HPV epitopes targeted by T cells infiltrating cervical malignancies for use in vaccines

Abstract

The present invention relates to novel CD4+ and CD8+ T cell epitopes that are specific for HPV-specific E6 and E7 oncoproteins, to peptides comprising these novel T cell epitopes, and to (vaccine) compositions comprising these peptides for use in methods for the prevention and/or treatment of HPV related diseases. Preferred epitopes are recognized by a T cell that infiltrates a cervical neoplastic lesion or by a T cell from a draining lymph node, and are presented by an HLA-DQ or HLA-DP molecule, or an HLA-B.

1 . A peptide for the prevention and/or treatment of an HPV related disease, wherein the peptide has a length of no more than 100, 98, 96, 94, 92 amino acids and comprises at least 19 contiguous amino acids from the amino acid sequence of at least one of an HPV E6 and E7 protein, wherein the contiguous amino acid sequence comprises an epitope that is presented by at least one of an HLA-DQ and HLA-DP molecule and wherein the epitope is not the epitope presented in the context of HLA-DQ2 and consisting of amino acid 35-50 of the HPV16 E7 protein. 
     
     
         2 . A peptide according to  claim 1 , and wherein the contiguous amino acid sequence comprises an epitope that is recognized by a T cell that infiltrates a cervical neoplastic lesion or by a T cell from a draining lymph node. 
     
     
         3 . A peptide according to  claim 1 , wherein the epitope is an epitope of an HPV E6 protein. 
     
     
         4 . A peptide according to  claim 1 , wherein the epitope is an epitope of an HPV serotype 16, 18, 31, 33 or 45, preferably 16, 18, 31 or 33, more preferably 16 or 18. 
     
     
         5 . A peptide according to  claim 1 , wherein the epitope is selected from the group consisting of SEQ ID No.'s 6, 5, 7, 9, 10, 11, 12, 13, 16, 18, 19, 20 and 21. 
     
     
         6 . A petide according to  claim 1 , wherein the length of the contiguous amino acid sequence is 19-45 amino acids, preferably 22-35 amino acids and more preferably 33-35 amino acids. 
     
     
         7 . A peptide for the prevention and/or treatment of an HPV related disease, wherein the peptide has a length of no more than 100 amino acids and comprises at least 19 contiguous amino acids from the amino acid sequence of at least one of an HPV E6 and E7 protein, wherein the contiguous amino acid sequence comprises an epitope that is recognized by a T cell that infiltrates a cervical neoplastic lesion or by a T cell from a draining lymph node. 
     
     
         8 . A peptide according to  claim 7 , wherein the epitope is selected from the group consisting of SEQ ID No.'s 5-26. 
     
     
         9 . A peptide according to  claim 8 , wherein the epitope is a HLA class I CTL epitope selected from the group consisting of SEQ ID No.'s 7, 14, 22-26. 
     
     
         10 . A peptide according to  claim 7 , wherein the contiguous amino acid sequence comprises an epitope that is presented by an HLA-B molecule. 
     
     
         11 . A peptide according to  claim 10 , wherein the HLA-B molecule is an HLA-B7, HLA-B14, HLA-B27 or HLA-B57 molecule. 
     
     
         12 . A peptide according to  claim 11 , wherein the epitope is selected from the group consisting of SEQ ID No.'s 7, 22, 24, 25 and 26. 
     
     
         13 . A peptide according to  claim 9 , wherein the contiguous amino acid sequence comprises an epitope that is presented by an HLA-A molecule. 
     
     
         14 . A peptide according to  claim 13 , wherein the HLA-A molecule is an HLA-A2, or HLA*0201 molecule. 
     
     
         15 . A peptide according to  claim 14 , wherein the epitope is selected from the group consisting of SEQ ID No.'s 23 and 26. 
     
     
         16 . A peptide according to  claim 1 , wherein the medicament comprises at least two different peptides as defined in any one of  claims 1 - 8 . 
     
     
         17 . A peptide according to  claim 1 , wherein the medicament further comprises at least one adjuvant. 
     
     
         18 . A peptide according to  claim 17 , wherein the adjuvant acts via a Toll-like receptor. 
     
     
         19 . A peptide according to  claim 1 , wherein the medicament is for intravenous, subcutaneous, intramuscular mucosal, intradermal and/or intracutaneous administration. 
     
     
         20 . A method for the prevention and/or treatment of an HPV related disease, wherein the method comprises the administration of an effective amount a peptide as defined in any one of  claim 1  or  7  to a subject in need thereof. 
     
     
         21 . A composition comprising a peptide as defined in  claim 1  or  7  and a pharmaceutically acceptable carrier. 
     
     
         22 . A composition according to  claim 21 , further comprising at least one adjuvant, wherein the adjuvant preferably acts via a Toll-like receptor. 
     
     
         23 . A nucleic acid molecule encoding at least one peptide as defined in  claim 1  or  7 . 
     
     
         24 . A nucleic acid molecule encoding a T cell receptor recognizing an epitope selected from the group consisting of SEQ ID No.'s 5-26. 
     
     
         25 . An isolated T cell comprising the nucleic acid molecule of  claim 24 . 
     
     
         26 . An isolated T cell comprising a T cell receptor recognizing an epitope selected from the group consisting of SEQ ID No.'s 5-26.