Cytokine Receptor Pairing With sdAbs for Selective Cell Signaling
Find Innovative SolutionsGenerate Solutions
Solution Overview
Problem
The limited number of cytokine receptor pairings in nature restricts the scope of signaling-competent receptor pairs, leading to undesired effects when natural cytokines are used as therapeutics, and there is a need for targeted activation of specific cell types to treat diseases like cancer and infectious diseases.
Innovation Solution
Development of single-domain antibodies (sdAbs) that specifically bind to cytokine receptors, such as IL12Rβ1 and IL12Rβ2, IL27Rα, IL10Rα, IL10Rβ, IL10Rβ and IL28Rα, and IFNλR, to multimerize these receptors and trigger intracellular signaling, activating desired cell types like CD8+ T cells, CD4+ T cells, and macrophages.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Adaptability or versatility
If natural cytokines are used to activate cytokine receptors, then signaling is triggered, but the scope of receptor pairings is limited and undesired effects occur in non-target cells
Solution Approach 1:
The invention segments the cytokine molecule into separate binding domains, each specific to a particular receptor subtype. This allows independent targeting of different receptor pairs (e.g., IL-12Rβ1/β2 versus IL-23R/β2) using distinct binding domains within the same or separate molecules, thereby expanding the scope of receptor pairings while maintaining selectivity and reducing off-target effects.
Solution Approach 2:
The binding domains are engineered with localized specificity for different receptor subtypes. Each binding domain possesses unique structural characteristics that confer selective affinity for its target receptor, enabling spatially distinct binding events at different receptor locations on the cell surface, thus achieving targeted activation without cross-reactivity.
2Reliability
If natural cytokines are used therapeutically, then disease treatment is achieved, but adverse effects occur due to lack of cell-type specificity
Solution Approach 1:
By dividing the cytokine into separate binding domains with distinct receptor specificities, the invention enables selective delivery of therapeutic effects to specific cell types expressing particular receptor combinations. This segmentation allows the therapeutic agent to act only on intended targets (e.g., pathogenic T cells) while sparing other cell types, thereby maintaining reliability while reducing adverse effects.
Solution Approach 2:
The engineered binding domains serve as intermediaries between the therapeutic goal and the target cells. These domains mediate selective binding to specific receptor pairs on desired cell types, acting as a bridge that directs therapeutic activity precisely where needed while preventing unwanted interactions with non-target cells.
3Adaptability or versatility
If a ligand binds to multiple receptor subtypes, then broader signaling coverage is achieved, but selectivity for specific cell types is reduced
Solution Approach 1:
The invention resolves the conflict between breadth and precision by segmenting the ligand into multiple specialized binding domains. Each domain is tuned to recognize a specific receptor subtype with high precision, yet the combination of domains within a single molecule or therapeutic regimen achieves comprehensive signaling coverage across multiple cell types through coordinated action of the segmented components.
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 sdAbs enable selective activation of target cells, minimizing undesired signaling in non-target cells, providing therapeutic benefits in treating neoplastic diseases, inflammatory diseases, autoimmune diseases, and infectious diseases with reduced adverse effects.
Implementation Method 1
single-domain antibodies (sdAbs) that specifically bind to cytokine receptors, such as IL12Rβ1 and IL12Rβ2, IL27Rα, IL10Rα, IL10Rβ, IL10Rβ and IL28Rα, and IFNλR
Implementation Method 2
multimerize these receptors and trigger intracellular signaling
Data Source
AI summary
Provided herein are receptor binding proteins that bind to either natural cytokine receptor pairs or non-natural cytokine receptor pairs to create signaling diversity beyond natural receptor pairings.