Engineered T Regulatory Cells for Targeted Inflammation Therapy
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Solution Overview
Problem
Current therapies for inflammatory and neuroinflammatory diseases lack precision and specificity, often causing unintended side effects and failing to effectively target severe inflammatory conditions, particularly neurodegenerative diseases.
Innovation Solution
Development of a biological targeting system using transgenic T regulatory cells expressing a targeting polypeptide that binds to tissue-specific markers, activating an effector polypeptide only upon specific tissue and disease conditions, thereby delivering anti-inflammatory effects precisely to inflamed tissues while sparing healthy tissue.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Reliability
If systemic or local delivery of anti-inflammatory drugs is used, then acute inflammation can be treated, but longer term and more severe inflammatory conditions are not effectively treated and unwanted side effects occur
Solution Approach 1:
The patent applies local quality by engineering T regulatory cells to express chimeric antigen receptors that specifically recognize inflammatory markers (such as IL-6, TNF-alpha, or IL-1beta) on inflamed tissues. This enables the cells to selectively accumulate and exert anti-inflammatory effects only at sites of chronic inflammation, while leaving healthy tissues unaffected. The targeted approach resolves the contradiction by providing effective treatment for severe inflammatory conditions without the systemic side effects associated with conventional anti-inflammatory drugs.
Solution Approach 2:
The patent uses T regulatory cells as intermediary carriers that are genetically modified to express chimeric antigen receptors. These engineered cells act as living mediators that specifically recognize and bind to inflammatory markers on target tissues, delivering anti-inflammatory effects in a controlled and targeted manner. This intermediary approach allows effective treatment of severe inflammatory conditions while avoiding the harmful side effects of systemic drug administration.
2Reliability
If existing anti-inflammatory drugs are used, then inflammation can be suppressed, but precision is lacking and health tissue immunocompetence is compromised
Solution Approach 1:
The patent implements local quality by designing T regulatory cells with chimeric antigen receptors that specifically recognize inflammatory markers (such as IL-6, TNF-alpha, or IL-1beta) expressed on inflamed tissues. This enables precise targeting of pathological inflammation while preserving immune function in healthy tissues. The engineered cells selectively accumulate at inflammatory sites through antigen-specific recognition, achieving high targeting precision that conventional drugs cannot provide.
Solution Approach 2:
The patent applies parameter changes by modifying the T regulatory cells through genetic engineering to express chimeric antigen receptors with specific binding affinities for inflammatory markers. By changing the molecular recognition parameters of the therapeutic cells, the patent achieves precise targeting of inflamed tissues based on the presence of specific inflammatory markers, thereby distinguishing between healthy and diseased states with high precision.
3Duration of action of stationary object
If T reg cells are engineered to express CAR, then persistence is improved, but therapeutic utility is still insufficient for severe inflammatory conditions
Solution Approach 1:
The patent enhances therapeutic efficacy by engineering T regulatory cells to express chimeric antigen receptors that specifically recognize inflammatory markers on target tissues. This local quality approach ensures that the persistent cells are actively recruited to and accumulate at sites of chronic inflammation through antigen-specific binding. The combination of improved persistence and targeted recruitment to inflamed tissues resolves the insufficiency of previous T reg cell therapies for severe inflammatory conditions.
Solution Approach 2:
The patent implements feedback mechanisms by designing T regulatory cells with chimeric antigen receptors that continuously sense and respond to inflammatory markers in the microenvironment. When inflammatory markers are detected, the engineered cells are activated and accumulate at the inflammatory site, exerting local anti-inflammatory effects. This feedback-driven response ensures that the persistent cells remain therapeutically active and adaptively respond to the inflammatory state, thereby achieving reliable therapeutic efficacy.
Data Source
AI summary
The invention relates to an artificial T cell receptor, wherein an antigen binding domain of the artificial T cell receptor specifically binds a complement pathway protein, nucleic acids encoding such artificial T cell receptors and cells engineered to express such nucleic acids. The invention also relates to targeting polypeptides comprising an extracellular ligand binding domain and an intracellular domain comprising a transcription factor, and wherein the transcription factor is configured to be released upon binding of the ligand binding domain by a ligand. The invention also relates to cells engineered to express the artificial T cell receptor and the targeting polypeptide, particularly where expression of the artificial T cell receptor is operatively linked to binding of the ligand binding domain. The cells of the invention are useful in medicine, particularly in the treatment of inflammatory conditions.