Chimeric Ligand Receptor for Targeted Immune Suppression
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Solution Overview
Problem
Current methods for suppressing undesired immune responses, such as in transplant rejections and autoimmune diseases, often result in general immune system suppression rather than targeted intervention, lacking specificity for specific antigens.
Innovation Solution
A fusion protein, referred to as a chimeric ligand receptor (CLR), is expressed in immune cells, comprising a ligand domain with epitopes of the cognate antigen, a spacer, a transmembrane domain, and an intracellular signaling domain, allowing for specific targeting and activation or elimination of immune cells reacting against these antigens.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Object-affected harmful factors
If general immune system suppression is used to treat undesired immune responses, then immune activity is reduced, but specificity for target antigens is lost
Solution Approach 1:
The patent applies local quality by designing a chimeric receptor that concentrates immune suppression function specifically at the site of antigen recognition. The receptor combines the antigen-binding specificity of a TCR with the suppressive signaling capability of a Treg cell, creating a localized suppressive effect only where the target antigen is present, rather than systemic suppression.
Solution Approach 2:
The invention uses composite materials by creating a chimeric receptor that fuses multiple functional domains: the TCR alpha and beta chains for antigen recognition, a Treg cell transmembrane domain for cellular localization, and the CTLA-4 intracellular signaling domain for suppressive function. This composite structure integrates specificity and suppression into a single molecular entity.
2Object-affected harmful factors
If CAR molecules are expressed in Treg cells for treatment of HvG disease, then suppressive activity is generated, but the approach is limited to specific transplant applications
Solution Approach 1:
The patent applies universality by designing a chimeric receptor platform that can be configured to target different antigens by simply changing the TCR variable regions, while maintaining the same suppressive signaling mechanism. This allows the same basic construct to be applied across different transplant scenarios and potentially other autoimmune conditions, making the approach universally applicable to various antigen-specific immune responses.
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 CLR enables selective inactivation or elimination of immune cells specific to the target antigen, thereby modulating immune responses without general immune suppression, effectively treating conditions like HvG disease, autoimmune diseases, and allergies.
Implementation Method 1
binding of a T-cell or B-cell or a NK cell to the ligand domain of the signalling molecule which is expressed by a CD4+ T-cell or a CD8+ T-cell results in activating the T-cell effector functions specifically against the T-cell or B-cell or NK cell that is bound to the ligand domain
Implementation Method 2
the signalling molecule contains at least one intracellular signalling domain... activating the T-cell effector functions specifically against the T-cell or B-cell or NK cell that is bound
Data Source
AI summary
A signalling molecule and an immune cell expressing the signalling molecule for use in the treatment of an undesired immune activity, which signalling molecule is a fusion protein which comprises a ligand domain, a spacer, a transmembrane domain, and at least one intracellular signalling domain, wherein the ligand domain comprises at least one epitope or all of the epitopes of the cognate antigen, or the cognate antigen, which cognate antigen is the target of the undesired immune activity.