Switchable Recombinant Polypeptide Receptors for Controlled Immune Modulation
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Solution Overview
Problem
Current cancer and autoimmune disease treatments using CAR T-cell therapy face challenges with specificity and adverse side effects such as cytokine storms, necessitating the development of more precise and controlled immune modulation systems.
Innovation Solution
A recombinant polypeptide system comprising artificial ligands and receptors, including nanobodies, that form switchable receptor complexes allowing for controlled signal transduction and immune modulation, reducing toxicity and adverse effects.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Reliability
If CAR T-cell therapy is used to treat cancer, then immune response against tumor targets is improved, but unspecific excessive immune activation and cytokine storms occur causing severe side effects
Solution Approach 1:
The invention divides the immune modulation function into separate modular components: artificial receptors with specific binding domains (e.g., nanobodies) and corresponding artificial ligands. This segmentation allows independent control of activation and inhibition signals, enabling precise regulation of T-cell responses without uncontrolled cytokine storms.
Solution Approach 2:
The patent introduces artificial ligands as intermediary molecules that mediate between the artificial receptor on T-cells and the desired immune response. These synthetic ligands (such as dimeric or multimeric constructs) provide controlled activation signals, replacing uncontrolled natural cytokine stimulation and preventing excessive immune activation.
2Ease of operation
If artificial ligands and receptors form switchable receptor complexes, then signal transduction control is improved, but system complexity increases
Solution Approach 1:
The invention creates dynamic, switchable receptor complexes that can transition between active and inactive states based on ligand binding. The artificial receptors are designed to form homo- or hetero-oligomeric complexes only upon binding specific artificial ligands, providing temporal and spatial control over signal transduction while maintaining relatively simple individual component structures.
Solution Approach 2:
The patent designs universal artificial receptor platforms that can recognize multiple different artificial ligands through modular binding domains. This multi-functionality allows a single receptor construct to participate in various signaling pathways by binding different ligands, reducing the need for numerous specialized components and simplifying the overall system architecture.
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 system enables precise immune modulation with reduced toxicity and adverse effects, allowing for enhanced proliferation of tumor-reactive T-cells and improved therapeutic outcomes in cancer and autoimmune diseases.
Implementation Method 1
a first binding partner of a binding pair selected from an artificial ligand and a receptor binding the artificial ligand
Data Source
AI summary
In a first aspect, the present invention relates to new recombinant artificial polypeptides allowing cytoplasmic signaling in cells containing the same. In particular, the present invention relates to a system for transmitting signals containing a recombinant polypeptide containing a domain with a first binding partner selected from an artificial ligand and a receptor binding an artificial ligand, a transmembrane domain and a cytoplasmic signaling domain whereby the domain with the binding partner and the cytoplasmic signaling domain are a combination of domains not naturally occurring in an organism and the second binding partner for specific forming of the binding pair. In a further aspect, a nucleic acid molecule comprising a nucleic acid sequence encoding the polypeptide according to the present invention as well as a vector, cell, cell line or host cell containing said vector are provided. In addition, the present invention relates to the use of the recombinant polypeptide according to the present invention in treating cancer or autoimmune disease or allowing immune modulation of a subject as well as for use to change the status of cells when applying the specific second binding partner of the first binding partner present in the recombinant polypeptide according to the present invention.