Universal Immune Receptor for Multi-Antigen T Cell Targeting
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Solution Overview
Problem
Current CAR therapy for cancer is limited by its fixed antigen specificity, making it ineffective against heterogeneous tumors and prone to antigen loss variants, and it requires individual customization for each patient, which is technically and economically challenging.
Innovation Solution
Development of a universal immune receptor (UnivIR) comprising an extracellular label binding domain, a transmembrane domain, and a T cell receptor signaling domain, allowing T cells to target any antigen labeled with a specific label, such as biotin, enabling flexible antigen specificity and simultaneous or sequential targeting of multiple antigens.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Reliability
If CAR therapy uses fixed antigen specificity, then T cells can effectively target a single antigen, but the therapy becomes ineffective against heterogeneous tumors and antigen loss variants
Solution Approach 1:
The patent creates a universal immune receptor platform where a single T cell can recognize multiple different antigens through a common receptor structure that binds to various labeled antigens, enabling one T cell to perform multiple targeting functions rather than being limited to a single antigen specificity
Solution Approach 2:
The patent introduces dynamic antigen specificity by allowing the immune receptor to bind to different labeled antigens depending on what labels are present on tumor cells, making the targeting capability flexible and adaptable rather than fixed, enabling T cells to respond to heterogeneous tumor populations with varying antigen expressions
2Reliability
If CAR therapy is customized for each individual patient, then treatment specificity is improved, but the process becomes technically and economically challenging
Solution Approach 1:
The patent develops a universal immune receptor that can be applied across different patients and tumor types without requiring custom engineering for each case, maintaining treatment effectiveness through a standardized platform that works broadly rather than requiring individualized customization
Solution Approach 2:
The patent separates the targeting function from the T cell engineering by using external labels on antigens rather than encoding specificity within the T cell receptor itself, allowing the T cells to be standardized while the targeting labels can be adjusted to match different patient tumors
3Productivity
If CAR therapy targets a single antigen, then initial tumor regression is achieved, but antigen-loss variants are selected and tumor relapse occurs
Solution Approach 1:
The patent changes the parameter of antigen recognition from fixed specificity to flexible labeled-antigen binding, allowing the same T cell population to recognize multiple different antigens based on labeling, thereby preventing selection for antigen-loss variants that would escape single-antigen targeted therapy
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 UnivIR platform enables T cells to generate immune responses against diverse antigens, including tumors, by redirecting them to labeled antigens, potentially improving the efficacy and accessibility of CAR therapy by allowing broad antigen targeting and overcoming antigen loss variants.
Implementation Method 1
The UnivIR comprises an extracellular label binding domain, a transmembrane domain, a T cell receptor signaling domain, wherein the label binding domain binds to a labeled antigen
Data Source
AI summary
The invention provides compositions and methods for adoptive T cell therapy in treating a variety of disorders including cancer, infections, and autoimmune disorders. In one embodiment, the invention provides a universal immune receptor (UnivIR) that comprises an extracellular label binding domain, a transmembrane domain, and a cytoplasmic domain or otherwise an intracellular domain.