IL-37-Expressing CD4+ T Cells for Stable FOXP3 Maintenance
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Solution Overview
Problem
Current immunotherapies using adoptive transfer of Treg cells face instability, leading to loss of FOXP3 expression and conversion to inflammatory T cells, exacerbating immune diseases.
Innovation Solution
Production of modified CD4+ T cells expressing high levels of IL-37 to stabilize Treg cells and induce a Treg-like phenotype, using methods that introduce IL-37 or its encoding nucleic acid sequences under suitable conditions.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Reliability
If Treg cells are used for adoptive transfer therapy, then immunosuppressive function is provided, but the cells are unstable and convert to inflammatory T cells
Solution Approach 1:
The patent changes the expression level parameter of IL-37 in Treg cells from endogenous to high levels (10-1000 fold increase), which stabilizes FOXP3 expression and prevents conversion to inflammatory T cells. This parameter change directly addresses the instability issue while maintaining immunosuppressive function.
Solution Approach 2:
The patent performs preliminary genetic modification to introduce IL-37 expression constructs into Treg cells before adoptive transfer. This preliminary action ensures that the cells are pre-stabilized with high IL-37 expression, preventing subsequent conversion to inflammatory phenotypes during therapy.
2Reliability
If FOXP3 expression is maintained in Treg cells, then immunosuppressive function is preserved, but under inflammatory conditions FOXP3 is lost and suppressive function fails
Solution Approach 1:
The patent applies preliminary anti-action by introducing high levels of IL-37 expression before inflammatory challenges occur. IL-37 acts as a protective factor that counteracts the inflammatory-induced loss of FOXP3, thereby maintaining suppressive function even under inflammatory conditions.
Solution Approach 2:
The patent changes the concentration parameter of IL-37 from physiological levels to pharmacologically high levels (10-1000 fold increase), which creates a protective threshold that prevents FOXP3 loss even when exposed to inflammatory cytokines and stimuli.
3Productivity
If conventional Treg cell therapy is used, then treatment of immune diseases is attempted, but therapeutic failure occurs due to Treg cell dysfunction
Solution Approach 1:
The patent creates a composite cellular product by combining Treg cells with exogenous IL-37 expression constructs. This composite approach integrates the immunosuppressive properties of Treg cells with the stabilizing effects of high IL-37 expression, resulting in a therapeutically superior cell product with enhanced reliability and efficacy.
Data Source
AI summary
Disclosed herein are methods of producing a population of modified CD4+T cells expressing nuclear IL-37. Also disclosed are methods of using the modified CD4+T cells expressing nuclear IL-37 for the treatment of immune or inflammatory diseases, disorders, or conditions.