Novel peptides and combination of peptides for use in immunotherapy and methods for generating scaffolds for the use against pancreatic cancer and other cancers

• US 20190315833A1
• Filed: 05/28/2019
• Published: 10/17/2019
• Est. Priority Date: 06/19/2015
• Status: Active Grant

• Current Assignee: Immatics Biotechnologies GmbH (Immatics NV)
• Original Assignee: Immatics Biotechnologies GmbH (Immatics NV)
• Inventors: MAHR, Andrea, WEINSCHENK, Toni, SCHOOR, Oliver, FRITSCHE, Jens, SINGH, Harpreet
• Granted Patent: US 11,485,769 B2
• Time in Patent Office: Days
• CPC Class Codes: A61K 2039/5158 Antigen-pulsed cells, e.g. T-cells
• CPC Class Codes: A61K 2039/572 cytotoxic response
• CPC Class Codes: A61K 35/15 Cells of the myeloid line, e.g. granulocytes, basophils, eosinophils, neutrophils, leucocytes, monocytes, macrophages or mast cells; Myeloid precursor cells; Antigen-presenting cells, e.g. dendritic cells presenting a specific antigen A61K39/00; therapeutic combinations of antibodies, or fragments thereof, and blood-derived cells A61K39/00
• CPC Class Codes: A61K 39/0011 Cancer antigens
• CPC Class Codes: A61K 39/001111 Immunoglobulin superfamily
• CPC Class Codes: A61K 39/001154 Enzymes
• CPC Class Codes: A61K 39/001162 Kinases, e.g. Raf or Src
• CPC Class Codes: A61K 39/4611 T-cells, e.g. tumor infiltrating lymphocytes [TIL], lymphokine-activated killer cells [LAK] or regulatory T cells [Treg]
• CPC Class Codes: A61K 39/4644 Cancer antigens
• CPC Class Codes: A61K 51/1027 against receptors, cell-surface antigens or cell-surface determinants
• CPC Class Codes: A61K 51/1057 the tumor cell being from liver or pancreas
• CPC Class Codes: A61P 35/00 Antineoplastic agents
• CPC Class Codes: C07K 14/4748 Tumour specific antigens; Tumour rejection antigen precursors [TRAP], e.g. MAGE
• CPC Class Codes: C07K 14/70503 Immunoglobulin superfamily
• CPC Class Codes: C07K 14/70539 MHC-molecules, e.g. HLA-molecules
• CPC Class Codes: C07K 16/2833 against MHC-molecules, e.g. HLA-molecules
• CPC Class Codes: C07K 16/303 Liver or Pancreas
• CPC Class Codes: C07K 2317/72 Increased effector function due to an Fc-modification
• CPC Class Codes: C07K 2317/73 Inducing cell death, e.g. apoptosis, necrosis or inhibition of cell proliferation
• CPC Class Codes: C07K 2319/00 Fusion polypeptide
• CPC Class Codes: C07K 2319/30 : Non-immunoglobulin-derived peptide or protein having an immunoglobulin constant or Fc region, or a fragment thereof, attached thereto
• CPC Class Codes: C07K 2319/55 : containing a fusion with a toxin, e.g. diphteria toxin
• CPC Class Codes: C12N 15/115 : Aptamers, i.e. nucleic acids binding a target molecule specifically and with high affinity without hybridising therewith ; Nucleic acids binding to non-nucleic acids, e.g. aptamers
• CPC Class Codes: C12N 2310/16 : Aptamers
• CPC Class Codes: C12N 5/0636 : T lymphocytes
• CPC Class Codes: C12P 21/02 : having a known sequence of two or more amino acids, e.g. glutathione
• CPC Class Codes: C12Q 1/6881 : for tissue or cell typing, e.g. human leukocyte antigen [HLA] probes
• CPC Class Codes: C12Q 2600/156 : Polymorphic or mutational markers
• CPC Class Codes: C12Q 2600/158 : Expression markers
• CPC Class Codes: G01N 2333/70539 : MHC-molecules, e.g. HLA-molecules
• CPC Class Codes: G01N 33/56977 : HLA or MHC typing

Abstract

The present invention relates to peptides, proteins, nucleic acids and cells for use in immunotherapeutic methods. In particular, the present invention relates to the immunotherapy of cancer. The present invention furthermore relates to tumor-associated T-cell peptide epitopes, alone or in combination with other tumor-associated peptides that can for example serve as active pharmaceutical ingredients of vaccine compositions that stimulate anti-tumor immune responses, or to stimulate T cells ex vivo and transfer into patients. Peptides bound to molecules of the major histocompatibility complex (MHC), or peptides as such, can also be targets of antibodies, soluble T-cell receptors, and other binding molecules.

Claims

1. An expression vector expressing a nucleic acid encoding a peptide consisting of the amino acid sequence selected from SEQ ID NOs:

45, 46, 6, 1-5, 7-29, 31-44, 47-80, 82-98, and 100-161.

2. A recombinant host cell comprising the expression vector of claim 1, wherein said host cell is a dendritic cell or a macrophage.

3. A method for producing a peptide consisting of the amino acid sequence selected from SEQ ID NOs:

45, 46, 6, 1-5, 7-29, 31-44, 47-80, 82-98, and 100-161, comprising culturing the host cell of claim 2, and isolating the peptide from the host cell or its culture medium.

4. An in vitro method for producing activated antigen-specific CD8+ cytotoxic T lymphocytes, comprising contacting in vitro T cells with antigen loaded human HLA-A*02 expressed on the surface of a suitable antigen-presenting cell or an artificial construct mimicking an antigen-presenting cell for a period of time sufficient to activate said T cells, wherein said antigen is a peptide consisting of the amino acid sequence selected from SEQ ID NOs:

45, 46, 6, 1-5, 7-29, 31-44, 47-80, 82-98, and 100-161.

5. The method of claim 4, wherein the T cells are autologous to the patient.

6. The method of claim 4, wherein the T cells are obtained from a healthy donor.

7. The method of claim 4, wherein the T cells are obtained from tumor infiltrating lymphocytes or peripheral blood mononuclear cells.

8. The method of claim 4, wherein the activated T cells are expanded in vitro.

9. The method of claim 4, wherein the antigen presenting cell is infected with recombinant virus expressing the peptide.

10. The method of claim 9, wherein the antigen presenting cell is a dendritic cell or a macrophage.

11. The method of claim 8, wherein the expansion is in the presence of an anti-CD28 antibody and IL-12.

12. A pharmaceutical composition comprising a peptide consisting of the amino acid sequence selected from SEQ ID NOs:

45, 46, 6, 1-5, 7-29, 31-44, 47-80, 82-98, and 100-161 in the form of a pharmaceutically acceptable salt and an immune-stimulating adjuvant.

13. The pharmaceutical composition of claim 12, wherein the pharmaceutically acceptable salt is chloride salt.

14. The pharmaceutical composition of claim 12, wherein the pharmaceutically acceptable salt is acetate salt.

15. The pharmaceutical composition of claim 12, wherein the adjuvant is selected from anti-CD40 antibody, imiquimod, resiquimod, GM-CSF, cyclophosphamide, 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.

16. The pharmaceutical composition of claim 12, wherein the adjuvant comprises IL-2.

17. The pharmaceutical composition of claim 12, wherein the adjuvant comprises IL-7.

18. The pharmaceutical composition of claim 12, wherein the adjuvant comprises IL-15.

19. The pharmaceutical composition of claim 12, wherein the adjuvant comprises IL-21.

20. The pharmaceutical composition of claim 12, wherein the adjuvant comprises cyclophosphamide.