Histone anti-cancer vaccines

Patent metadata

Field	Value
Publication number	US-11767352-B2
Application number	US-202016832465-A
Country	US
Kind code	B2
Filing date	Mar 27, 2020
Priority date	Jul 15, 2015
Publication date	Sep 26, 2023
Grant date	Sep 26, 2023

Abstract

The present invention pertains to novel immunogenic peptide sequences that can be used as vaccines in the treatment of cancer diseases such as brain cancers and specifically glioma. The cancer vaccines of the invention are designed based on the K27M mutated variant of the human Histone 3. Provided are further fusion proteins comprising the sequences of the cancer vaccines, nucleic acids encoding such vaccines, such as RNA vaccines, and vectors and host cells comprising these sequences. Furthermore the invention pertains to T cells and T cell receptors binding the cancer vaccines of the invention, preferably when presented by the human Major Histocompatibility Complex (MHC). The peptide immunogens of the invention elicit a HLA restricted immune response and therefore are of use in the treatment of cancer diseases, in particular glioma. Further aspects of the invention pertain to pharmaceutical compositions as well as diagnostic methods based on the immunogenic capacity of the disclosed peptides.

First claim

The invention claimed is:

1. A method of treating a cancer characterized by the expression of the K27M mutated variant of human Histone H3.3 in a subject in need thereof, the method comprising the administration of an effective amount of a peptide comprising the amino acid sequence shown in SEQ ID NO: 13 or an amino acid sequence having a sequence identity of at least 95% to the sequence of SEQ ID NO: 13, wherein the peptide comprises the K27M mutated amino acid position and is not the full length K27M variant of human Histone H3.3.

2. The method according to claim 1 , wherein the peptide is capable of eliciting a T cell-mediated immune response in a mammal that is specific for the K27M variant of human Histone H3.3.

3. The method according to claim 1 , wherein the peptide consists of (i) the amino acid sequence of SEQ ID NO: 13 (KAPRKQLATKAARMSAPSTGGVKKPHR), or (ii) an amino acid sequence with a sequence identity of at least 95% to the sequence of SEQ ID NO: 13.

4. The method according to claim 1 , wherein the peptide is comprised in a fusion protein comprising an amino acid sequence composed of:
i) the amino acid sequences of at least two peptides, each peptide consisting of the amino acid sequence of SEQ ID NO: 13 (KAPRKQLATKAARMSAPSTGGVKKPHR), or
ii) the amino acid sequence of SEQ ID NO: 13, and the amino acid sequence of a heat shock protein (HSP) binding domain.

5. The method according to claim 1 , wherein the cancer characterized by the expression of the K27M mutated variant of human Histone H3.3 is selected from the group consisting of brain cancer, a cancer of the central nervous system, a glioma, an astrocytoma, and pediatric astrocytoma.

Assignees

• Deutsches Krebsforsch

Inventors

• Platten Michael
• Bunse Theresa
• Wick Wolfgang
• Ochs Katharina
• Ott Martina
• Bunse Lukas

Classifications

• G01N33/57595

  involving intracellular compounds · CPC title

• A61K2039/5158

  Antigen-pulsed cells, e.g. T-cells · CPC title

• A61K39/0011

  Cancer antigens · CPC title

• C07K14/47 Primary

  from mammals · CPC title

• A61K38/16

  Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof {(enzyme inhibitors A61K38/005)} · CPC title