstract

The invention pertains to methods for using chimeric polypeptides of the formula: B-X wherein B represents the B fragment of Shiga toxin or a functional equivalent thereof, and X represents one or more polypeptides of therapeutic significance. Compositions for therapeutic use comprising the polypeptide B-X are also included.

1 - 18 . (canceled) 
     
     
         19 . A polynucleotide coding for the chimeric polypeptide:
   B-X   wherein B is the B fragment of Shiga toxin or a B toxin fragment that binds to a globotriaosylceramide (Gb3) receptor; and   
       X represents one or more polypeptides of therapeutic significance, wherein said polypeptides are compatible with retrograde transport mediated by B to ensure processing or correct addressing of X. 
     
     
         20 . The polynucleotide according to  claim 19 , wherein X is an epitope which can be presented by the class I major histocompatibility complex. 
     
     
         21 . The polynucleotide according to  claim 19 , wherein X is an epitope of a polypeptide or protein wherein the expression of said epitope is desired at the surface of cells of the immune system. 
     
     
         22 . The polynucleotide according to  claim 21 , wherein said protein or polypeptide is a cancer cell protein, a viral protein, a viral protein from a cancer or an oncogene. 
     
     
         23 . The polynucleotide according to  claim 22 , wherein said viral protein from a cancer are selected from the group of peptides from E6 proteins of HPV16, peptides from E7 proteins of HPV, peptides from a Hbs protein of HBV, peptides from EBV and peptides from cytomegalovirus. 
     
     
         24 . The polynucleotide according to  claim 19 , wherein X is a human epitope from an autoimmune disease. 
     
     
         25 . The polynucleotide according to  claim 19 , wherein X is a human epitope from an infectious disease. 
     
     
         26 . The polynucleotide according to  claim 25 , wherein the human epitope from an infectious disease is an epitope from HTLV-I-associated myelopathy/tropical spastic paraparesis. 
     
     
         27 . The polynucleotide according to  claim 19 , wherein X is an epitope derived from melanoma cell proteins. 
     
     
         28 . The polynucleotide according to  claim 27 , wherein the melanoma cell proteins are selected from the group of BAGE from tyrosinase, GAGE from gp75, tyrosinase, p15 from A/MART-1 melanoma, MAGE-1 and MAGE-3. 
     
     
         29 . The polynucleotide according to  claim 19 , wherein X is a parasitic antigen, a bacterial antigen or a cancerogenic viral protein. 
     
     
         30 . The polynucleotide according to  claim 19 , wherein X is a polypeptide which can restore or activate an intracellular transport function by interacting with proteins of the cellular machinery, wherein said polypeptide competes in the endoplasmic reticulum with a mutated form of a protein involved in intracellular transport or by supplementing a function, which is deficient in said transport. 
     
     
         31 . The polynucleotide according to  claim 30 , wherein X is the domain of interaction of a cystic fibrosis transmembrane regulator (CFTR) protein with calnexin. 
     
     
         32 . A composition comprising the polynucleotide coding for the polypeptide according to  claim 19 . 
     
     
         33 . The composition according to  claim 32 , wherein said composition stimulates the immune defenses of the organism towards viral, parasitic, infectious or cancerous antigens.