Dual-Domain Chimeric Proteins for Autoimmune Immune Modulation
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Solution Overview
Problem
Current treatments for autoimmune diseases like inflammatory bowel disease and irritable bowel syndrome are inadequate, lacking effective therapies that minimize infection risk while modulating immune responses.
Innovation Solution
Development of chimeric proteins comprising two domains that bind to specific ligands/receptors, activating immune inhibitory signals or inhibiting immune activating signals, thereby reducing self-directed immune system activity.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Reliability
If current treatments for autoimmune diseases are used, then immune response is modulated, but infection risk increases
Solution Approach 1:
The chimeric protein is divided into two distinct functional domains: a first domain that binds to an activating ligand/receptor to inhibit immune activation, and a second domain that binds to an inhibitory ligand/receptor to enhance immune suppression. This segmentation allows each domain to independently perform its specific function, achieving effective immune modulation while controlling infection risk through balanced dual-action mechanisms.
2Reliability
If chimeric proteins with dual domains are developed, then immune modulation effectiveness improves, but protein structure complexity increases
Solution Approach 1:
Two separate functional domains are merged into a single chimeric protein molecule through a linker sequence. The first domain (inhibiting immune activation) and the second domain (enhancing immune suppression) are covalently connected, allowing the protein to exert dual immunomodulatory effects simultaneously. This merging approach maintains structural integrity while achieving coordinated immune regulation.
Solution Approach 2:
The chimeric protein is designed with multi-functionality, where a single molecule performs multiple immunomodulatory functions: blocking activating ligand-receptor interactions, enhancing inhibitory ligand-receptor interactions, and regulating immune responses through multiple pathways. This universal design improves therapeutic effectiveness while reducing the need for multiple separate agents.
3Ease of operation
If single-domain immunotherapies are used, then treatment is simple, but efficacy in non-responsive or resistant patients is insufficient
Solution Approach 1:
The chimeric protein provides dynamic immune regulation by simultaneously engaging both activating and inhibitory ligand-receptor pathways. This dynamic dual-action mechanism allows the therapy to adapt to varying immune states, making it effective for non-responsive or resistant patients who may not respond to static single-domain therapies. The balanced inhibition and enhancement create a more resilient therapeutic effect.
Data Source
AI summary
The present disclosure relates, inter alia, to compositions and methods, including chimeric proteins, and nucleic acids encoding the chimeric proteins having a first domain comprising an extracellular domain of a first transmembrane protein, a first secreted protein, or a first membrane-anchored extracellular protein and a second domain comprising an extracellular domain of a second transmembrane protein, a second secreted protein, or a second membrane-anchored extracellular protein, in which either or both of the first domain and the second domain decreases self-directed immune system activity when bound to its ligand/receptor. Accordingly, the present disclosure find use in the treatment of autoimmune diseases, and particularly, inflammatory bowel diseases.