CD8+ Treg Cell Identification via Migratory Marker Segmentation
Find Innovative SolutionsGenerate Solutions
Solution Overview
Problem
Current methods for treating inflammatory and autoimmune diseases, such as Crohn's disease, face challenges in identifying and utilizing CD8+ T-regulatory cells (Tregs) effectively due to limitations in understanding Treg origin and function, and the lack of consistent correlation with impaired Treg function or diminished abundance in patient tissues.
Innovation Solution
A method is developed to identify and select CD8+ Treg cells with specific migratory and functional characteristics for use in cellular immunotherapy, involving analysis of samples from target tissues and lymphatic tissues to isolate Treg populations that can migrate to and localize in diseased tissues, using surface and intracellular markers to define suitable Treg cells for therapeutic use.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Measurement precision
If conventional Treg identification methods are used, then general Treg populations can be isolated, but tissue-specific migratory characteristics cannot be identified
Solution Approach 1:
The patent segments Treg cell identification into multiple distinct marker categories: regulatory markers (FOXP3, CD25, CD127), migratory markers (α4β7, CCR9, CCR4), and tissue-specific markers. This segmentation allows simultaneous identification of both general Treg identity and specific migratory characteristics, resolving the contradiction between general identification and specific characteristic preservation.
Solution Approach 2:
The patent adds a new dimension of analysis by introducing migratory marker expression as an additional classification criterion beyond traditional regulatory markers. This multi-dimensional approach enables differentiation of Treg subsets based on their migratory potential to specific tissues, thereby preserving migratory characteristic information while maintaining accurate Treg identification.
2Ease of operation
If Treg cells are isolated from peripheral blood, then easy access is achieved, but tissue-specific Treg populations cannot be obtained
Solution Approach 1:
The patent replaces mechanical/t physical isolation methods with molecular marker-based identification. By using specific surface and intracellular markers (α4β7, CCR9, FOXP3) that are expressed on tissue-specific Treg cells, the method substitutes physical separation with molecular recognition, enabling precise isolation of tissue-specific populations from peripheral blood without complex mechanical procedures.
Solution Approach 2:
The patent changes the identification parameters from general Treg markers to a combination of regulatory markers and tissue-specific migratory markers. This parameter change enables the isolation of tissue-specific Treg populations from peripheral blood by selecting cells that express both FOXP3 (regulatory function) and tissue-specific homing receptors (migratory capability).
3Reliability
If CD4+ Tregs are used for therapy, then regulatory function is achieved, but CD8+ Treg-specific tissue targeting cannot be utilized
Solution Approach 1:
The patent applies universality by identifying a marker combination (FOXP3 + tissue-specific migratory markers) that can define regulatory T cells across different lineages (both CD4+ and CD8+). This universal approach allows the same identification strategy to be applied to both conventional and unconventional Treg subsets, enabling versatile tissue targeting while maintaining reliable immune regulation function.
Solution Approach 2:
Instead of starting with CD4+ Tregs as the conventional approach, the patent inverts the perspective by focusing on CD8+ T cells that express regulatory markers and tissue-specific migratory markers. This inversion allows utilization of CD8+ Treg-specific tissue targeting capabilities while maintaining regulatory function, thereby expanding therapeutic adaptability.
Data Source
Figure 1A~1E
Figure 2A~2C
Figure 3A~3C
AI summary
The present invention relates to a method for identifying CD8+ Treg cells suitable for use as starting material in cellular immunotherapy, the method comprising i) analysing samples from target tissue A to identify CD8+ Treg cells with migratory character between the diseased tissue, collecting lymphatics, peripheral blood, distinct tissue adjacent to the diseased target tissue A and/or distinct tissue that is not vicinal though has migratory Treg communication with target tissue A, v) analysing samples from peripheral blood, tissue C, to identify CD8+ Treg cells with migratory character and/or functional character where the Treg cells are also emigrant from target tissue A, vi) analysing sample(s) from tissue compartments A and/or B and C, that are analytically or physically depleted of emigrants from thymus and/or immigrants from peripheral blood to a lymph node, to restrict analyses to CD8+ Treg cells of target tissue A origin and/or tropism, to identify emigrant CD8+ Treg cell populations of target tissue A, to identify emigrant CD8+ Treg cell populations with propensity to immigrate to target tissue A, to identify a migratory and/or functional defect in the CD8+ Treg cell population identified as expressing migratory and/or functional elements specific for target tissue A in any of tissue A, B or C, and whereby a combination of surface or intracellular markers on CD8+ Treg cells is identified, which combination identifies which surface or intracellular markers should be present and which surface markers should not be present in CD8+ Treg cell populations suitable for use as starting material in cellular immunotherapy.