Regulatory T Cell Therapy via Lymphotoxin Alpha Blocking
Find Innovative SolutionsGenerate Solutions
Solution Overview
Problem
Current Treg cell therapy for autoimmune and inflammatory disorders requires a large quantity of cells, making it inefficient and costly.
Innovation Solution
Incubating regulatory T cells with a lymphotoxin alpha blocking agent, such as a soluble lymphotoxin-β receptor (LTβR), to enhance their suppressive activity, thereby reducing the required cell numbers for effective therapy.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Reliability
If a large quantity of Treg cells is used for therapy, then effective treatment of autoimmune and inflammatory disorders is achieved, but the cost and complexity of the therapy increases
Solution Approach 1:
The patent changes the functional parameter of Treg cells by blocking the LTα-LTβR interaction pathway. This parameter change enhances the suppressive activity of each individual Treg cell, allowing therapeutic effectiveness to be achieved with a lower quantity of cells. The blocking agent modifies the biological activity parameter of Treg cells without changing their physical quantity.
Solution Approach 2:
The patent introduces a lymphotoxin alpha blocking agent as an intermediary substance that mediates between the Treg cells and the inflammatory environment. This blocking agent potentiates the suppressive function of Treg cells by interfering with the LTα-LTβR signaling pathway, thereby amplifying the therapeutic effect per cell.
2Productivity
If the number of Treg cells is reduced for cost-effective therapy, then treatment efficiency improves, but therapeutic effectiveness may be compromised
Solution Approach 1:
The patent applies parameter changes by modifying the functional state of Treg cells through LTα blocking. This changes the suppressive activity parameter, allowing fewer cells to achieve the same therapeutic effect. The functional parameter enhancement compensates for the reduced cell quantity, maintaining effectiveness while improving efficiency.
Solution Approach 2:
The patent applies preliminary action by pre-treating Treg cells with the LTα blocking agent before administration. This preliminary modification enhances the suppressive capacity of the cells in advance, ensuring that even a reduced number of cells will be sufficiently potent to achieve therapeutic effectiveness when introduced into the patient.
3Ease of manufacture
If conventional Treg cell therapy is used without blocking agents, then the therapy process is simpler, but the required cell quantity and cost increase
Solution Approach 1:
The patent introduces a blocking agent as an intermediary that can be incorporated into the Treg cell preparation process. While this adds a step to the manufacturing process, it dramatically reduces the final cell quantity required, thereby improving overall cost-effectiveness despite the increased procedural complexity.
Solution Approach 2:
The patent modifies the functional parameters of Treg cells through the blocking agent during preparation. This parameter change occurs during the manufacturing process, enhancing cell potency before administration. The added manufacturing step is offset by the reduced cell quantity needed, improving the overall efficiency of the therapy.
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
The enhanced suppressive activity of Tregs allows for effective treatment of autoimmune and inflammatory disorders with a significantly lower number of cells, improving the efficiency and cost-effectiveness of Treg cell therapy.
Implementation Method 1
LTα1β2/LTβR interactions between Tregs and antigen presenting cells (i.e. dendritic cells and thymic epithelial cells) respectively control the immunosuppressive signature of Tregs
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. The inventors have demonstrated that the adoptive transfer of Tregs previously incubated with soluble lymphotoxin-β receptor in mice protects from dextran sodium sulfate (DSS)-induced colitis. Thus, the number of cells to be injected in adoptive transfer may be reduced and a transfection or transduction step avoided, which represents a technical facilitation. In particular, the present invention relates to a method of treating or preventing autoimmune disorders and inflammatory-associated cancers in a subject in need thereof comprising the step of administrating to the subject a therapeutically effective amount of regulatory T cells which have been previously incubated with effective amount of soluble lymphotoxin-β receptor.