CAR-Treg Fusion Protein for Localized IBD Immune Suppression
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Solution Overview
Problem
Current treatments for inflammatory bowel disease, such as Morbus Crohn and Colitis ulcerosa, often cause systemic immune suppression, which is undesirable and can have widespread side effects.
Innovation Solution
A fusion protein, specifically a chimeric antigen receptor (CAR) is developed that is activated by meprin 1α (MEP1A) and cadherin 17 (CDH17) antigens, expressed in regulatory T-cells (Treg) to provide localized immune suppression at the site of inflammation, using a nucleic acid construct for genetic manipulation.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Reliability
If conventional immune suppression treatments are used for inflammatory bowel disease, then immune response is suppressed, but systemic immune suppression occurs causing widespread side effects
Solution Approach 1:
The patent applies local quality by engineering Treg cells to express CAR molecules with scFv domains that specifically recognize intestinal antigens (MEP1A or CDH17). This confers localized suppressive activity exclusively at the intestinal inflammation site, while preserving systemic immune function. The localized action is achieved through antigen-specific recognition that restricts Treg activation and suppressive function to tissues expressing the target antigens.
Solution Approach 2:
The patent uses CAR-expressing Treg cells as intermediaries that bridge the gap between systemic immune regulation and local inflammation control. These engineered Tregs circulate systemically but only become activated and exert suppressive effects when encountering their specific intestinal antigens at the inflammation site, thus mediating localized immune suppression without systemic side effects.
2Object-affected harmful factors
If CAR is expressed in Treg cells to provide localized immune suppression, then systemic side effects are reduced, but the complexity of the treatment increases
Solution Approach 1:
The patent achieves universality by using a modular CAR construct design that can be adapted to target different intestinal antigens (MEP1A, CDH17, or other gut-specific antigens) while maintaining the same Treg cell platform. This universal approach allows the same engineered Treg system to treat different types of inflammatory bowel disease or different disease locations, reducing overall treatment complexity despite the sophisticated mechanism.
Applied Scientific Principles
This section explains which scientific principles are used to turn an abstract innovation direction into a practical engineering solution.
Function Achieved in This Case
The CAR-expressing Treg cells selectively suppress immune responses at the site of bowel inflammation, minimizing systemic immune suppression and targeting the disease locally, thereby reducing side effects.
Implementation Method 1
the scFv domain specific for being activated by the location of inflammatory bowel disease, especially binding to one of meprin 1α (MEP1A) and cadherin 17 (CDH17)
Data Source
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AI summary
The invention provides a fusion protein, a nucleic acid construct encoding the fusion protein and regulatory T-cells (Treg) expressing the fusion protein for use in the treatment of inflammatory bowel disease, wherein the fusion protein is a chimeric antigen receptor (CAR) having a single chain variable fragment (scFv) domain specific for being activated by the location of inflammatory bowel disease, especially binding to one of meprin 1α (MEP1A) and cadherin 17 (CDH17), a transmembrane domain and at least one intracellular signalling domain. The scFv domains specific for MEP1A or CDH17 have been found to selectively bind to intestine afflicted by inflammatory bowel disease and to activate suppressive activity in Treg expressing the CAR at the location of inflammatory bowel disease. Specifically, the invention provides a CAR for use in the treatment of an immune response, e.g. in the treatment of an autoimmune response, which is directed against MEP1A or directed against CDH17.