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

Patent metadata

Field	Value
Publication number	US-2022062398-A1
Application number	US-202117529475-A
Country	US
Kind code	A1
Filing date	Nov 18, 2021
Priority date	Oct 1, 2013
Publication date	Mar 3, 2022
Grant date	—

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.

First claim

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.

Assignees

• Univ Mie
• Univ Kyoto

Inventors

• Shiku Hiroshi
• Harada Naozumi
• Muraoka Daisuke
• Akiyoshi Kazunari

Classifications

• A61K39/0011 Primary

  Cancer antigens · CPC title

• A61P31/04

  Antibacterial agents · CPC title

• A61P35/00

  Antineoplastic agents · CPC title

• A61K2039/6087

  Polysaccharides; Lipopolysaccharides [LPS] · CPC title

• C12N2710/16122

  New viral proteins or individual genes, new structural or functional aspects of known viral proteins or genes · CPC title