TL1A-Binding Inhibitory Proteins for Selective Immune Signaling Blockade
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Solution Overview
Problem
Current technologies lack effective methods to inhibit or modulate the binding and signaling of TL1A to its receptors, DR3 and DcR3, which are involved in immune responses and inflammation.
Innovation Solution
Development of immunoreceptor inhibitory proteins (IIPs) that specifically bind to TL1A with high affinity, inhibiting its interaction with DR3 and DcR3, and modulating immune responses through these proteins or their conjugates, fusion proteins, and nucleic acid molecules.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Reliability
If TL1A binds to DR3 and DcR3, then immune response signaling is activated, but inflammation and harmful immune responses increase
Solution Approach 1:
The patent introduces immunoreceptor inhibitory proteins (IIPs) as intermediary molecules that bind to TL1A with high affinity, preventing TL1A from interacting with its receptors DR3 and DcR3. These IIPs act as mediators that block the harmful signaling pathway without interfering with other immune functions, thereby reducing inflammation while maintaining reliable immune response regulation.
2Object-generated harmful factors
If existing therapeutic approaches are used, then inflammation can be reduced, but specificity and effectiveness against TL1A signaling are insufficient
Solution Approach 1:
The patent designs IIPs with specific structural features (such as binding domains with particular amino acid sequences and affinities) that enable selective interaction with TL1A. This local quality optimization ensures that the therapeutic effect is highly specific to the TL1A-DR3/DcR3 pathway, avoiding off-target effects while maintaining reliable inhibition of the harmful signaling.
3Reliability
If high affinity binding to TL1A is achieved, then inhibition of TL1A-receptor interaction is improved, but protein design complexity increases
Solution Approach 1:
The patent divides the IIP into functional segments: a binding domain responsible for high-affinity TL1A interaction and other domains that may provide structural stability or functional modulation. This segmentation allows optimization of the binding interface without requiring the entire protein to be complex, thereby achieving high reliability binding while managing design complexity through modular architecture.
Data Source
AI summary
Provided herein are, inter alia, immunoreceptor inhibitory proteins and compositions (e.g., pharmaceutical compositions) comprising the same; as well as methods of making the immunoreceptor inhibitory proteins and compositions. The immunoreceptor inhibitory proteins provided herein are useful in e.g., pharmaceutical compositions and methods of use, including e.g., in the treatments of pro-inflammatory (e.g., autoimmune) diseases.