CD8+ Regulatory T-Cell Selection for Gastrointestinal Inflammation
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Solution Overview
Problem
Current treatments for inflammatory bowel diseases (IBD) like Crohn's disease and ulcerative colitis often rely on anti-inflammatory medications that can have adverse reactions, and there is a lack of consistent correlation between Treg function and abundance in patient tissues, making it difficult to identify suitable Treg cells for cellular immunotherapy.
Innovation Solution
The identification of specific homing receptor expression patterns allows for the selection of CD8+ regulatory T-cells that can migrate to and localize in the gastrointestinal tract, specifically targeting diseased tissues, enabling their use in therapeutic compositions for treating inflammatory and autoimmune diseases.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Reliability
If anti-inflammatory medications are used to treat IBD, then inflammation is reduced, but adverse reactions occur and patients need to reduce dose or taper completely
Solution Approach 1:
The patent extracts and isolates the beneficial immunosuppressive function from the harmful systemic effects by using specifically selected Treg cells that target only the inflamed gastrointestinal tissues through tissue-specific homing receptors, rather than using systemic anti-inflammatory medications that affect the entire body
Solution Approach 2:
The patent applies local quality by engineering Treg cells with specific homing receptors (such as CCR9 for small intestine, CCR10 for colon) that enable these cells to selectively migrate to and accumulate in the inflamed gastrointestinal tissues, providing localized immunosuppression exactly where needed without systemic side effects
2Ease of manufacture
If Treg cells are used for cellular immunotherapy, then targeted treatment is achieved, but there is lack of consistent correlation between Treg function and abundance in patient tissues making identification difficult
Solution Approach 1:
The patent changes the identification parameters from relying on traditional Treg markers (CD4, FOXP3) that show inconsistent correlation with function, to using tissue-specific homing receptor expression patterns (CCR9, CCR10, alpha4beta7 integrin) that precisely identify Treg cells capable of migrating to specific inflamed tissues, thereby improving identification accuracy and functional correlation
3Object-affected harmful factors
If Teff migration to intestinal tissues is blocked through pharmaceutical blockade of adhesion molecules or chemoattractants, then T-cell migration is inhibited, but success is mixed
Solution Approach 1:
Instead of blocking Teff migration to intestinal tissues (the conventional approach with mixed success), the patent inverts the strategy by actively promoting Treg cell migration to the same tissues through enhanced expression of tissue-specific homing receptors, thereby achieving immunosuppression through positive recruitment of regulatory cells rather than negative blocking of effector cells
Data Source
AI summary
The present invention relates to composition comprising an isolated CD8+ Treg cell population, wherein the Treg cells have signatures for i) identifying that the T-cells are CD8+ regulatory Tcells, ii) identifying that the Treg cells are tissue type tropic, i.e they can migrate to the diseased tissue, iii) optionally identifying that the Treg cells are tropic with respect to the diseased tissue, i.e. they are homing cells, iv) identifying that the Treg cells are emigrant cells, i.e. they originate from the target tissue, and v) optionally identifying that the Treg cells are capable of being retained in the target tissue and optionally one or more X-signatures and/or one or more Y-signatures.