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

Patent metadata

Field	Value
Publication number	US-11179450-B2
Application number	US-201816035922-A
Country	US
Kind code	B2
Filing date	Jul 16, 2018
Priority date	Oct 1, 2013
Publication date	Nov 23, 2021
Grant date	Nov 23, 2021

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. 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

The invention claimed is:

1. 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,
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,
wherein 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
wherein the first interepitope sequence mediates enhanced uptake of the peptide into antigen-presenting cells.

2. The peptide as claimed in claim 1 , 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.

3. A pharmaceutical composition comprising the peptide as claimed in claim 1 and a hydrophobized polysaccharide.

4. The pharmaceutical composition as claimed in claim 3 , wherein the hydrophobized polysaccharide is cholesterol-modified pullulan (CHP).

5. The pharmaceutical composition as claimed in claim 4 , 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 a human.

6. The peptide as claimed in claim 1 , wherein the antigen-presenting cells are dendritic cells and macrophages.

7. The pharmaceutical composition as claimed in claim 4 , wherein the first and second killer or helper T-cell recognition epitopes are derived from at least one neoantigen generated by a gene mutation.

8. The pharmaceutical composition as claimed in claim 6 , further comprising an adjuvant.

9. The pharmaceutical composition as claimed in claim 8 , wherein the adjuvant is CpG oligo DNA.

10. A pharmaceutical composition, wherein the pharmaceutical composition comprises the peptide of claim 1 , the first and second recognition epitopes 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 a human.

11. The pharmaceutical composition as claimed in claim 10 , 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.

12. The peptide as claimed in claim 1 , wherein the first and second recognition epitopes are adjacent to the interepitope sequence.

13. The peptide as claimed in claim 12 , wherein the antigen-presenting cells are dendritic cells and macrophages.

14. A pharmaceutical composition comprising the peptide as claimed in claim 12 and a hydrophobized polysaccharide.

15. The pharmaceutical composition as claimed in claim 14 , wherein the hydrophobized polysaccharide is cholesterol-modified pullulan (CHP).

16. The pharmaceutical composition as claimed in claim 15 , further comprising an adjuvant.

17. The pharmaceutical composition as claimed in claim 16 , wherein the adjuvant is CpG oligo DNA.

18. A pharmaceutical composition, wherein the pharmaceutical composition comprises the peptide of claim 1 , 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 a human.

19. The peptide as claimed in claim 12 , wherein the first interepitope sequence consists of six to ten consecutive tyrosines.

20. A pharmaceutical composition, wherein the pharmaceutical composition comprises the peptide of claim 12 , the first and second recognition epitopes respectively comprise different amino acid sequences found in one or more tumor-associated antigens, and the peptide elicits an anti-tumor response in humans.

21. A pharmaceutical composition, wherein the pharmaceutical composition comprises the peptide of claim 12 , 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.

22. The peptide as claimed in claim 1 , wherein the peptide is a synthetic peptide and not a full-length recombinant protein.

23. The peptide as claimed in claim 12 , wherein the peptide is a synthetic peptide and not a full-length recombinant protein.

Assignees

• Univ Mie
• Univ Kyoto

Inventors

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

Classifications

• A61K39/0011 Primary

  Cancer antigens · CPC title

• A61K39/015

  Hemosporidia antigens, e.g. Plasmodium antigens · CPC title

• A61P31/04

  Antibacterial agents · CPC title

• A61K39/12

  Viral antigens · CPC title

• C12N2710/16134

  Use of virus or viral component as vaccine, e.g. live-attenuated or inactivated virus, VLP, viral protein · CPC title