Folate Receptor 4 Detection of Regulatory T Cells
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Solution Overview
Problem
Current methods fail to accurately distinguish and isolate regulatory T cells (Treg cells) from activated T cells in a live state, and there is no technique for selectively reducing Treg cells in vivo, which hinders clinical applications such as treating malignant tumors, infectious diseases, and suppressing immunity after organ transplantation.
Innovation Solution
The method involves using folate receptor 4 as a surface indicator to detect and isolate Treg cells, employing anti-folate receptor 4 antibodies or fragments to specifically target and reduce Treg cells, thereby enhancing immune response and treating diseases.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Measurement precision
If CD25 or GITR is used as an indicator to distinguish Treg cells from activated T cells, then Treg cells can be identified, but the distinction accuracy deteriorates because these markers are also highly expressed on activated T cells
Solution Approach 1:
The patent segments the detection process into multiple independent marker evaluations. Instead of relying on a single marker like CD25 or GITR that causes false positives, the invention uses a combination of markers (Foxp3, CTLA-4, PD-1, LAG-3, TIGIT) to progressively refine and accurately identify Treg cells, thereby resolving the contradiction between detection capability and false positive rates
Solution Approach 2:
The patent employs multiple markers that serve different functions in Treg cell identification. Foxp3 provides nuclear transcriptional evidence, while surface markers like CTLA-4, PD-1, LAG-3, and TIGIT provide complementary phenotypic information. This multi-functional marker panel ensures accurate Treg cell detection without the false positives associated with single-marker approaches
2Measurement precision
If Foxp3 is used as an indicator to isolate Treg cells, then specific detection is improved, but the ability to isolate live Treg cells deteriorates because Foxp3 is a transcription factor not expressed on the cell surface
Solution Approach 1:
The patent uses surface markers (CTLA-4, PD-1, LAG-3, TIGIT) as intermediaries that correlate with Foxp3 expression. These surface markers serve as accessible proxies for the intracellular Foxp3 transcription factor, enabling live cell isolation via surface staining while maintaining the specificity associated with Foxp3-based identification
Solution Approach 2:
The patent transitions from intracellular detection (Foxp3 in nucleus) to surface detection (CTLA-4, PD-1, LAG-3, TIGIT on cell membrane). This dimensional shift from internal to external markers enables live cell isolation while preserving the specificity of Foxp3-based Treg cell identification through correlated surface expression patterns
3Device complexity
If no specific technique is available to reduce Treg cells in vivo, then the complexity of immunotherapy is reduced, but the effectiveness of treating malignant tumors and infectious diseases deteriorates due to suppressed immune response
Solution Approach 1:
The patent extracts and removes Treg cells from the immune system through specific depletion techniques. By isolating and eliminating Treg cells that suppress immune responses, the invention enables effective anti-tumor and anti-infectious disease immunity while maintaining a relatively simple therapeutic approach
Solution Approach 2:
The patent applies preliminary depletion of Treg cells before administering activated T cells or immunotherapies. This pre-action removes the suppressive barrier that would otherwise undermine subsequent immune activation, ensuring therapeutic effectiveness without requiring complex multi-step protocols
4Power
If activated T cells are administered to treat diseases, then immune response is enhanced, but the effectiveness deteriorates because Treg cells suppress the activity of activated T cells
Solution Approach 1:
The patent applies preliminary depletion of Treg cells before administering activated T cells. By removing the suppressive Treg population in advance, the invention prevents the harmful immunosuppressive action that would otherwise counteract the therapeutic activated T cells, thereby ensuring enhanced immune response effectiveness
Solution Approach 2:
The patent converts the harmful immunosuppressive function of Treg cells into a beneficial therapeutic outcome by selectively depleting them. The removal of Treg cells, which normally suppress immunity, transforms them from harmful suppressors into beneficial contributors to enhanced anti-tumor and anti-infectious disease immune responses
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
This approach allows for effective detection, isolation, and reduction of Treg cells, stimulating immunity and treating tumors or infectious diseases by enhancing the action of activated T cells, and can be used to suppress immunity after organ transplantation.
Implementation Method 1
measuring expressions of folate receptor 4 on the surfaces of the test cells and detecting regulatory T cells using the expressions as an indicator
Implementation Method 2
employing anti-folate receptor 4 antibodies or fragments to specifically target and reduce Treg cells
Data Source
AI summary
An object of the present invention is to provide a technique to distinguish between Treg cells and activated T cells in a live state. Another object of the present invention is to provide a pharmaceutical composition for immunostimulation that can reduce the number of Treg cells in vivo and effectively express the immune response of activated T cells. In the method of the present invention, Treg cells are detected from test cells containing (i) regulatory T cells and (ii) at least one type of cell selected from the group consisting of naive T cells and activated T cells, wherein expressions of folate receptor 4 on the surfaces of cells are measured and Treg cells are detected using the expressions as an indicator. The present invention uses anti-folate receptor 4 antibody or folate receptor 4-binding fragment as an active ingredient contained in a pharmaceutical composition for immunostimulation.