Long chain antigen containing interepitope sequence that promotes antigen presentation to t cells

Abstract

A long-chain peptide antigen includes a plurality of epitopes. An interepitope sequence located between two of the plurality of epitopes contains four to ten consecutive tyrosines, threonines, alanines, histidines, glutamines, or asparagines. The killer T-cell recognition epitopes form complexes with MHC class I molecules and are recognized by CD8+ killer T-cells when the complexes are presented on the surfaces of antigen-presenting cells. The helper T-cell recognition epitopes form complexes with MHC class II molecules and are recognized by CD4+ helper T-cells when the complexes are presented on the surfaces of antigen-presenting cells. The peptide is cleaved within the first interepitope sequence upon uptake of the peptide into antigen-presenting cells. The long-chain peptide antigen may be administered to a patient together with a hydrophobized polysaccharide, such as cholesterol-modified pullulan, and/or an adjuvant, such as CpG oligo DNA.

9 . (canceled) 
     
     
         10 . A peptide comprising:
 a first killer or helper T-cell recognition epitope,   a second killer or helper T-cell recognition epitope and   a first interepitope sequence that is located between the first and second killer or helper T-cell recognition epitopes, the first interepitope sequence consisting of four to ten consecutive tyrosines, threonines, alanines, histidines, glutamines, or asparagines,   wherein:   the killer T-cell recognition epitopes form complexes with MHC class I molecules and are recognized by CD8+ killer T-cells when said complexes are presented on the surfaces of antigen-presenting cells,   the helper T-cell recognition epitopes form complexes with MHC class II molecules and are recognized by CD4+ helper T-cells when said complexes are presented on the surfaces of antigen-presenting cells, and   the peptide is cleaved within the first interepitope sequence upon uptake of the peptide into antigen-presenting cells.   
     
     
         11 . The peptide as claimed in  claim 10 , wherein the peptide also has:
 a third killer or helper T-cell recognition epitope and a second interepitope sequence that is located between the second and third killer or helper T-cell recognition epitopes, the second interepitope sequence consisting of four to ten consecutive tyrosines, threonines, alanines, histidines, glutamines, or asparagines.   
     
     
         12 . A pharmaceutical composition comprising the peptide as claimed in  claim 10  and a hydrophobized polysaccharide. 
     
     
         13 . The pharmaceutical composition as claimed in  claim 12 , wherein the hydrophobized polysaccharide is cholesterol-modified pullulan (CHP). 
     
     
         14 . The pharmaceutical composition as claimed in  claim 13 , wherein the first and second killer or helper T-cell recognition epitopes are derived from at least one shared cancer antigenic protein and the peptide elicits an anti-tumor response in an animal or human. 
     
     
         15 . The peptide as claimed in  claim 10 , wherein the antigen-presenting cells are dendritic cells and macrophages. 
     
     
         16 . The pharmaceutical composition as claimed in  claim 13 , wherein the first and second killer or helper T-cell recognition epitopes are derived from at least one neoantigen generated by a gene mutation. 
     
     
         17 . The pharmaceutical composition as claimed in  claim 16 , further comprising an adjuvant. 
     
     
         18 . The pharmaceutical composition as claimed in  claim 17 , wherein the adjuvant is CpG oligo DNA. 
     
     
         19 . A pharmaceutical composition, wherein the pharmaceutical composition comprises the peptide of  claim 10 , the first and second recognition sequences respectively comprise different amino acid sequences found in one or more tumor-associated antigens, and the peptide elicits an anti-tumor response in an animal or human. 
     
     
         20 . The pharmaceutical composition as claimed in  claim 19 , wherein the first and second killer T-cell recognition epitopes consist of 8-10 amino acids and the first and second helper T-cell recognition epitopes consist of 15-20 amino acids. 
     
     
         21 . The peptide as claimed in  claim 10 , wherein the first and second recognition epitopes are adjacent to the interepitope sequence. 
     
     
         22 . The peptide as claimed in  claim 21 , wherein the antigen-presenting cells are dendritic cells and macrophages. 
     
     
         23 . A pharmaceutical composition comprising the peptide as claimed in  claim 21  and a hydrophobized polysaccharide. 
     
     
         24 . The pharmaceutical composition as claimed in  claim 23 , wherein the hydrophobized polysaccharide is cholesterol-modified pullulan (CHP). 
     
     
         25 . The pharmaceutical composition as claimed in  claim 24 , further comprising an adjuvant. 
     
     
         26 . The pharmaceutical composition as claimed in  claim 25 , wherein the adjuvant is CpG oligo DNA. 
     
     
         27 . A pharmaceutical composition, wherein the pharmaceutical composition comprises the peptide of  claim 10 , the first and second recognition epitopes respectively comprise different amino acid sequences found in one or more antigens of an infection-causing pathogen, and the peptide elicits an immune response against the infection-causing pathogen in an animal or human. 
     
     
         28 . The peptide as claimed in  claim 21 , wherein the peptide is a synthetic peptide and not a full-length recombinant protein. 
     
     
         29 . A pharmaceutical composition, wherein the pharmaceutical composition comprises the peptide of  claim 21 , the first and second recognition epitopes respectively comprise different amino acids found in one or more tumor-associated antigens, and the peptide elicits an anti-tumor response in humans. 
     
     
         30 . A pharmaceutical composition, wherein the pharmaceutical composition comprises the peptide of  claim 21 , the first and second recognition epitopes respectively comprise different amino acid sequences found in more or more antigens of an infection-causing pathogen, and the peptide elicits an immune response against an infection-causing pathogen in an animal or human. 
     
     
         31 . The peptide as claimed in  claim 10 , wherein the peptide is a synthetic peptide and not a full-length recombinant protein. 
     
     
         32 . The peptide as claimed in  claim 10 , wherein the first interepitope sequence consists of four to ten consecutive tyrosines, alanines, glutamines, or asparagines. 
     
     
         33 . The peptide as claimed in  claim 11 , wherein the second interepitope sequence consists of four to ten consecutive tyrosines, alanines, glutamines, or asparagines. 
     
     
         34 . The peptide as claimed in  claim 12 , wherein the first interepitope sequence consists of four to ten consecutive tyrosines, alanines, glutamines, or asparagines.