Anti-CD6 Antibody Modulation of T Cell Subsets
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Solution Overview
Problem
Current methods lack a specific cell surface biomarker to define and separate regulatory T cells (Treg cells) from other T cell subsets, making it difficult to selectively target subsets of T cells and modulate immune reactions effectively in autoimmune and inflammatory diseases.
Innovation Solution
The use of itolizumab, an anti-CD6 antibody, to selectively reduce cell surface CD6 levels on T-lymphocytes, thereby modulating the ratio of Teff to Treg cells and reducing pathogenic immune responses by administering optimized dosages based on monitoring CD6 levels in tissue samples.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Reliability
If current methods are used without a specific cell surface biomarker, then Treg cells cannot be selectively targeted, but this makes it difficult to modulate immune reactions effectively
Solution Approach 1:
The patent uses CD6 as an intermediary biomarker to indirectly identify and target Treg cells. Since Treg cells exhibit high CD6 expression (CD6high) during activation and pathogenic states, CD6 serves as a surrogate marker that enables selective targeting of pathogenic Treg cells without requiring direct identification of Treg-specific surface markers. This intermediary approach resolves the contradiction by providing both selectivity (through CD6high enrichment) and ease of operation (through commercially available anti-CD6 antibodies and standard flow cytometry).
Solution Approach 2:
The patent changes the parameter of cell surface CD6 expression levels to identify and target pathogenic Treg cells. By monitoring and manipulating CD6 expression levels (CD6high vs CD6low), the method enables selective targeting of activated, pathogenic Treg cells while sparing non-pathogenic populations. This parameter change approach allows effective immune modulation through controlled reduction of CD6high Treg cells using anti-CD6 antibodies, resolving the contradiction between selectivity and operational ease.
2Object-generated harmful factors
If anti-CD6 antibody is administered to reduce CD6high T cell levels, then pathogenic immune response is decreased, but monitoring and optimizing dosage requires precise measurement of CD6 levels
Solution Approach 1:
The patent implements a feedback mechanism where CD6 levels on T cells are measured (e.g., by flow cytometry) before and after anti-CD6 antibody administration. This feedback allows clinicians to monitor the reduction of CD6high pathogenic Treg cells and adjust subsequent dosing accordingly. The feedback loop ensures effective suppression of pathogenic immune responses while avoiding excessive immunosuppression, resolving the contradiction between reducing harm and achieving precise measurement through standardized immunological assays.
Solution Approach 2:
The patent replaces complex, specialized measurement systems with standard flow cytometry technology. By using commercially available anti-CD6 antibodies and conventional flow cytometry instruments, the method achieves precise measurement of CD6 levels without requiring novel or specialized equipment. This substitution resolves the contradiction by making precise measurement accessible through routine immunological techniques rather than requiring complex new systems.
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
Itolizumab effectively decreases cell surface CD6 levels on T-lymphocytes, reducing the Teff:Treg cell ratio and enhancing immune modulation, thereby ameliorating autoimmune and inflammatory diseases by maintaining CD6 levels within target ranges.
Implementation Method 1
In some embodiments, the methods comprise incubating the subject's cells with an anti-CD6 antibody that selectively strips, removes, or otherwise reduces cell surface CD6 from CD6high cells
Data Source
AI summary
Provided are methods and compositions comprising anti-CD6 antibodies, such as itolizumab, which selectively target CD6high T cells, for example, to reduce levels of cell surface CD6 on such cells, decrease the overall levels and pathogenic activity of CD6high T cells or the ratio of CD6high:CD6low T cells in a subject or ex vivo, decrease the overall levels and pathogenic activity of Teff cells or the ratio of Teff:Treg cells in a subject or ex vivo, and/or increase generation of Treg cells in a subject or ex vivo, and thereby modulate a pathogenic immune response in the subject, among other aspects.