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 .- 18 . (canceled) 
     
     
         19 . A pharmaceutical composition comprising a peptide having a length of no more than 45 amino acids and comprising at least 31 and no more than 35 contiguous amino acids from the amino acid sequence of an HPV protein, wherein the contiguous amino acid sequence comprises at least one of SEQ ID NOs: 7, 14, 22, 24, 25, or 26. 
     
     
         20 . The pharmaceutical composition according to  claim 19 , wherein the contiguous amino acid sequence comprises an epitope that is presented by an HLA-B molecule. 
     
     
         21 . The pharmaceutical composition according to  claim 19 , wherein the composition comprises at least two different peptides as defined in  claim 19 . 
     
     
         22 . The pharmaceutical composition according to  claim 19 , further comprising a pharmaceutically acceptable adjuvant. 
     
     
         23 . The pharmaceutical composition according to  claim 19 , wherein the composition is for intravenous, subcutaneous, intramuscular, mucosal, intradermal and/or intracutaneous administration. 
     
     
         24 . The pharmaceutical composition according to  claim 19  for the treatment or prevention of an HPV related disease. 
     
     
         25 . The pharmaceutical composition according to  claim 23 , wherein the HPV related disease is selected from the group consisting of: cervical intraepithelial neoplasia of the cervix (CIN), vulva (VIN), vagina (VaIN), anus (AIN), and penis (PIN) and cancer of the cervix, vulva, vagina, anus, penis and head & neck. 
     
     
         26 . The pharmaceutical composition according to  claim 22 , wherein the pharmaceutically acceptable adjuvant is synthetic or wherein the pharmaceutically acceptable adjuvant acts via a Toll-like receptor. 
     
     
         27 . The pharmaceutical composition according to  claim 22 , wherein the pharmaceutically acceptable adjuvant is selected from the group consisting of: Gram positive bacterial glycolipids, fimbriae, outer membrane proteins, heatshock proteins, mycobacterial lipoarabinomannans, dsRNA, poly(I:C), Gram negative glycolipids, viral coat or envelope proteins, taxol or derivatives thereof, hyaluronan containing oligosaccharides or fibronectins, bacterial flagellae or flagellin, mycobacterial lipoproteins, group B  Streptococcus  heat labile soluble factor (GBS-F),  Staphylococcus  modulins, and imidazoquinolines, or wherein the pharmaceutically acceptable adjuvant is selected from the group consisting of: dsRNA, poly(I:C), unmethylated CpG DNA, IC 31 , IMSAVAC, Montanide ISA-51 and Montanide ISA 720. 
     
     
         28 . The pharmaceutical composition according to  claim 22 , wherein the pharmaceutical composition is an immunogenic pharmaceutical composition. 
     
     
         29 . The pharmaceutical composition according to  claim 19 , wherein the pharmaceutically acceptable adjuvant is physically linked to the peptide. 
     
     
         30 . The pharmaceutical composition according to  claim 19 , further comprising at least one immune modulator. 
     
     
         31 . The pharmaceutical composition according to  claim 19 , further comprising at least one additional peptide having a length of no more than 100 amino acids and comprising 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 of the additional peptide 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. 
     
     
         32 . The pharmaceutical composition according to  claim 31 , wherein the epitope of the additional peptide is selected from the group consisting of SEQ ID NO: 5, 6, 8, 9, 10, 11, 12, 13, 15, 16, 17, 18, 19, 20, 21, and 23. 
     
     
         33 . The pharmaceutical composition according to  claim 19 , wherein the peptide comprises SEQ ID NO: 34. 
     
     
         34 . The pharmaceutical composition according to  claim 19 , wherein the peptide consists of SEQ ID NO: 34. 
     
     
         35 . The pharmaceutical composition according to  claim 19 , wherein the peptide comprises SEQ ID NO: 35. 
     
     
         36 . The pharmaceutical composition according to  claim 19 , wherein the peptide consists of SEQ ID NO: 35. 
     
     
         37 . The pharmaceutical composition according to  claim 20 , wherein the HLA-B molecule is an HLA-B7, HLA-B14, HLA-B27 or HLA-B57 molecule.