Means and methods for treating or diagnosing IDH1 R132H mutant-positive cancers

Patent metadata

Field	Value
Publication number	US-10161940-B2
Application number	US-201314370224-A
Country	US
Kind code	B2
Filing date	Jan 3, 2013
Priority date	Jan 5, 2012
Publication date	Dec 25, 2018
Grant date	Dec 25, 2018

Abstract

The present invention concerns the field of tumor therapeutics and diagnostics. Specifically, it relates to a peptide comprising at least 8 amino acids in length which are present as contiguous amino acid sequence in the human Isocitratdehydrogenase Type 1 (IDH1), wherein said peptide has at least one amino acid exchange from R to H at a position corresponding to position 132, for use in preventing and/or treating cancer. Further contemplated is a medicament comprising the said peptide. Furthermore, the invention relates to a method for diagnosing cancer characterized by having a mutation in the genome of at least some cancer cells which results in the expression of a mutant IDH1 having the R132H mutation comprising the steps of contacting a blood sample of a subject suspected to suffer from such a cancer with a peptide comprising at least 10 amino acids in length which are present as contiguous amino acid sequence in the IDH1, wherein said peptide has at least one amino acid exchange from R to H at a position corresponding to position 132 for a time and under conditions which allow for specific binding of a component of the immune system to the peptide, and determining whether, or not, binding of the said component of the immune system to the peptide occurred, wherein the cancer is diagnosed if the occurrence of binding has been determined. Provided by the invention is also a kit and a device for carrying out said method.

First claim

The invention claimed is:

1. A medicament comprising
a peptide selected from the group consisting of
an amino acid sequence consisting of the amino acids corresponding to SEQ ID NO: 1;
an amino acid sequence consisting of the amino acids corresponding to SEQ ID NO: 2; and
an amino acid sequence consisting of the amino acids corresponding to SEQ ID NO: 9, and

a pharmaceutically acceptable carrier selected from the group consisting of terra alba, sucrose, talc, gelatin, agar, pectin, acacia, stearic acid, syrup, glyceryl mono-stearate, glyceryl mono-stearate with a wax, glyceryl distearate, and glyceryl distearate with a wax.

2. The medicament of claim 1 , wherein the peptide consists of the amino acid sequence of SEQ ID NO: 9.

3. A device for diagnosing cancer having a mutation in the genome of at least some cancer cells which results in the expression of a mutant IDH1 having the R132H mutation, comprising:
a) an analyzing unit comprising
a peptide selected from the group consisting of
an amino acid sequence consisting of the amino acids corresponding to SEQ ID NO: 1;
an amino acid sequence consisting of the amino acids corresponding to SEQ ID NO: 2; and
an amino acid sequence consisting of the amino acids corresponding to SEQ ID NO: 10;
arranged for detection of a component of the immune system in a sample of a subject; and

a detection agent capable of generating a detectable signal and binding a complex comprising said peptide and the component of the immune system; and

b) an evaluation unit comprising a detector capable of detecting specific binding of the component of the immune system to the said peptide,
wherein said detector generates an output signal indicating whether a specific binding of the component to the peptide occurs,
wherein the component is a T-lymphocyte, a B-lymphocyte, or a dendritic cell, and
wherein the cancer is a glioma.

4. The device of claim 3 , wherein the peptide consists of the amino acid sequence of SEQ ID NO: 10.

5. A kit for diagnosing cancer having a mutation in the genome of at least some cancer cells which results in expression of a mutant IDH1 having the R132H mutation, comprising
instructions for carrying out said method,
a peptide selected from the group consisting of
an amino acid sequence consisting of the amino acids corresponding to SEQ ID NO: 1;
an amino acid sequence consisting of the amino acids corresponding to SEQ ID NO: 2;
an amino acid sequence consisting of the amino acids corresponding to SEQ ID NO: 10; and

a detection agent capable of generating a detectable signal and binding a complex comprising said peptide and a component of the immune system,
wherein the component is a T-lymphocyte, a B-lymphocyte or a dendritic cell, and
wherein the cancer is a glioma.

6. The kit of claim 5 , wherein the peptide consists of the amino acid sequence of SEQ ID NO: 10.

7. A method for diagnosing cancer having a mutation in the genome of at least some tumor cells, which result in expression of a mutant IDH1 having the R132H mutation, comprising:
a) contacting a blood sample of a subject suspected to suffer from such a cancer with a peptide selected from the group consisting of
an amino acid sequence consisting of the amino acids corresponding to SEQ ID NO: 1;
an amino acid sequence consisting of the amino acids corresponding to SEQ ID NO: 2; and
an amino acid sequence consisting of the amino acids corresponding to SEQ ID NO: 10;
which allow for specific binding of a cell of the immune system in the blood sample to the peptide;

b) isolating an IFN-γ producing cell from the blood sample contacted with the peptide;
c) providing a detection agent capable of generating a detectable signal for binding a complex comprising said peptide and the IFN-γ producing cell of the immune system;
d) determining whether binding of said IFN-γ producing cell of the immune system to the peptide occurs by measuring the level of the detectable signal,
wherein the cancer is diagnosed if the level of the detectable signal is greater than a pre-determined level, and
wherein the cancer is a glioma.

8. The method of claim 7 , wherein said cell of the immune system is a lymphocyte.

9. The method of claim 7 , wherein said glioma is selected from the group consisting of WHO II or WHO III astrocytoma, oligodendroglioma, oligoastrocytoma, glioblastoma and gliosarcoma.

10. The method of claim 7 , wherein the peptide consists of the amino acid sequence of SEQ ID NO: 10.

Assignees

• Deutsches Krebsforsch
• Ruprecht Karls Univ
• Ruprecht Karls Univeristaet Heidelberg

Inventors

• Platten Michael
• Bunse Theresa
• Wick Wolfgang

Classifications

• A61P35/02

  specific for leukemia · CPC title

• A61P35/00

  Antineoplastic agents · CPC title

• G01N33/57557

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

• G01N33/57505

  of the blood, e.g. leukaemia · CPC title

• G01N33/57595 Primary

  involving intracellular compounds · CPC title