Novel Promiscuous HPV16-Derived T Helper Epitopes for Immunotherapy

Abstract

The present invention relates to novel amino acid sequences of peptides derived from HPV 16 that are able to bind to MHC complexes of class II, and elicit an immune response. The present invention further relates to pharmaceutical products, such as vaccines and T-cells, based on said epitopes.

1 . A peptide comprising a sequence according to SEQ ID NO: 4 or a variant thereof that is at least 80% homologous to SEQ ID NO: 4, wherein said peptide, or one or more parts thereof, has the ability to bind to a molecule of the human major histocompatibility complex (MHC) class-II or -I, and wherein said peptide has a length of 15 to 50 amino acids. 
     
     
         2 . The peptide according to  claim 1 , wherein said peptide or variant has from 15 to 30 amino acids. 
     
     
         3 . The peptide according to  claim 1 , wherein said peptide consists of the amino acid sequence according to SEQ ID NO: 4. 
     
     
         4 . The peptide according to  claim 1 , wherein said peptide has an IC 50 ≤60 nM. 
     
     
         5 . A pharmaceutical composition comprising the peptide according to  claim 1 , and optionally at least one additional peptide consisting of an amino acid sequence selected from the group of SEQ ID NOs: 26, 9, 7, and 18. 
     
     
         6 . The peptide according to  claim 1 , wherein said peptide is part of a fusion protein or other fusion molecule. 
     
     
         7 . A nucleic acid encoding the peptide according to  claim 1 . 
     
     
         8 . An expression vector capable of expressing the nucleic acid according to  claim 7 . 
     
     
         9 . A host cell comprising a nucleic acid encoding the peptide of  claim 1 , wherein said host cell is an antigen presenting cell and presents the peptide according to  claim 1 . 
     
     
         10 . A method for producing the peptide according to  claim 1 , said method comprising synthesizing said peptide, or culturing a host cell comprising a nucleic acid encoding the peptide of  claim 1 , wherein said host cell is an antigen presenting cell and presents the peptide according to  claim 1 , and isolating said peptide from said host cell or a culture medium thereof. 
     
     
         11 . A method for producing activated T cells, the method comprising contacting T H  cells with antigen loaded human class I or II MHC molecules expressed on the surface of suitable antigen-presenting cells for a period of time sufficient to activate said T cells in an antigen specific manner, wherein said antigen is a peptide according to  claim 1 . 
     
     
         12 . An activated T cell, produced by the method according to  claim 11 , wherein said T cell selectively recognizes cells that express an HPV polypeptide comprising a sequence according to SEQ ID NO: 4 or a variant thereof that is at least 80% homologous to SEQ ID NO: 4, wherein said peptide, or one or more parts thereof, have the ability to bind to a molecule of the human major histocompatibility complex (MHC) class-II or -I, and wherein said peptide has a length of from 15 to 50 amino acids. 
     
     
         13 . A pharmaceutical preparation, comprising at least one of: a nucleic acid encoding the peptide according to  claim 1 ; a host cell comprising a nucleic acid encoding the peptide of  claim 1 , wherein said host cell is an antigen presenting cell and presents the peptide according to  claim 1 ; an activated T cell, wherein said T cell selectively recognizes cells that express an HPV polypeptide comprising a sequence according to SEQ ID NO: 4 or a variant thereof that is at least 80% homologous to SEQ ID NO: 4, wherein said peptide, or one or more parts thereof, has the ability to bind to a molecule of the human major histocompatibility complex (MHC) class-II or -I, and wherein said peptide has from 15 to 50 amino acids; and wherein said preparation further comprises a pharmaceutically acceptable excipient. 
     
     
         14 . A method for treating HPV infection, HPV-related premalignancies and/or malignancies comprising administering the pharmaceutical preparation according to  claim 13  to a patient in need of said treatment. 
     
     
         15 . The method for treating HPV infection, HPV-related premalignancies and/or malignancies according to  claim 14 , wherein said treatment is MHC-I and/or MHC-II peptide presentation dependent. 
     
     
         16 . The peptide according to  claim 1 , wherein said peptide or variant has from 15 to 20 amino acids.