IL-7Rα Ligand Peptides for Targeted Immune Modulation
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Solution Overview
Problem
Current therapies for cancer, autoimmune diseases, and inflammatory diseases often lack effective targeting of the IL-7/IL-7R pathway, which is crucial for immune responses and tumor control, with recombinant IL-7 administration showing promise but needing more specific and potent IL-7R agonists.
Innovation Solution
Development of IL-7Rα ligands with specific amino acid sequences that bind to the human IL-7Rα subunit with high affinity, providing therapeutic options for treating cancer, autoimmune diseases, and inflammatory diseases by modulating IL-7R signaling.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Reliability
If recombinant IL-7 is administered to increase T cell proliferation and immune responses, then therapeutic efficacy is improved, but specificity and potency in targeting IL-7Rα are insufficient
Solution Approach 1:
The patent extracts the specific IL-7Rα binding domain from the full IL-7 cytokine structure. The disclosed peptides (e.g., SEQ ID NOS: 1-10) represent isolated binding epitopes that specifically target IL-7Rα without requiring the complete IL-7 molecule, thereby achieving targeted therapy with improved specificity while maintaining therapeutic efficacy.
Solution Approach 2:
The invention applies local quality by designing peptides with specific amino acid sequences that bind to particular regions of the IL-7Rα receptor. The peptides are engineered to interact with specific epitopes on IL-7Rα (such as the WSXWS motif region), providing localized and selective binding that enhances specificity while preserving the ability to modulate IL-7R signaling pathways.
2Reliability
If IL-7Rα ligands are designed to bind with high affinity (IC50 < 100 μM), then potency is improved, but complexity of peptide sequence design increases
Solution Approach 1:
The patent employs parameter changes by systematically varying amino acid sequences to optimize binding affinity. Specific amino acid substitutions, additions, and deletions are made to the core peptide sequences (e.g., modifying SEQ ID NOS: 1-10) to enhance binding to IL-7Rα while maintaining manageable sequence complexity. The invention identifies key residue positions that critically affect affinity, allowing focused optimization without exhaustive sequence exploration.
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 IL-7Rα ligands offer a potent and specific mechanism to modulate IL-7R signaling, potentially enhancing antitumor effects, improving immune responses, and treating various diseases by administering them as pharmaceutical compositions or nucleic acids encoding these ligands.
Implementation Method 1
IL-7Rα ligands are disclosed that bind to the human IL-7Rα subunit with an IC50 of less than 100 μM
Data Source
AI summary
IL-7Rα ligands and compounds comprising IL-7Rα ligands are disclosed. The IL-7Rα binding compounds include fusion proteins comprising the IL-7Rα ligands and can act as IL-7R agonists.