PEbody CAR Immune Cells for Switchable Antigen Targeting
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Solution Overview
Problem
Existing CAR T cell therapies face challenges in efficiently targeting diverse cancer antigens due to antigen loss and the need for re-engineering immune cells to switch targets, limiting their versatility in treating different cancer types.
Innovation Solution
A two-component receptor system, the PEbody CAR, comprising a R-Phycoerythrin-targeting receptor (PEbody) expressed on immune effector cells and PE-conjugated antibodies, allows for targeting different antigens without re-engineering, using a synthetic binding protein derived from human fibronectin as a molecular scaffold.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Reliability
If conventional CAR T cell therapy is used to target specific cancer antigens, then cancer cells can be destroyed effectively, but antigen loss occurs and re-engineering is needed to switch targets
Solution Approach 1:
The CAR T cell system is segmented into two independent components: (1) a universal PEbody CAR T cell that recognizes PE-conjugated antibodies, and (2) different PE-conjugated antibodies targeting specific cancer antigens. This segmentation allows the T cell to remain unchanged while the target specificity is switched by changing the PE-conjugated antibody component.
Solution Approach 2:
PE-conjugated antibodies serve as intermediary molecules that bridge the universal PEbody CAR T cell and the diverse cancer antigens. The PEbody on the T cell binds to the PE-conjugated antibody, which in turn binds to the cancer antigen, enabling the T cell to target different cancers without re-engineering.
2Adaptability or versatility
If immune cells are re-engineered to target different cancer antigens, then new cancer types can be treated, but the complexity and time required for treatment increases
Solution Approach 1:
The PEbody CAR T cell is designed as a universal platform that can recognize multiple different cancer antigens through PE-conjugated antibodies. A single PEbody CAR T cell product can be used to treat various cancer types by simply changing the PE-conjugated antibody, eliminating the need for repeated re-engineering processes.
Solution Approach 2:
The PEbody is pre-engineered into the CAR T cell during manufacturing, creating a universal platform in advance. This preliminary action enables rapid switching between different cancer targets by only changing the PE-conjugated antibody, rather than re-engineering the entire CAR T cell for each new target.
3Measurement precision
If conventional CAR T cell therapy is used, then specific cancer antigens can be targeted, but the system lacks flexibility for treating diverse cancer types
Solution Approach 1:
The system transitions from a static, fixed-target CAR T cell to a dynamic, switchable-target system. The PEbody CAR T cell maintains stable recognition of PE-conjugated antibodies while the specific target can be dynamically changed by introducing different PE-conjugated antibodies, providing both precision and flexibility.
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
Enables immune effector cells to selectively target and destroy various cancer cells and viral-infected cells by switching PE-conjugated antibodies, overcoming antigen loss and enhancing therapeutic flexibility.
Implementation Method 1
the PEbody and the PE-conjugated antibody are capable of specifically binding to each other
Data Source
AI summary
In alternative embodiments, provided are compositions, including products of manufacture and kits, and methods, for engineering immune effector cells, e.g., T cells, NK cells, monocytes and/or macrophages to recognize and destroy a desired target cell, which can be a cancer cell, a dysfunctional cell, or an infected cell.