Novel peptides and combination of peptides and scaffolds for use in immunotherapy against Renal Cell Carcinoma (RCC) and other cancers

Patent metadata

Field	Value
Publication number	US-2016289296-A1
Application number	US-201615082920-A
Country	US
Kind code	A1
Filing date	Mar 28, 2016
Priority date	Mar 31, 2015
Publication date	Oct 6, 2016
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 SEQ ID No. 38, and variant sequences thereof which are at least 88% homologous to SEQ ID No. 38; and a pharmaceutical acceptable salt thereof, wherein said peptide is not a full-length polypeptide.

2 . The peptide according to claim 1 , wherein said peptide has the ability to bind to an 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, and wherein said variant binds to molecule(s) of the major histocompatibility complex (MHC) and/or induces T cells cross-reacting with said variant peptide.

3 . The peptide or variant thereof according to claim 1 , wherein the amino acid sequence thereof comprises a continuous stretch of amino acids comprising SEQ ID No. 38.

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 amino acids.

5 . The peptide or variant thereof according to claim 4 , wherein said peptide or variant thereof has an overall length of from 8 to 30.

6 . The peptide or variant thereof according to claim 4 , wherein said peptide or variant thereof has an overall length of from 8 to 16 amino acids.

7 . The peptide or variant thereof according to claim 4 , wherein the peptide consists or consists essentially of SEQ ID No. 38.

8 . The peptide or variant thereof according to claim 1 , wherein said peptide is modified and/or includes non-peptide bonds.

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

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

11 . An expression vector capable of expressing the nucleic acid according to claim 10 .

12 . A recombinant host cell comprising the peptide according to claim 1 .

13 . A recombinant host cell comprising the nucleic acid according to claim 10 .

14 . A recombinant host cell comprising the expression vector according to claim 11 , wherein said host cell is optionally an antigen presenting cell.

15 . The recombinant host cell of claim 14 , wherein said antigen presenting cell is a dendritic cell.

16 . A method for producing a peptide comprising SEQ ID No. 38 or variant thereof, the method comprising culturing the host cell according to claim 12 , and isolating the peptide or variant thereof from the host cell or its culture medium.

17 . 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 .

18 . An activated T lymphocyte, produced by the method according to claim 17 , that selectively recognizes a cell which presents a polypeptide comprising SEQ ID No. 38 or variant thereof.

19 . A method for killing target cells in a patient which target cells present a polypeptide comprising the amino acid sequence of SEQ ID No. 38 or variant thereof, the method comprising administering to the patient an effective number of activated T lymphocytes as defined in claim 18 .

20 . An antibody that specifically recognizes the peptide or variant thereof according to claim 1 .

21 . The antibody of claim 20 , wherein the antibody is a soluble or membrane-bound antibody.

22 . The antibody of claim 20 , wherein the antibody specifically recognizes the peptide or variant thereof according to claim 1 when bound to an MHC molecule.

23 . The antibody according to claim 20 , wherein the antibody carries a further effector function such as an immune stimulating domain or toxin

24 . A method of using a peptide according to claim 1 for the treatment of cancer or in the manufacture of a medicament against cancer.

25 . The method according to claim 24 , wherein said cancer is selected from the group of lung cancer, brain cancer, gastric cancer, colorectal cancer, hepatic cancer, pancreatic cancer, prostate cancer, leukemia, breast cancer, melanoma, ovarian cancer, esophageal cancer and other tumors that show an overexpression of a protein from which peptide SEQ ID No. 38 is derived from.

26 . A kit comprising:
(a) a container comprising a pharmaceutical composition containing the peptide(s) or the variant according to claim 1 , in solution or in lyophilized form; and (b) wherein the kit optionally comprises one or more of a buffer, a diluent, a filter, a needle, instructions for use of the solution or reconstitution and/or use of the lyophilized formulation, or a syringe.

27 . A method for producing a personalized anti-cancer vaccine, said method comprising:
a) identifying tumor-associated peptides (TUMAPs) presented by a tumor sample from said individual patient; b) comparing the peptides as identified in a) with a warehouse of peptides that have been pre-screened for immunogenicity and/or over-presentation in tumors as compared to normal tissues; c) selecting at least one peptide from the warehouse that matches a TUMAP identified in the patient; and d) formulating the personalized vaccine or compound or cellular therapy based on step c).

28 . The method according to claim 27 , wherein said TUMAPs are identified by:
a1) comparing expression data from the tumor sample to expression data from a sample of normal tissue corresponding to the tissue type of the tumor sample to identify proteins that are over-expressed or aberrantly expressed in the tumor sample; and a2) correlating the expression data with sequences of MHC ligands bound to MHC class I and/or class II molecules in the tumor sample to identify MHC ligands derived from proteins over-expressed or aberrantly expressed by the tumor.

29 . The method according to claim 27 , wherein the sequences of MHC ligands are identified by eluting bound peptides from MHC molecules isolated from the tumor sample, and sequencing the eluted ligands.

30 . The method according to claim 27 , wherein the normal tissue corresponding to the tissue type of the tumor sample is obtained from the same patient.

31 . The method according to claim 27 , wherein the peptides included in the warehouse are identified based on the following steps:
aa. Performing genome-wide messenger ribonucleic acid (mRNA) expression analysis by highly parallel methods, such as microarrays or sequencing-based expression profiling, comprising identify genes that over-expressed in a malignant tissue, compared with a normal tissue or tissues; ab. Selecting peptides encoded by selectively expressed or over-expressed genes as detected in step aa, and ac. Determining an induction of in vivo T-cell responses by the peptides as selected comprising in vitro immunogenicity assays using human T cells from healthy donors or said patient; or ba. Identifying HLA ligands from said tumor sample using mass spectrometry; bb. Performing genome-wide messenger ribonucleic acid (mRNA) expr

Assignees

• Immatics Biotechnologies Gmbh

Inventors

• Mahr Andrea
• Weinschenk Toni
• Schoor Oliver
• Fritsche Jens
• Singh Harpreet
• Song Colette

Classifications

• A61P35/00

  Antineoplastic agents · CPC title

• C12N2310/16

  Aptamers · CPC title

• C07K14/70539 Primary

  MHC-molecules, e.g. HLA-molecules · CPC title

• A61K2039/505

  comprising antibodies · CPC title

• C07K16/2833

  against MHC-molecules, e.g. HLA-molecules · CPC title