Method of eliciting a CD8+ cytotoxic response in hepatocellular carcinoma patients with a population of activated T cells

Patent metadata

Field	Value
Publication number	US-11672848-B2
Application number	US-202217852623-A
Country	US
Kind code	B2
Filing date	Jun 29, 2022
Priority date	Dec 23, 2014
Publication date	Jun 13, 2023
Grant date	Jun 13, 2023

Abstract

A method of eliciting an immune response in a patient who has a cancer includes administering to said patient a composition containing a population of activated T cells that selectively recognize the cancer cells in the patient that aberrantly express a peptide consisting of the amino acid sequence of ALVEQGFTV (SEQ ID NO: 5), in which the peptide is in a complex with an MHC molecule.

First claim

The invention claimed is:

1. A method of eliciting a CD8+ cytotoxic T cell response in an HLA-A*02+ patient who has hepatocellular carcinoma (HCC) that presents at the cell surface a peptide consisting of the amino acid sequence of ALVEQGFTV (SEQ ID NO: 5), comprising
administering to said identified patient a composition comprising a population of activated antigen-specific CD8+ cytotoxic T cells to kill the HCC cells in the identified patient,
wherein the population of activated antigen-specific CD8+ cytotoxic T cells recognize the HCC cells by interacting through their TCR with a peptide consisting of the amino acid sequence of ALVEQGFTV (SEQ ID NO: 5) in a complex with HLA-A*02 presented at the surface of the HCC cells,
wherein the activated antigen-specific CD8+ cytotoxic T cells are autologous to the patient.

2. The method of claim 1 , wherein the activated antigen-specific CD8+ cytotoxic T cells are obtained from tumor infiltrating lymphocytes or peripheral blood mononuclear cells.

3. The method of claim 1 , wherein the composition further comprises an adjuvant.

4. The method of claim 3 , wherein the adjuvant is selected from the group consisting of anti-CD40 antibody, imiquimod, resiquimod, GM-CSF, cyclophosphamide, Sunitinib, bevacizumab, interferon-alpha, interferon-beta, CpG oligonucleotides and derivatives, poly-(I:C) and derivatives, RNA, sildenafil, particulate formulations with poly(lactide co-glycolide) (PLG), virosomes, interleukin (IL)-1, IL-2, IL-4, IL-7, IL-12, IL-13, IL-15, IL-21, and IL-23.

5. The method of claim 4 , wherein the adjuvant is IL-2.

6. The method of claim 4 , wherein the adjuvant is IL-7.

7. The method of claim 4 , wherein the adjuvant is IL-15.

8. The method of claim 4 , wherein the adjuvant is IL-21.

9. The method of claim 4 , wherein the adjuvant is IL-12.

10. A method of eliciting a CD8+ cytotoxic T cell response in an HLA-A*02+ patient who has hepatocellular carcinoma (HCC), wherein the HCC cells overexpress an APOB polypeptide comprising the amino acid sequence of ALVEQGFTV (SEQ ID NO: 5) as compared to a panel of normal tissues, wherein the HCC cells present at the cell surface a peptide consisting of the amino acid sequence of ALVEQGFTV (SEQ ID NO: 5) in a complex with HLA-A*02, comprising
administering to said patient who has HCC a composition comprising a population of activated antigen-specific CD8+ cytotoxic T cells to kill the HCC cells in the patient,
wherein the population of the activated antigen-specific CD8+ cytotoxic T cells recognize the HCC cells by interacting through their TCR with a peptide consisting of the amino acid sequence of ALVEQGFTV (SEQ ID NO: 5) in a complex with HLA-A*02 presented at the surface of the HCC cells,
wherein the activated antigen-specific CD8+ cytotoxic T cells are autologous to the patient.

11. The method of claim 10 , further comprising expanding the activated T cells in vitro.

12. The method of claim 11 , wherein the expanding is in the presence of an anti-CD28 antibody and IL-12.

13. The method of claim 10 , wherein the composition further comprises an adjuvant.

14. The method of claim 13 , wherein the adjuvant is selected from the group consisting of anti-CD40 antibody, imiquimod, resiquimod, GM-CSF, cyclophosphamide, Sunitinib, bevacizumab, interferon-alpha, interferon-beta, CpG oligonucleotides and derivatives, poly-(I:C) and derivatives, RNA, sildenafil, particulate formulations with poly(lactide co-glycolide) (PLG), virosomes, interleukin (IL)-1, IL-2, IL-4, IL-7, IL-12, IL-13, IL-15, IL-21, and IL-23.

15. The method of claim 14 , wherein the adjuvant is IL-7.

16. The method of claim 14 , wherein the adjuvant is IL-15.

17. The method of claim 14 , wherein the adjuvant is IL-21.

18. The method of claim 14 , wherein the adjuvant is IL-2.

19. The method of claim 10 , wherein the antigen presenting cell is a dendritic cell or a macrophage.

20. The method of claim 10 , wherein the activated antigen-specific CD8+ cytotoxic T cells are produced by contacting the CD8+ cytotoxic T cells with an antigen presenting cell that present at the cell surface a peptide consisting of ALVEQGFTV (SEQ ID NO: 5) in a complex with HLA-A*02 in vitro, thereby activating the CD8+ cytotoxic T cells.

Assignees

• Immatics Biotechnologies Gmbh

Inventors

• Weinschenk Toni
• Mahr Andrea
• Fritsche Jens
• Mueller Phillip
• Wiebe Anita
• Kutscher Sarah

Classifications

• A61P35/00

  Antineoplastic agents · CPC title

• C07K2319/40

  containing a tag for immunodetection, or an epitope for immunisation · CPC title

• A61P1/16

  for liver or gallbladder disorders, e.g. hepatoprotective agents, cholagogues, litholytics · CPC title

• C07K7/00

  Peptides having 5 to 20 amino acids in a fully defined sequence; Derivatives thereof · CPC title

• C12N2310/16

  Aptamers · CPC title