IL10R Binding Molecules for Selective Cell Activation
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Solution Overview
Problem
Current cytokine ligands often trigger adverse effects by activating both desired and undesired cell types, limiting their therapeutic potential due to off-target activity.
Innovation Solution
Development of cytokine receptor binding molecules comprising single domain antibodies that selectively bind to specific cytokine receptor subunits, facilitating targeted receptor dimerization and intracellular signaling without activating non-target cells.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Reliability
If cytokine ligands are used to activate desired cell types, then therapeutic effect is achieved, but off-target activation of undesired cell types occurs causing adverse effects
Solution Approach 1:
The cytokine ligand is divided into multiple separate binding domains, each specific to a particular receptor subunit. This segmentation allows independent optimization of binding specificity for each cell type marker, enabling precise control over which cell types are activated without unintended off-target effects
Solution Approach 2:
Different binding domains within the multimeric ligand are designed with different specificities for different receptor subunits expressed on different cell types. This local differentiation of binding properties enables the ligand to selectively activate only those cell types that express the specific combination of receptors required for multimer assembly
2Adaptability or versatility
If cytokine ligands activate multiple cell types, then broad immunomodulatory effect is achieved, but unwanted side effects increase
Solution Approach 1:
The ligand's binding parameters are engineered to require simultaneous binding to multiple specific receptor subunits. This changes the activation parameter from simple presence of a single receptor to a combinatorial requirement of multiple receptors, thereby maintaining broad immunomodulatory potential while eliminating activation of cell types that do not express the specific receptor combination
3Device complexity
If natural cytokine ligands are used, then simple structure is maintained, but ability to selectively target specific cell types is limited
Solution Approach 1:
The ligand is constructed as a composite multimeric structure combining multiple binding domains, each with specific affinity for different receptor subunits. This composite architecture achieves high manufacturing precision in terms of binding selectivity while maintaining relative structural simplicity through modular assembly of standardized domain units
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 cytokine receptor binding molecules achieve selective activation of desired cell types, minimizing unwanted side effects and enhancing the therapeutic efficacy of cytokine signaling.
Implementation Method 1
The binding molecule facilitates the dimerization of cytokine receptor subunits, bringing their intracellular domains into proximity such that intracellular signaling may occur
Data Source
AI summary
Provided herein are IL10R binding molecules that bind to IL10Ra and IL10Rb and comprise an IL10Rb sdAb and an IL10Rb VHH antibody.