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

Patent metadata

Field	Value
Publication number	US-2017165337-A1
Application number	US-201615374054-A
Country	US
Kind code	A1
Filing date	Dec 9, 2016
Priority date	Dec 10, 2015
Publication date	Jun 15, 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 selected from the group consisting of SEQ ID No. 1 to SEQ ID No. 385, and variant sequences thereof which are at least 88% homologous to SEQ ID No. 1 to SEQ ID No. 385, 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. 1 to SEQ ID No. 385.

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 sequence according to the group of SEQ ID No. 1 to SEQ ID No. 385.

5 . The peptide comprising an amino acid sequence selected from the group consisting of SEQ ID No. 1 to SEQ ID No. 385, and variant sequences thereof which are at least 88% homologous to SEQ ID No. 1 to SEQ ID No. 385, 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, wherein said peptide is modified and/or includes non-peptide bonds.

6 . 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).

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

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

9 . A recombinant host cell comprising the 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, wherein said host cell optionally is an antigen presenting cell optionally a dendritic cell.

10 . 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.

11 . 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.

12 . 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 .

13 . An activated T cell, optionally an activated T lymphocyte, produced by the method according to claim 12 , that selectively recognizes a cell which presents a polypeptide comprising an amino acid sequence selected from the group consisting of SEQ ID No. 1 to SEQ ID No. 385, and variant sequences thereof which are at least 88% homologous to SEQ ID No. 1 to SEQ ID No. 385.

14 . A method for killing target cells in a patient which target cells present a polypeptide comprising an amino acid sequence selected from the group consisting of SEQ ID No. 1 to SEQ ID No. 385, and variant sequences thereof which are at least 88% homologous to SEQ ID No. 1 to SEQ ID No. 385, the method comprising administering to the patient an effective number of activated T cells as defined in claim 13 .

15 . 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.

16 . 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 capable of being used in the treatment of cancer or in the manufacture of a medicament against cancer, or in a diagnostic method for detection of cancerous cells.

17 . The peptide or variant according to claim 16 , wherein said cancer is selected from the group of lung cancer, kidney cancer, brain cancer, stomach cancer, colon or rectal cancer, liver cancer, prostate cancer, leukemia, breast cancer, Merkel cell carcinoma (MCC), melanoma, ovarian cancer, esophageal cancer, urinary bladder cancer, endometrial cancer, gall bladder cancer, and bile duct cancer, and other tumors that show an overexpression of a protein comprising a peptide sequence of any of SEQ ID No. 1 to SEQ ID No. 385.

18 . 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 selected from the group consisting of SEQ ID No. 1 to SEQ ID No. 522, and (d) optionally, instructions for (i) use of the solution or (ii) reconstitution and/or use of the lyophilized formulation.

19 . The kit according to claim 18 , further comprising one or more of (iii) a buffer, (iv) a diluent, (v) a filter, (vi) a needle, or (v) a syringe.

20 . The kit according to claim 18 , wherein said peptide is selected from the group consisting of SEQ ID No. 1 to SEQ ID No. 385.

21 . A method for producing a personalized anti-cancer vaccine for the use as a compound-based and/or cellular therapy for an individual patient, said method comprising:
a) identifying tumor-associated peptides (TUMAPs) presented by a tumor sample from the 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, wh

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

• A61P25/00

  Drugs for disorders of the nervous system · CPC title

• A61P1/18

  for pancreatic disorders, e.g. pancreatic enzymes · CPC title