Novel peptides and combination of peptides for use in immunotherapy against cll and other cancers

Patent metadata

Field	Value
Publication number	US-2017173131-A1
Application number	US-201615374480-A
Country	US
Kind code	A1
Filing date	Dec 9, 2016
Priority date	Dec 10, 2015
Publication date	Jun 22, 2017
Grant date	—

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.

First claim

1 . A peptide comprising an amino acid sequence comprising SEQ ID No. 153, and/or a variant sequence thereof which is at least 88% homologous to SEQ ID No. 153, wherein said variant binds to molecule(s) of the major histocompatibility complex (MHC) and/or induces T cells cross-reacting with said variant peptide; and a pharmaceutical acceptable salt thereof, wherein said peptide is not a full-length polypeptide.

2 . The peptide or variant according to claim 1 , wherein said peptide has the ability to bind to a MHC class-I or -II molecule, and wherein said peptide, when bound to said MHC, is capable of being recognized by CD4 and/or CD8 T cells.

3 . The peptide or variant thereof according to claim 1 , wherein the amino acid sequence thereof comprises a continuous stretch of amino acids according to the group of SEQ ID No. 153.

4 . The peptide or variant thereof according to claim 1 , wherein said peptide or variant thereof has an overall length of from 8 to 100, optionally from 8 to 30, and optionally from 8 to 16 amino acids, and optionally wherein the peptide consists or consists essentially of an amino acid of SEQ ID No. 153.

5 . The peptide or variant thereof according to claim 1 , wherein said peptide is part of a fusion protein, optionally comprising N-terminal amino acids of the HLA-DR antigen-associated invariant chain (Ii).

6 . A nucleic acid, encoding a peptide or variant thereof according to claim 1 , optionally linked to a heterologous promoter sequence.

7 . An expression vector capable of expressing the nucleic acid according to claim 6 .

8 . The peptide or variant thereof according to claim 1 , a nucleic acid encoding said peptide or variant or an expression vector capable of expressing said nucleic acid, or a host cell comprising said peptide or variant, capable of being used in medicine.

9 . A method for producing the peptide or variant thereof according to claim 1 , the method comprising culturing a host cell that presents the peptide or variant, or expresses a nucleic acid encoding said peptide or variant or comprises an expression vector capable of expressing said nucleic acid, and isolating the peptide or variant thereof from the host cell or its culture medium.

10 . An in vitro method for producing activated T lymphocytes, the method comprising contacting in vitro T cells with antigen loaded human class I or II MHC molecules 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 in an antigen specific manner, wherein said antigen is a peptide according to claim 1 .

11 . An activated T cell, optionally an activated T lymphocyte, produced by the method according to claim 10 , that selectively recognizes a cell which presents a polypeptide comprising an amino acid sequence of SEQ ID No. 153, and variant sequences thereof which are at least 88% homologous to SEQ ID No. 153.

12 . A method for killing target cells in a patient which target cells present a polypeptide comprising an amino acid sequence of SEQ ID No. 153, and variant sequences thereof which are at least 88% homologous to SEQ ID No. 153, the method comprising administering to the patient an effective number of activated T cells as defined in claim 11 .

13 . An antibody, optionally a soluble or membrane-bound antibody, that specifically recognizes the peptide or variant thereof according to claim 1 , optionally the peptide or variant are bound to an MHC molecule, and wherein said antibody optionally carries a further effector function, optionally an immune stimulating domain or toxin, wherein said antibody is optionally a polyclonal antibody, monoclonal antibody, bi-specific antibody and/or a chimeric antibody.

14 . A method for the treatment of cancer and/or or in the manufacture of a medicament against cancer, or in a diagnostic method for detection of cancerous cells, said method comprising utilizing a peptide or variant according to claim 1 , a nucleic acid encoding said peptide or variant or an expression vector capable of expressing said nucleic acid, or a host cell comprising said peptide or variant, an activated T lymphocyte that selectively recognizes a cell which presents said peptide or variant or the antibody optionally a soluble or membrane-bound antibody, that specifically recognizes the peptide or variant.

15 . The method of claim 14 , wherein said cancer is selected from the group consisting of ovarian cancer, non-small cell lung cancer, small cell lung cancer, kidney cancer, brain cancer, colon or rectum cancer, stomach cancer, liver cancer, pancreatic cancer, prostate cancer, leukemia, breast cancer, Merkel cell carcinoma, melanoma, esophageal cancer, urinary bladder cancer, uterine cancer, gallbladder cancer, bile duct cancer and other tumors that show an overexpression of a protein from which a peptide SEQ ID No. 153 is derived from.

16 . A kit comprising:
(a) a container comprising a pharmaceutical composition containing the peptide(s) or the variant according to claim 1 , a nucleic acid encoding said peptide or variant or an expression vector capable of expressing said nucleic acid, or a host cell comprising said peptide or variant, an activated T lymphocyte that selectively recognizes a cell which presents said peptide or variant or the antibody optionally a soluble or membrane-bound antibody, that specifically recognizes the peptide or variant, in solution or in lyophilized form; (b) optionally, a second container containing a diluent or reconstituting solution for the lyophilized formulation; (c) optionally, at least one more peptide of SEQ ID No. 153 or variant, and (d) optionally, instructions for (i) use of the solution or (ii) reconstitution and/or use of the lyophilized formulation.

17 . A T-cell receptor, optionally soluble or membrane-bound, that is reactive with an HLA ligand, wherein said ligand has at least 88% identity to an amino acid sequence of SEQ ID No. 153.

18 . A pharmaceutical composition comprising at least one active ingredient selected from the group consisting of
a) a peptide of SEQ ID No. 153 or variant thereof; b) a T-cell receptor reactive with a peptide and/or the peptide-MHC complex according to a); c) a fusion protein comprising a peptide according to a), and the N-terminal amino acids 1 to 80 of the HLA-DR antigen-associated invariant chain (Ii); d) a nucleic acid encoding for any of a) to c) or an expression vector comprising said nucleic acid, e) a host cell comprising the expression vector of d, f) an activated T-lymphocyte, obtained by a method comprising contacting in vitro T cells with a peptide according to a) expressed on the surface of a suitable antigen presenting cell for a period of time sufficient to activate said T cell in an antigen specific manner, as well as a method to transfer these activated T cells into the autologous or other patients; g) an antibody, or soluble T-cell receptor, reactive to a peptide and/or the peptide-MHC complex according to a) and/or a cell presenting a peptide according to a), and potentially modified by fusion with for example immune-activating domains or toxins, h) an aptamer recognizing a peptide of SEQ ID 153, and/or a complex of a peptide of SEQ ID No. 153 with a MHC molecule, i) a conjugated or labelled peptide or scaffold according to any of a) to h) and a pharmaceutically acceptable carrier, and optionally, pharmaceutically acceptable excipients and/or stabilizers.

19 . An aptamer that specifically recognizes th

Assignees

• Immatics Biotechnologies Gmbh

Inventors

• Mahr Andrea
• Weinschenk Toni
• Wiebe Anita
• Schoor Oliver
• Fritsche Jens
• Singh Harpreet

Classifications

• A61P7/00

  Drugs for disorders of the blood or the extracellular fluid · CPC title

• A61P35/00

  Antineoplastic agents · CPC title

• A61P35/02

  specific for leukemia · CPC title

• A61P1/00

  Drugs for disorders of the alimentary tract or the digestive system · CPC title

• A61P15/00

  Drugs for genital or sexual disorders (for disorders of sex hormones A61P5/24); Contraceptives · CPC title