Recombinant Molecule Inhibiting IL-23 Signaling
Find Innovative SolutionsGenerate Solutions
Solution Overview
Problem
Current treatments for cancer and inflammatory disorders often activate IL-23-dependent immune cells, leading to suppressed antitumor immunity and immune-related adverse events, as existing therapies fail to effectively modulate IL-23 signaling.
Innovation Solution
Development of a recombinant molecule comprising an IL-23 inhibiting polypeptide that binds to IL-23 or IL-23R, combined with a target binding polypeptide that interacts with immune checkpoint proteins or immune stimulatory receptors, to inhibit IL-23 signaling and enhance antitumor immune responses.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Reliability
If existing therapies are used to treat cancer and inflammatory disorders, then immune activation occurs, but IL-23-dependent immune cells are activated leading to suppressed antitumor immunity and immune-related adverse events
Solution Approach 1:
The invention segments the immune modulation function by specifically targeting IL-23 signaling pathway components (IL-23p19 subunit or IL-23R) rather than broadly activating all immune cells. This selective segmentation allows therapeutic effect while avoiding harmful activation of IL-23-dependent cells that cause adverse events
Solution Approach 2:
The patent uses engineered proteins (anti-IL-23p19 antibodies or anti-IL-23R antibodies) as intermediary molecules that specifically bind to and modulate IL-23 signaling. These intermediaries enable precise control of immune activation, blocking harmful IL-23-dependent pathways while preserving beneficial immune responses
2Reliability
If immune checkpoint inhibitors are used to enhance antitumor immunity, then immune activation increases, but IL-23 signaling promotes inflammatory mediators that suppress antitumor immunity
Solution Approach 1:
The invention applies preliminary anti-action by pre-blockade of IL-23 signaling before or during immune checkpoint inhibition therapy. By预先 blocking the IL-23 pathway that promotes tumor-supportive inflammation, the therapy prevents the development of harmful inflammatory responses while maintaining antitumor immunity enhancement
3Productivity
If broad immune activation is used to treat cancer, then antitumor response increases, but immune-related adverse events increase
Solution Approach 1:
The patent applies local quality by directing immune modulation specifically at the IL-23 signaling pathway nodes (IL-23p19 or IL-23R) rather than globally affecting all immune pathways. This localized approach enables selective suppression of harmful IL-23-dependent inflammation while preserving other beneficial immune responses, achieving better therapeutic index
Data Source
AI summary
The present disclosure provides recombinant molecules, compositions and methods for modulating the IL-23 axis. In certain embodiments, these recombinant molecules are used in methods of treating and/or preventing treatment of cancer, autoimmune diseases, and inflammatory disorders associated with the IL-23 axis and signaling.