LTα-Deficient Regulatory T Cells for Autoimmune Therapy
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Solution Overview
Problem
Current Treg cell therapy for autoimmune and inflammatory disorders requires a large number of cells for effective treatment, and there is a need to develop new therapies that can reduce the required cell numbers while maintaining immunosuppressive activity.
Innovation Solution
The development of regulatory T cells that do not express or express reduced levels of lymphotoxin alpha (LTα), which are genetically modified to silence the LTα gene, thereby increasing their suppressive activity and allowing for a reduction in the number of cells needed for therapy.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Quantity of substance
If conventional Treg cells are used for therapy, then immunosuppressive activity is provided, but a large number of cells are required for effective treatment
Solution Approach 1:
The patent applies parameter changes by genetically modifying Treg cells to alter their lymphotoxin alpha (LTα) expression levels. By reducing or eliminating LTα expression through gene silencing techniques, the Treg cells exhibit enhanced immunosuppressive activity per cell, thereby reducing the total number of cells needed for effective therapy while maintaining or improving therapeutic reliability
2Quantity of substance
If the number of Treg cells is reduced for therapy, then cell dosage is lowered, but immunosuppressive efficacy may be compromised
Solution Approach 1:
The patent resolves this contradiction by changing the functional parameters of Treg cells through genetic modification. By silencing the LTα gene, each cell becomes more potent in its immunosuppressive function, allowing reduced cell dosage while maintaining therapeutic efficacy. The enhanced per-cell activity compensates for the lower total cell number
Solution Approach 2:
The patent applies the extraction principle by removing or reducing the expression of lymphotoxin alpha, a molecule that limits Treg suppressive activity. By taking out this inhibitory factor through gene silencing, the remaining Treg cells achieve higher immunosuppressive potency, enabling effective therapy with fewer cells
Data Source
AI summary
The present invention relates to regulatory T cell and uses thereof. By their immunosuppressive and anti-inflammatory activities, regulatory T cells play a central role in peripheral tolerance and thus critically prevent the development of autoimmune and inflammatory disorders. The inventors showed that Foxp3+CD4+ Tregs express high levels of LTα, which negatively regulates their immunosuppressive signature. They demonstrated that the adoptive transfer of LTα−/− Tregs in mice protects from dextran sodium sulfate (DSS)-induced colitis and attenuates inflammatory bowel disease (IBD), multi-organ autoimmunity and the development of CAC. The inventors also showed that by mixed bone marrow chimeras that LTα expression specifically in hematopoietic cells negatively controls the immunosuppressive signature of Tregs. In particular, the present invention relates to regulatory T cell characterized in that it does not express or expresses reduced levels of lymphotoxin alpha.