Hinge-Modulated Engineered Immune Cells for Targeted Cytotoxicity
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Solution Overview
Problem
Existing engineered immune cells, such as CAR and TCR cells, face inefficacy in vivo and severe side effects, limiting their therapeutic use due to lack of targeted cytotoxic responses and non-specific activation.
Innovation Solution
Engineered immune cells with modular activating and blocking receptors that form micro-clusters, allowing localized cytotoxic responses on target cells while minimizing effects on non-target cells, through reversible receptor expression and cross-talk modulation.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Reliability
If engineered immune cells express activating receptors to kill target cells, then cytotoxic efficacy is improved, but non-specific activation against non-target cells causes severe side effects
Solution Approach 1:
The patent applies local quality by creating spatially distinct micro-clusters on the immune cell surface: activating receptors cluster near target cells to enable cytotoxicity, while blocking receptors cluster near non-target cells to prevent activation. This localized receptor distribution allows the same immune cell to exhibit different functional qualities in different spatial contexts, resolving the contradiction between efficacy and safety.
Solution Approach 2:
The patent implements dynamics through reversible receptor expression modulation. Blocking receptors dynamically reduce activating receptor surface expression in response to non-target cell contact, and this reduction is reversible when target cells are encountered. This dynamic adaptation allows the immune cell to switch between active and inhibited states based on the target type, maintaining both cytotoxic efficacy and reduced side effects.
2Reliability
If activating receptors are continuously expressed to ensure target cell recognition, then therapeutic efficacy is improved, but chronic activation leads to immune cell exhaustion and death
Solution Approach 1:
The patent applies periodic action through reversible modulation of activating receptor expression. Instead of continuous expression, the activating receptors are periodically upregulated when target cells are present and downregulated when non-target cells are present or during circulation. This periodic expression pattern prevents chronic activation while maintaining therapeutic efficacy, thereby extending immune cell persistence and reducing exhaustion.
3Object-affected harmful factors
If blocking receptors are added to prevent non-target cell activation, then safety profile is improved, but receptor signal interference may reduce cytotoxic response against target cells
Solution Approach 1:
The patent applies copying by creating distinct, non-overlapping signaling micro-clusters for activating and blocking receptors. Each receptor type operates in its own spatial copy or zone on the immune cell surface, preventing signal interference while maintaining both functions. The blocking receptor cluster copies the organizational structure of the activating cluster but maintains functional independence through spatial separation and reversible expression control.
Data Source
AI summary
The present disclosure provides engineered immune cells and methods for their creation and use. The immune cells comprise activating and blocking receptors, that exhibit cross-talk between the receptors.