IL10Rα/IL2Rγ Binding Protein Selective Receptor Pairing
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Solution Overview
Problem
The existing use of IL10 as a therapeutic agent can trigger both immunosuppressive and immunostimulatory effects on various cell types, leading to adverse and undesirable effects due to the presence of IL10R on different cell types.
Innovation Solution
Development of an IL10Rα/IL2Rγ binding protein comprising an anti-IL10Rα VHH antibody and an anti-IL2Rγ VHH antibody, which specifically binds to IL10Rα and IL2Rγ, allowing for selective activation of desired cell types while minimizing activation of other cell types.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Reliability
If IL10 is used as a therapeutic agent, then immunosuppressive effects are achieved, but immunostimulatory effects and adverse side effects occur due to IL10R presence on multiple cell types
Solution Approach 1:
The invention segments the IL10R receptor complex into two distinct subunits (IL10Rα and IL10Rβ) and develops separate binding proteins that can selectively target each subunit. This allows independent control of immunosuppressive and immunostimulatory pathways, enabling therapeutic effects while avoiding adverse effects associated with broad IL10R activation.
Solution Approach 2:
The binding proteins are designed with specific binding affinities for either IL10Rα or IL10Rβ subunits, creating local specificity within the receptor complex. This enables selective modulation of signaling pathways in specific cell types, achieving desired therapeutic effects while minimizing off-target adverse effects.
2Adaptability or versatility
If IL10 binds to IL10R on various cell types, then broad immunomodulatory effects are achieved, but selectivity and precision of therapeutic action are reduced
Solution Approach 1:
The invention divides the broad IL10R signaling into separate α and β subunit pathways, allowing development of binding proteins with selective affinity for each subunit. This segmentation enables precise targeting of specific cell types expressing particular subunit combinations while maintaining broad adaptability through selective pathway activation.
Solution Approach 2:
The binding proteins exhibit different binding affinity parameters for IL10Rα versus IL10Rβ subunits. By adjusting these affinity parameters, the invention achieves selective activation of desired cell types with high precision while maintaining the ability to modulate immune responses across multiple cell types through appropriate protein selection.
Data Source
AI summary
Provided herein are IL10Rα/IL2Rγ binding proteins that bind to IL10Rα and IL2Rγ and comprise an anti-IL10Rα VHH antibody and an anti-IL2Rγ VHH antibody.