Programmable Immunocyte Receptor Complex for Antigen Specificity
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Solution Overview
Problem
Current CAR T cell systems face challenges such as the need for separate cell development paths for each target antigen, unregulated persistence leading to cytokine release syndrome, limited applicability beyond cancer treatment, and issues with tumor heterogeneity and off-target effects.
Innovation Solution
The development of a programmable immunocyte receptor complex system that includes modified cell receptor complexes with biotin-binding components or FcγRI receptor components, allowing for the use of universal target detector molecules to redirect the specificity of immunocytes, thereby overcoming the limitations of existing CAR T cell systems.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Measurement precision
If separate cell development paths are used for each target antigen, then specificity to target antigen is improved, but device complexity and manufacturing time increase
Solution Approach 1:
The patent applies universality by creating a universal immunocyte platform that can recognize multiple target antigens through a single receptor complex design. The modified T cell receptor complex with biotin-binding components can bind to various biotinylated target detector molecules, allowing one cell type to target multiple antigens without requiring separate development paths for each target, thus reducing complexity while maintaining specificity
Solution Approach 2:
The patent uses an intermediary approach by introducing biotin-binding components as a mediator between the immunocyte receptor and target detector molecules. This intermediary mechanism allows the same receptor complex to interact with different biotinylated targets through the common biotin-biotin-binding interface, enabling multi-target capability without requiring multiple specialized cell development paths
2Duration of action of stationary object
If CAR T cells are engineered to persist long-term, then therapeutic effectiveness is improved, but harmful factors increase due to cytokine release syndrome
Solution Approach 1:
The patent applies dynamics by making the immunocyte activity regulatable rather than static. The modified receptor complex allows for dynamic control of cell activation and cytokine release through the binding of target detector molecules. This enables the system to adapt its activity level - maintaining persistence for therapeutic effect while allowing modulation to reduce harmful cytokine release when appropriate
Solution Approach 2:
The patent implements feedback control through the target-detector mediated activation mechanism. The immunocytes are activated in response to target detection, and this same mechanism allows for feedback regulation where the presence or absence of target detector molecules can modulate the level of cell activation and cytokine release, enabling long-term persistence with controlled harmful effects
3Stability of the object's composition
If viral vectors are used to integrate transgenes into host cell genome, then transgene expression stability is improved, but harmful factors increase due to genotoxicity
Solution Approach 1:
The patent applies the extraction principle by removing the harmful integrating viral vector component from the system. Instead of using viral vectors that integrate into the genome, the invention uses non-integrating delivery methods for the modified T cell receptor complex, thereby extracting the genotoxicity element while preserving the ability to achieve stable transgene expression through alternative mechanisms
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
This system enables rapid adaptability to different targets, modulates cell activity for safety, enhances signaling capacity and persistence, and reduces off-target effects, making it a more predictable and effective approach for both cancer and infectious disease treatments.
Implementation Method 1
at least one of the plurality of receptor subunits has been engineered or modified to include either: (i) a biotin-binding component that binds to a biotinylated target detector molecule
Implementation Method 2
an FcγRI receptor component that binds to a target detector molecule that is separate from the receptor complex
Implementation Method 3
Inside the CAR T cells, these antigen-recognition domains are linked to the CD3ζ-chain for intracellular signaling. Upon binding of a specific antigen by the surface receptor, the signaling domain activates cytokine release, target cell lysis and T-cell proliferation.
Data Source
AI summary
A programmable cell receptor complex expressed by an immunocyte, wherein the programmable receptor complex includes a plurality modified receptor subunits, wherein the modified receptor subunits have been engineered or modified to include FcγRI receptor components, biotin-binding components, or both, and wherein the FcγRI receptor components and biotin-binding components are operative to bind to target detector molecules that bind to or otherwise interact with predetermined targets.