Peptides and combination of peptides for use in immunotherapy against prostate cancer and other cancers

Patent metadata

Field	Value
Publication number	US-10799569-B2
Application number	US-201916552873-A
Country	US
Kind code	B2
Filing date	Aug 27, 2019
Priority date	Aug 5, 2015
Publication date	Oct 13, 2020
Grant date	Oct 13, 2020

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

The invention claimed is:

1. A method for producing an antibody specifically binding to a human major histocompatibility complex (MHC) class I molecule complexed with a HLA-restricted antigen consisting of the amino acid sequence of SEQ ID NO: 24, comprising:
(a) immunizing a genetically engineered non-human mammal comprising cells expressing said MHC class I molecule with a soluble form of a MHC class I molecule complexed with an HLA-restricted antigen consisting of the amino acid sequence of SEQ ID NO: 24;
(b) isolating mRNA molecules from antibody producing cells of said non-human mammal;
(c) producing a phage display library displaying protein molecules encoded by said mRNA molecules;
(d) isolating at least one phage from said phage display library,
wherein said at least one phage displaying said antibody specifically binding to said MHC class molecule complexed with an HLA-restricted antigen consisting of the amino acid sequence of SEQ ID NO: 24; and

(e) preparing said antibody using said phage display.

2. The method of claim 1 , wherein the antibody binds to said MHC class I molecule complexed with an antigen consisting of the amino acid sequence of SEQ ID NO: 24 with a binding affinity of below 20 nanomolar.

3. The method of claim 1 , further comprising humanizing the antibody.

4. The method of claim 1 , further comprising conjugating the antibody with a toxin.

5. The method of claim 1 , further comprising conjugating the antibody with an immune stimulating domain.

6. The method of claim 1 , wherein the antibody is a monoclonal antibody.

7. The method of claim 1 , further comprising modifying the antibody to a bi-specific antibody.

8. The method of claim 1 , further comprising modifying the antibody to a chimeric antibody.

9. The method of claim 1 , wherein the non-human mammal is mouse.

10. The method of claim 1 , wherein the MHC class I molecule is HLA-A*24.

11. The method of claim 1 , further comprising labeling the antibody with a radionucleotide.

12. The method of claim 11 , wherein the radionucleotide is selected from the group consisting of 111 In, 99 Tc, 14 C, 131 I, 3 H, 32 P, and 35 S.

13. The method of claim 1 , wherein the antibody has an affinity value (Kd) of less than 1×10 μM.

14. The method of claim 1 , further comprising modifying the antibody to an Fv.

15. The method of claim 1 , further comprising modifying the antibody to an Fab.

16. The method of claim 1 , further comprising modifying the antibody to an Fab′.

17. The method of claim 1 , wherein the antibody binds to said MHC class I molecule complexed with an antigen consisting of the amino acid sequence of SEQ ID NO: 24 with a binding affinity of below 10 nanomolar.

Assignees

• Immatics Biotechnologies Gmbh
• Immatics Biotechologies Gmbh

Inventors

• Mahr Andrea
• Weinschenk Toni
• Schoor Oliver
• Fritsche Jens
• Singh Harpreet
• Mueller Phillip
• Leibold Julia
• Goldfinger Valentina

Classifications

• G01N33/57557

  of other specific parts of the body, e.g. brain · CPC title

• G01N33/57575

  involving oncogenic proteins · CPC title

• G01N2570/00

  Omics, e.g. proteomics, glycomics or lipidomics; Methods of analysis focusing on the entire complement of classes of biological molecules or subsets thereof, i.e. focusing on proteomes, glycomes or lipidomes · CPC title

• C07K16/30

  from tumour cells · CPC title

• C12N2310/16

  Aptamers · CPC title