Minigene

Abstract

The present invention provides minigenes suitable as a prophylactic or therapeutic vaccine against conditions such as cancer, infectious diseases or autoimmune diseases, and pharmaceutical compositions comprising the minigene. The minigenes of the present invention comprise (a) a human tissue plasminogen signal peptide; (b) at least one T-cell epitope; and (c) an E. coli heat labile enterotoxin B subunit; wherein the at least one T-cell epitope is linked to the rest of the minigene, and to any other epitopes, by furin sensitive linkers. In some embodiments of the invention, the minigene comprises T-cell epitopes from one or more of CEA, her-2/neu and hTERT. Also provided herein are immunogenic peptide epitopes of CEA, her-2/neu and hTERT, as well as immunogenic peptide analogs, and pharmaceutical compositions and vaccines comprising one or more of said peptides and analogs for prophylaxis and/or treatment of cancer or other disorder. Methods of inducing an immune response in a patient, in addition to methods of treatment using the minigenes, immunogenic peptides, and peptide analogs disclosed herein are also provided.

1 . A minigene comprising:
 (a) a human tissue plasminogen signal peptide;   (b) at least one T-cell epitope; and   (c) an  E. coli  heat labile enterotoxin B subunit; wherein   (d) the at least one T-cell epitope is linked to the rest of the minigene, and to any other epitopes, by furin sensitive linkers having the sequence RxKR or RxRR where x is any amino acid.   
     
     
         2 . A minigene according to  claim 1  wherein the furin sensitive linkers have the sequence REKR. 
     
     
         3 . A minigene according to  claim 1  wherein the T-cell epitope is an immunogenic analogue of a naturally occurring epitope. 
     
     
         4 . A minigene according to  claim 1 , wherein the T-cell epitope is from a microbial or tumour associated antigen or from the variable domain of an autoantibody. 
     
     
         5 . A minigene according to  claim 1  wherein the T-cell epitope is restricted by an HLA allele. 
     
     
         6 . A minigene according to  claim 5  comprising from two to twenty epitopes. 
     
     
         7 . A minigene according to  claim 4  wherein the at least one T-cell epitope is from one or more of CEA, her-2/neu and hTERT. 
     
     
         8 . A minigene according to  claim 5  having more than one T-cell epitope restricted by more than one HLA allele. 
     
     
         9 . A minigene according to  claim 6  wherein at least one of the T-cell epitopes is repeated. 
     
     
         10 . A minigene according to  claim 1  comprising furin-sensitive linkers having at least two different sequences. 
     
     
         11 . A minigene according  claim 1  further comprising a T-helper epitope. 
     
     
         12 . A minigene according to  claim 12  wherein the T-helper epitope is tetanus toxin-derived universal helper peptide p2 or p30. 
     
     
         13 . A pharmaceutical composition comprising a minigene according to  claim 1  and a pharmaceutically acceptable excipient adjustment. 
     
     
         14 - 15 . (canceled) 
     
     
         16 . A method of treatment of a subject suffering from or prone to cancer, an infectious disease or an autoimmune disease which comprises administering to that subject a therapeutically or prophylactically effective amount of a minigene of  claim 1 . 
     
     
         17 . The pharmaceutical composition of  claim 13 , wherein the at least one T-cell epitope is from one or more of CEA, her-2/neu and hTERT. 
     
     
         18 . The minigene according to  claim 3 , wherein the furin sensitive linkers have the sequence REKR. 
     
     
         19 . The minigene according to  claim 18 , wherein the T-cell epitope is restricted by an HLA allele. 
     
     
         20 . The minigene according to  claim 19 , wherein the at least one T-cell epitope is from one or more of CEA, her-2/neu and hTERT. 
     
     
         21 . The pharmaceutical composition of  claim 13 , further comprising an adjuvant. 
     
     
         22 . The minigene according to  claim 6 , wherein the epitopes are from more than one antigen.