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TGFBETA INHIBITOR CONTAINING REIC/Dkk-3 PROTEIN AS ACTIVE INGREDIENT

A β inhibitor, dkk-3 technology, applied in the field of TGFβ inhibitors

Inactive Publication Date: 2019-03-01
MOMOTARO GENE INC (JP)
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

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Problems solved by technology

However, the effective rate of existing immune checkpoint inhibitors (anti-PD-1 antibodies) is 20 to 30%, and it is expected that biopharmaceuticals that block multiple action points at the same time to further improve the efficiency

Method used

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  • TGFBETA INHIBITOR CONTAINING REIC/Dkk-3 PROTEIN AS ACTIVE INGREDIENT
  • TGFBETA INHIBITOR CONTAINING REIC/Dkk-3 PROTEIN AS ACTIVE INGREDIENT
  • TGFBETA INHIBITOR CONTAINING REIC/Dkk-3 PROTEIN AS ACTIVE INGREDIENT

Examples

Experimental program
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Embodiment

[0081] The present invention will be specifically described by the following examples, but the present invention is not limited by these examples.

[0082] 1. Research on the protein binding to REIC protein

[0083] Take advantage of Free Style TM293 cells are used as the host secretory expression system to produce full-length REIC protein and use ion exchange chromatography for high-purity separation and purification. This sample was mixed with NHS Mag Sepharose (GE Healthcare) to prepare REIC-immobilized magnetic beads. Next, add GM-CSF (10 ng / mL) and IL-4 (10 ng / mL) to commercially available CD14-positive human peripheral blood mononuclear cells (Lonza) at the same time, induce differentiation into dendritic cell-like cells, and culture for 6 days . This culture supernatant was mixed with REIC-immobilized magnetic beads at room temperature, and molecules bound to the beads were collected. The molecules bound to the magnetic beads were eluted with glycine / hydrochloric ac...

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Abstract

The purpose of the present invention is to provide a medicine for preventing or treating TGFbeta-related diseases by inhibiting signal transduction of TGFbeta. Provided are: a TGFbeta inhibitor that contains, as an active ingredient, the REIC / Dkk-3 protein, a partial protein including a Cys-rich domain thereof, or DNA encoding those; and a prophylactic or therapeutic agent for TGFbeta-related diseases, containing said TGFbeta inhibitor.

Description

technical field [0001] The invention relates to a TGFβ inhibitor that weakens the activity of transforming growth factor β (TGFβ) in tissues and organs, and can improve the condition of TGFβ-related diseases by inhibiting TGFβ. Background technique [0002] The secretory protein REIC, which is commonly expressed in most normal human tissues, loses its expression in most cancer cells. According to its discovery process, it was named as Reduced Expression in Immortalized Cell (REIC) protein in 2000. Further, it belongs to the Dickkopf (Dkk) family according to its structural characteristics, and its common name is called REIC / Dkk-3. When cancer cells are infected with an adenoviral vector (Ad-REIC) that forcibly expresses the REIC / Dkk-3 protein, apoptosis accompanied by endoplasmic reticulum stress is induced in the cancer cells. This induction of apoptosis is a phenomenon that is specific to cancer cells and cannot be observed in normal cells. Therefore, clinical research on...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): A61K38/02A61K48/00A61P1/04A61P1/16A61P9/00A61P9/12A61P11/00A61P13/12A61P19/02A61P21/02A61P25/02A61P25/16A61P25/28A61P29/00A61P35/00A61P35/02A61P43/00C07K14/47
CPCA61K38/1709A61K48/00A61P1/04A61P1/16A61P9/00A61P9/12A61P11/00A61P13/12A61P19/02A61P21/02A61P25/02A61P25/16A61P25/28A61P29/00A61P35/00A61P35/02A61P43/00C07K14/47C07K14/4703
Inventor 木下理惠二见淳一郎公文裕巳
Owner MOMOTARO GENE INC (JP)
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