Peptide Targeting Modules for Stable Universal CAR Cell Targeting
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Solution Overview
Problem
Conventional chimeric antigen receptor (CAR) technology for immune cells faces challenges such as immunogenicity of exogenous tags, complex production processes, and limited stability, leading to safety issues and inefficiencies in targeting multiple antigens.
Innovation Solution
Development of chemically synthesized peptide binding moieties specific for human cell surface proteins, derived from non-immunogenic human nuclear proteins, which are easily manufactured and stable, allowing for rapid and economic production of targeting modules that bind to universal chimeric antigen receptors (UniCARs) to target cellular surface proteins.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Adaptability or versatility
If multiple different immune cell types are used to express different CARs, then the ability to treat various diseases is improved, but the complexity of manufacturing and regulating multiple cell therapies increases
Solution Approach 1:
The patent creates a universal immune cell platform that can express multiple different CARs simultaneously. The modified immune cells are engineered to accept and express heterologous CARs with different specificities, allowing a single cell product to target multiple antigens and treat various diseases including cancer, infections, and autoimmune disorders, thereby eliminating the need for separate manufacturing processes for each disease indication.
Solution Approach 2:
The patent segments the CAR structure into modular components that can be independently designed and combined. The CAR construct includes separate domains for antigen recognition, co-stimulation, and cytotoxicity, which can be configured in different combinations to create CARs with different specificities that can all be expressed in the same immune cell population.
2Device complexity
If a single immune cell type is used to express multiple CARs, then manufacturing complexity is reduced, but the risk of off-target effects and autoimmune disorders increases
Solution Approach 1:
The patent implements local quality control by providing different levels of co-stimulatory signals to different CAR-expressing cell populations. The immune cells can be configured with specific co-stimulation domains that are tailored to their intended target, allowing precise control over activation thresholds and reducing the risk of off-target effects while maintaining manufacturing simplicity.
Solution Approach 2:
The patent incorporates feedback mechanisms through selectable markers and kill switches that allow real-time monitoring and control of CAR-expressing immune cells. These safety features enable the system to respond to unexpected activation or off-target effects by selectively eliminating problematic cell populations, thereby reducing autoimmune risks while maintaining a unified manufacturing approach.
Data Source
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AI summary
The present invention relates to a targeting module comprising a chemically synthesized peptide binding moiety specific for a human cell surface protein or protein complex, a kit comprising the targeting module and a vector or a cell comprising a nucleic acid encoding a universal chimeric antigen receptor and the use for the treatment of cancer, infections and autoimmune disorders.