Anti-Tumour Response to Modified Self-Epitopes

Abstract

Anti-tumour immune responses to modified self-epitopes. The present invention relates to the use of tumour-associated epitopes in medicine and in particular in the treatment of cancer. The epitopes stimulate an immune reaction against the tumour and have a modification selected from determination of arginine to citrulline, nitration of tyrosine, oxidation of tryptophan and deamination of glutamine or asparagine. The invention also relates to nucleic acids comprising sequences that encode such epitopes for use in the treatment of cancer.

1 . A tumour-associated epitope which stimulates an immune reaction against the tumour, the epitope having a modification selected from determination of arginine to citrulline, wherein the epitope is derived from cytokeratin 8. 
     
     
         2 . The epitope of  claim 1 , wherein the epitope comprises a sequence selected from: 
       
         
           
                 
                 
               
                     
                   (SEQ ID NO: 6) 
                 
                     
                   EIRELQSQ, 
                 
                     
                     
                 
                     
                   (cytokeratin 8 229-247) 
                 
                     
                   (SEQ ID NO: 7) 
                 
                     
                   EE EIRELQSQI SDTSVVLS, 
                 
                     
                     
                 
                     
                   (SEQ ID NO. 8) 
                 
                     
                   AKQDMARQLREYQEL, 
                 
                     
                     
                 
                     
                   (cytokeratin 8: 363-382) 
                 
                     
                   (SEQ ID NO: 9) 
                 
                     
                     AKQDMARQLREYQEL MNVKL, 
                 
                     
                     
                 
                     
                   (SEQ ID NO: 10) 
                 
                     
                   AKQDMARQ, 
                 
                     
                     
                 
                     
                   (cytokeratin 8: 360-378) 
                 
                     
                   (SEQ ID NO: 11) 
                 
                     
                   LQR AKQDMARQ LREYQELM, 
                 
                     
                     
                 
                     
                   (SEQ ID NO: 12) 
                 
                     
                   ISSSSFSRV, 
                 
                     
                     
                 
                     
                   (cytokeratin 8: 29-44) 
                 
                     
                   (SEQ ID NO: 13) 
                 
                     
                   PGSR ISSSSFSRV GSS, 
                 
                     
                     
                 
                     
                   (SEQ ID NO: 14) 
                 
                     
                   PRAFSSRS, 
                 
                     
                     
                 
                     
                   (cytokeratin 8: 13-30) 
                 
                     
                   (SEQ ID NO: 15) 
                 
                     
                   STSG PRAFSSRS YTSGPG, 
                 
                     
                     
                 
                     
                   (SEQ ID NO: 16) 
                 
                     
                   EAALQRAKQ, 
                 
                     
                     
                 
                     
                   (cytokeratin 8: 355-371) 
                 
                     
                   (SEQ ID NO: 17) 
                 
                     
                   EL EAALQRAKQ DMARQL, 
                 
                     
                     
                 
                     
                   (SEQ ID NO: 18) 
                 
                     
                   LEVDPNIQAVRTQE 
                 
                     
                   and, 
                 
                     
                     
                 
                     
                   (cytokeratin 8: 78-95) 
                 
                     
                   (SEQ ID NO: 19) 
                 
                     
                     LEVDPNIQAVRTQE KEQI, 
                 
             
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
               
            
           
         
         wherein one or more of the R residues is substituted for citrulline. 
       
     
     
         3 . A method of treating cancer in a patient comprising administering to the patient an effective amount of an epitope of  claim 1 , wherein the cancer is melanoma, breast, endometrial, colorectal or ovarian cancer. 
     
     
         4 . The method of  claim 3 , wherein the patient is a human.