Use of HLA-A*11:01-restricted hepatitis B virus (HBV) peptides for identifying HBV-specific CD8+ T cells

Patent metadata

Field	Value
Publication number	US-12414990-B2
Application number	US-202017421816-A
Country	US
Kind code	B2
Filing date	Jan 13, 2020
Priority date	Jan 11, 2019
Publication date	Sep 16, 2025
Grant date	Sep 16, 2025

Abstract

The present invention relates to peptides and their ability to identify and bind to T cells specific for HBV-infected hepatocytes. In a first aspect of the invention, there is provided a peptide comprising an amino acid sequence selected from the group consisting of STLPETAVVRR (SEQ ID NO: 21), STLPETAVVR (SEQ ID NO: 22), STLPETTVVRR (SEQ ID NO: 23), STLPETTVTRR (SEQ ID NO: 24), STPPETTVVRR (SEQ ID NO: 25), STLPETTVVGR (SEQ ID NO: 26) and STIPETTVVRR (SEQ ID NO: 27), wherein the peptide is derived from Hepatitis B virus core169 and is capable of binding HLA-A*1101 and when bound to HLA-A*1101 is capable of identifying T cells specific for Hepatitis B virus. In a second aspect of the invention, there is provided a T cell expressing a T cell receptor (TCR) molecule, wherein the TCR molecule comprises an amino acid sequence selected from the group consisting of CASGDSNSPLHF (SEQ ID NO: 17), CASSGGQIVYEQYF (SEQ ID NO: 18), CSARGGRGGDYTF (SEQ ID NO: 19) and CASSQDWTEAFF (SEQ ID NO: 20), and wherein the TCR molecule is able to bind to a peptide according to the first aspect of the invention.

First claim

The invention claimed is:

1. A method for identifying Hepatitis B virus antigen-specific T cells, the method comprising contacting a population of T cells with a peptide comprising an amino acid sequence selected from the group consisting of STLPETAVVRR (SEQ ID NO: 21), STLPETAVVR (SEQ ID NO: 22), STLPETTVTRR (SEQ ID NO: 24), STPPETTVVRR (SEQ ID NO: 25), STLPETTVVGR (SEQ ID NO: 26) and STIPETTVVRR (SEQ ID NO: 27), wherein the peptide is less than 30 amino acids long and is capable of binding HLA-A* 1101 and when bound to HLA-A* 1101 is capable of identifying T cells specific for Hepatitis B virus.

2. A T cell receptor (TCR) molecule comprising a TCR beta chain complementarity determining region 3 (CDR3) comprising an amino acid sequence selected from the group consisting of: CASGDSNSPLHF (SEQ ID NO: 17), CASSGGQIVYEQYF (SEQ ID NO: 18), CSARGGRGGDYTF (SEQ ID NO: 19) and CASSQDWTEAFF (SEQ ID NO: 20), wherein the TCR molecule is able to bind to a peptide, wherein the peptide comprises an amino acid sequence selected from the group consisting of STLPETAVVRR (SEQ ID NO: 21), STLPETAVVR (SEQ ID NO: 22), STLPETTVIRR (SEQ ID NO: 24), STPPETTVVRR (SEQ ID NO: 25), STLPETTVVGR (SEQ ID NO: 26) and STIPETTVVRR (SEQ ID NO: 27).

3. A polynucleotide encoding the TCR molecule according to claim 2 .

4. The polynucleotide according to claim 3 , comprising a sequence selected from the group consisting of SEQ ID NOs: 1 to 16.

5. An expression vector comprising the polynucleotide according to claim 3 .

6. An isolated host cell comprising the polynucleotide according to claim 3 .

7. The isolated host cell according to claim 6 , wherein the host cell is a T cell derived from a patient.

8. An isolated T cell modified to express the TCR molecule according to claim 2 .

9. A pharmaceutical composition comprising a peptide and a pharmaceutically acceptable carrier, wherein the peptide comprises an amino acid sequence selected from the group consisting of STLPETAVVRR (SEQ ID NO: 21), STLPETAVVR (SEQ ID NO: 22), STLPETTVTRR (SEQ ID NO: 24), STPPETTVVRR (SEQ ID NO: 25), STLPETTVVGR (SEQ ID NO: 26) and STIPETTVVRR (SEQ ID NO: 27), wherein the peptide is less than 30 amino acids long and is capable of binding HLA-A*1101.

10. A method of treating a Hepatitis B virus infection in an individual, the method comprising administering to the individual an effective amount of a peptide, wherein the peptide comprises an amino acid sequence selected from the group consisting of STLPETAVVRR (SEQ ID NO: 21), STLPETAVVR (SEQ ID NO: 22), STLPETTVIRR (SEQ ID NO: 24), STPPETTVVRR (SEQ ID NO: 25), STLPETTVVGR (SEQ ID NO: 26) and STIPETTVVRR (SEQ ID NO: 27), wherein the peptide is less than 30 amino acids long and is capable of binding HLA-A*1101.

11. A method of combating a Hepatitis B virus infection in a patient which carries HLA-A*1101, the method comprising:
(a) obtaining T cells from the patient;
(b) introducing into the T cells a polynucleotide encoding the TCR molecule according to claim 2 ; and
(c) introducing the T cells produced in step (b) into the patient.

12. The method according to claim 11 , wherein the polynucleotide is transfected into or introduced to the T cells by electroporation.

13. An isolated host cell comprising the expression vector according to claim 5 .

14. A pharmaceutical composition comprising the isolated host cell according to claim 7 and a pharmaceutically acceptable carrier.

15. A vaccine against Hepatitis B virus infection comprising the isolated T cell according to claim 8 .

16. A method of treating a Hepatitis B virus infection in an individual, the method comprising administering to the individual an effective amount of the isolated T cell according to claim 8 .

Assignees

• Agency Science Tech & Res

Inventors

• Cheng Yang
• Newell Evan

Classifications

• A61K40/46

  Viral antigens · CPC title

• A61K40/32

  T-cell receptors [TCR] · CPC title

• A61K40/11

  T-cells, e.g. tumour infiltrating lymphocytes [TIL] or regulatory T [Treg] cells; Lymphokine-activated killer [LAK] cells · CPC title

• C12N15/86

  Viral vectors · CPC title

• A61K35/17

  Lymphocytes; B-cells; T-cells; Natural killer cells; Interferon-activated or cytokine-activated lymphocytes (when activated by a specific antigen A61K39/00) · CPC title