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

• US 10,618,948 B2
• Filed: 05/21/2018
• Issued: 04/14/2020
• 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
• Primary Examiner(s): Canella, Karen A.
• Application Number:
  US15/984,681
• Publication Number:
  US 20180251519A1
• Time in Patent Office: 694 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 39/0011 Cancer antigens
• 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. A method for producing activated antigen-specific CD8+ cytotoxic T cells that selectively recognize cancer cells that aberrantly present a peptide consisting of the amino acid sequence of VVYDDSTGLIRL (SEQ ID NO:

81) in a complex with an HLA-A*02 comprising;

isolating CD8⁺ T cells from a HLA-A*02 donor;

contacting the isolated CD8⁺ T cells with antigen-presenting cells that display an antigen in a complex with HLA-A*02 for a period of time sufficient to activate the CD8⁺T cells, wherein said antigen is a peptide consisting of the amino acid sequence of VVYDDSTGLIRL (SEQ ID NO;

81).

2. The method of claim 1, wherein the HLA-A*02 donor is a patient with cancer.

3. The method of claim 2, wherein the cancer is lung cancer, CNS tumor, neuroblastoma, prostate cancer, lymphocytic leukemia, Merkel Cell carcinoma (MCC), ovarian cancer or oral cancer.

4. The method of claim 2, wherein the cancer is lung cancer.

5. The method of claim 1, wherein the CD8⁺ T cells are obtained from tumor infiltrating lymphocytes or peripheral blood mononuclear cells.

6. The method of claim 1, wherein the HLA-A*02 donor is a healthy donor.

7. The method of claim 1, wherein the antigen presenting cells are dendritic cells or macrophages.

8. The method of claim 1, wherein the antigen presenting cells are infected with a recombinant virus expressing the peptide.

9. The method of claim 1, wherein the antigen presenting cells are artificial antigen presenting cells (aAPC).

10. The method of claim 1, further comprising expanding the activated T cells in vitro.

11. The method of claim 10, wherein the expansion is in the presence of an anti-CD28 antibody and IL-12.