Switchable CAR-EC T Cell Therapy Control via Peptide Neo-Epitope
Find Innovative SolutionsGenerate Solutions
Solution Overview
Problem
Current chimeric antigen receptor T cell (CAR T-cell) therapies lack control over CAR T-cell activity, leading to unreliable treatments due to constant activation, which can result in adverse effects such as cytokine release syndrome and tumor lysis syndrome, and require empirical design for each target antigen, limiting flexibility and safety.
Innovation Solution
Development of switchable chimeric antigen receptor effector cells (CAR-ECs) with CAR-EC switches that comprise a peptide neo-epitope binding to a chimeric antigen receptor and a targeting moiety binding to a cell surface molecule, allowing for controlled activation and deactivation, titration of responses, and redirection to multiple therapeutic targets.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Reliability
If CAR T-cell therapies are designed to constantly activate T cells to eliminate tumor cells, then the effectiveness against malignant cells is improved, but adverse effects such as cytokine release syndrome and tumor lysis syndrome increase
Solution Approach 1:
The patent introduces a switchable CAR system where the CAR construct includes a controllable activation domain. The T cell activation state can be dynamically adjusted from constantly active to controllable/switchable, allowing the system to adapt between therapeutic effectiveness and safety based on treatment phase and patient response.
Solution Approach 2:
The patent introduces a molecular switch (e.g., drug-binding domain or inducible promoter system) as an intermediary between the CAR and T cell activation machinery. This intermediary allows external control (via administered drugs or other molecules) to modulate T cell activation, providing a safety mechanism to reduce adverse effects while maintaining therapeutic effectiveness.
2Adaptability or versatility
If switchable CAR-EC systems are introduced to enable controlled activation and deactivation, then safety and flexibility are improved, but device complexity increases
Solution Approach 1:
The patent divides the CAR construct into modular functional domains: an extracellular antigen-binding domain, a hinge region, a transmembrane domain, and a controllable intracellular signaling domain. This segmentation allows independent optimization of each module and simplifies the design of switchable mechanisms by treating them as separate functional components that can be assembled systematically.
Solution Approach 2:
The patent designs the switchable CAR system using universal control mechanisms (e.g., common drug-binding domains or inducible promoters) that can be applied across different CAR constructs targeting various antigens. This universality reduces overall system complexity by providing a standardized switchable framework that can be reused across multiple therapeutic applications.
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 switchable CAR-EC system provides safer, more versatile immunotherapies by enabling controlled activation and deactivation, reducing adverse effects, and allowing for targeted therapy with increased flexibility and safety, promoting long-lived memory cells and optimized immunological synapses.
Implementation Method 1
A first cysteine of a first chimeric antigen receptor and a second cysteine of a second chimeric antigen receptor may form a disulfide bond, resulting in multimerization of the first chimeric antigen receptor and the second chimeric antigen receptor.
Data Source
AI summary
Disclosed herein are chimeric antigen receptor effector cells (CAR-ECs) and CAR-EC switches. The switchable CAR-ECs are generally T cells. The one or more chimeric antigen receptors may recognize a peptidic antigen on the CAR-EC switch. The CAR-ECs and switches may be used for the treatment of a condition in a subject in need thereof.