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Epigenetic modification of the loci for CAMTA1 and/or FOXP3 as a marker for cancer treatment

a technology of camta1 and foxp3 is applied in the field of epigenetic modification of camta1 and/or foxp3 as a marker for cancer treatment, which can solve the problem of unfavorable prognostic indicators such as high prevalence of tregs infiltrating hcc, and achieve the effect of diagnosing the survival of a cancer patien

Pending Publication Date: 2007-10-18
PRECISION FOR MEDICINE GMBH
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Benefits of technology

[0021] The present invention relates to a method, in particular an in vitro method, for pan-cancer diagnostics, comprising identifying the amount and / or proportion of stable regulatory T cells in a patient suspected of having cancer through analyzing the methylation status of at least one CpG position in the gene foxp3 and / or the gene camta1 or orthologous or paralogous genes thereof, wherein an increased amount and / or proportion of stable regulatory T cells in said patient is indicative for an unspecific cancerous disease. In a second aspect thereof, the present invention relates to a method for diagnosing the survival of a cancer patient, comprising identifying the amount and / or proportion of stable regulatory T cells in said cancer patient through analyzing the methylation status of at least one CpG position in the gene foxp3 and / or the gene camta1 or orthologous or paralogous genes thereof, wherein a demethylation in the gene foxp3 and / or the gene camta1 or orthologous or paralogous genes thereof, is indicative of a stable regulatory T cell, and wherein an increased amount and / or proportion of stable regulatory T cells in said cancer patient is indicative for a shorter survival for said cancer patient. Furthermore, the present invention relates to an improved treatment of cancers based on the inventive methods, and a kit for performing the above methods as well as respective uses.

Problems solved by technology

A high prevalence of Tregs infiltrating HCC is described to be an unfavorable prognostic indicator.

Method used

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  • Epigenetic modification of the loci for CAMTA1 and/or FOXP3 as a marker for cancer treatment
  • Epigenetic modification of the loci for CAMTA1 and/or FOXP3 as a marker for cancer treatment
  • Epigenetic modification of the loci for CAMTA1 and/or FOXP3 as a marker for cancer treatment

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Mice

[0086] BALB / c mice were bred at the BfR (Bundesinstitut fuer Risikobewertung, Berlin, Germany) and used at 6-12 wk of age. All animal experiments were performed under specific pathogen free conditions and in accordance with institutional, state and federal guidelines.

Antibodies, Staining Reagents and Cytokines

[0087] The following antibodies were produced in the inventors' laboratory: anti FcR II / III (2.4G2), anti CD4 (GK1.5), anti CD3 (145.2C11), anti CD28 (37.51) and anti IL-4 (11B11). The following antibodies and secondary reagents were purchased from BD PharMingen: anti CD4 (RM4-5), anti CD19 (1D3), anti CD25 (7D4), anti CD8 (53-6.7), anti CD25 (PC6.1), anti CD62L (Mel-14), streptavidin, and appropriate isotype controls. The PE anti-mouse Foxp3 staining set was purchased from eBioscience. All microbeads were obtained from Miltenyi Biotec and all cytokines from RandD systems.

Flow Cytometry

[0088] Cytometric analysis was performed as previously described (Huehn, J. et al...

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Abstract

The present invention relates to a method, in particular an in vitro method, for pan-cancer diagnostics, comprising identifying the amount and / or proportion of stable regulatory T cells in a patient suspected of having cancer through analyzing the methylation status of at least one CpG position in the gene foxp3 and / or the gene camta1 or orthologous or paralogous genes thereof, wherein an increased amount and / or proportion of stable regulatory T cells in said patient is indicative for an unspecific cancerous disease. In a second aspect thereof, the present invention relates to a method for diagnosing the survival of a cancer patient, comprising identifying the amount and / or proportion of stable regulatory T cells in said cancer patient through analyzing the methylation status of at least one CpG position in the gene foxp3 and / or the gene camta1 or orthologous or paralogous genes thereof, wherein a demethylation in the gene foxp3 and / or the gene camta1 or orthologous or paralogous genes thereof, is indicative of a stable regulatory T cell, and wherein an increased amount and / or proportion of stable regulatory T cells in said cancer patient is indicative for a shorter survival for said cancer patient. Furthermore, the present invention relates to an improved treatment of cancers based on the inventive methods, and a kit for performing the above methods as well as respective uses.

Description

CROSS-REFERENCE TO RELATED APPLICATION [0001] This application claims the benefit of U.S. Provisional Application Ser. No. 60 / 777,631, filed Feb. 28, 2006, which is hereby incorporated by reference in its entirety, including any figures, tables, nucleic acid sequences, and amino acid sequences.BACKGROUND OF THE INVENTION [0002] Regulatory T cells play an important role for the maintenance of immunological tolerance by suppressing the action of autoreactive effector cells, making them interesting targets for therapeutic applications. Therefore, these cells are critically involved in preventing the development of autoimmune reactions (Sakaguchi, Nat Immunol 6:345-352, 2005). [0003] Regulatory T cells (Tregs), which have been shown to play a pivotal role in the maintenance of self-tolerance within the immune system, were described originally as CD4+ T cells constitutively expressing CD25 (Sakaguchi, S. Naturally arising CD4+ regulatory T cells for immunologic self-tolerance and negativ...

Claims

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Application Information

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Patent Type & Authority Applications(United States)
IPC IPC(8): A61K39/395A61K31/7052A61P35/00C12Q1/68A61K38/20
CPCC12Q1/6886C12Q2600/154C12Q2600/118A61P35/00
Inventor OLEK, SVEN
Owner PRECISION FOR MEDICINE GMBH
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