Reversed Universal CAR System for Multi-Antigen Targeting
Find Innovative SolutionsGenerate Solutions
Solution Overview
Problem
Conventional CAR technology faces challenges such as uncontrolled immune responses, severe side effects, tumor lysis syndrome, cytokine release syndrome, and the limitation of targeting a single antigen, leading to restricted applications in cancer and autoimmune disorder treatments.
Innovation Solution
The development of a reversed universal, modular chimeric antigen receptor (RevCAR) system that allows immune cells to recognize multiple antigens using a peptide epitope tag and adapter modules, reducing the risk of cross-reactivity and enabling flexible and controlled retargeting.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Reliability
If conventional CAR technology is used to target antigens, then immune cells can kill target cells, but unexpected cross-reactivity with healthy tissue antigens causes severe side effects and organ damage
Solution Approach 1:
The patent introduces an adapter molecule as an intermediary component that acts as a bridge between the CAR-T cell and the target antigen. The adapter molecule consists of a binding domain specific for the target antigen and a tag domain that binds to the CAR receptor. This intermediary structure allows the CAR-T cell to recognize and kill target cells through the adapter molecule, while the CAR receptor itself does not directly bind to the target antigen, thereby reducing the risk of unexpected cross-reactivity with healthy tissue.
2Reliability
If conventional CAR-T cells are engineered to express a single antigen target, then they can effectively kill that specific target, but tumor escape variants emerge that have lost the target antigen
Solution Approach 1:
The patent designs the CAR receptor to be universal by incorporating a tag domain that can bind to different adapter molecules targeting various antigens. The CAR-T cell expresses this universal CAR receptor, and by introducing different adapter molecules with different antigen-specific binding domains, the same CAR-T cell can be redirected to target multiple different antigens including CD19, CD20, CD22, and others, preventing tumor escape variants from developing.
3Productivity
If CAR-T cells undergo vigorous expansion in the presence of heavy tumor burden, then they can amplify the immune response, but this leads to tumor lysis syndrome and cytokine release syndrome
Solution Approach 1:
The patent implements dynamic control of CAR-T cell activation and expansion through the adapter molecule system. The CAR-T cell remains in a quiescent state until the adapter molecule is introduced to provide the specific antigen target signal. This allows for controlled activation and expansion timing, enabling the immune response to be amplified when needed while avoiding uncontrolled expansion that leads to cytokine release syndrome and tumor lysis syndrome.
4Adaptability or versatility
If conventional CAR technology is used, then B cell malignancies can be treated, but the treatment modality is restricted to very few indications due to safety issues
Solution Approach 1:
The patent segments the CAR system into three separate functional components: (1) the CAR receptor expressed by the T cell containing a tag domain, (2) the adapter molecule with an antigen-specific binding domain and a tag-binding domain, and (3) the signaling domain. This segmentation allows independent optimization of each component - the CAR receptor can be designed for safety and control, the adapter molecule provides antigen specificity, and the signaling domain ensures proper T cell activation. This modular architecture enables safe application across multiple disease indications by simply changing the adapter molecule while keeping the CAR-T cell constant.
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.