UniCAR System Modular Retargeting for Immune Safety
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Solution Overview
Problem
Conventional CAR technology faces safety issues due to uncontrolled immune responses and limited antigen specificity, leading to severe side effects and the development of tumor escape variants during cancer treatment.
Innovation Solution
The development of a universal, modular anti-tag chimeric antigen receptor (UniCAR) system that allows immune cells to be retargeted using endogenous tags derived from human nuclear proteins, reducing immunogenicity and enabling targeting of multiple antigens with adjustable treatment duration.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Reliability
If conventional CAR technology is used to target antigens, then immune cells can recognize and attack target cells, but uncontrolled immune responses occur leading to severe side effects
Solution Approach 1:
The patent introduces a modular target recognition module (TRM) as an intermediary between the CAR and the target antigen. The TRM consists of a binding domain specific for a particular antigen and a tag domain. The CAR is engineered to recognize the tag rather than the antigen directly. This intermediary system allows controlled immune response because the CAR can be designed to recognize multiple different tags, providing built-in redundancy and control mechanisms that prevent uncontrolled immune activation against healthy tissues.
Solution Approach 2:
The patent changes the recognition parameter of the CAR from direct antigen binding to tag recognition. By modifying the CAR to recognize synthetic tags rather than natural antigens, the system gains improved control over immune activation. The tag-based recognition system allows for more precise parameter control of immune response intensity and duration, reducing harmful side effects while maintaining therapeutic efficacy.
2Adaptability or versatility
If conventional CAR technology targets a single antigen, then the CAR can be simple in design, but tumor escape variants develop due to loss of target antigen
Solution Approach 1:
The patent creates a universal CAR platform that can recognize multiple different tags through a single CAR design. The CAR is engineered with a binding domain that can interact with various tag variants, making it multi-functional. This universal approach allows the same CAR to target multiple different antigens by simply changing the TRM component, thereby preventing tumor escape variants without requiring complex multi-specific CAR designs. The system achieves versatility through modularity rather than complexity.
Solution Approach 2:
The patent segments the target recognition system into separate functional modules: the CAR component and the TRM component. The TRM itself is segmented into a binding domain and a tag domain. This segmentation allows independent optimization of each component and enables flexible recombination to target different antigens. The modular design simplifies the overall system while providing the ability to adapt to multiple targets, solving the contradiction between simplicity and versatility.
3Adaptability or versatility
If exogenous tags are used to redirect genetically modified T cells, then antigen targeting can be achieved, but the treatment becomes immunogenic and affects efficacy
Solution Approach 1:
The patent changes the origin and nature of the tags from exogenous to endogenous human sequences. The tags are designed based on human nuclear proteins, making them biologically compatible and non-immunogenic. This parameter change from foreign to self-derived tags maintains the redirection capability while eliminating the harmful immunogenic response that would compromise treatment efficacy.
Solution Approach 2:
The patent ensures homogeneity between the tag sequences and human biology by deriving tags from human nuclear proteins. This homogeneity makes the tags indistinguishable from self-antigens to the immune system, preventing immunogenicity. The uniform use of human-derived sequences throughout the system ensures biological compatibility while maintaining the ability to redirect immune cells to target antigens effectively.
Data Source
AI summary
The present invention relates to immune cell-based anti-cancer therapeutics and methods of using the therapeutics in the treatment of cancer.