Modular CAR-T Cell Targeting With RNA Docketing Compounds
Find Innovative SolutionsGenerate Solutions
Solution Overview
Problem
Existing methods struggle to selectively deliver therapeutic or diagnostic agents to specific sites in the body, such as cancer cells, using immune effector cells effectively.
Innovation Solution
Genetically modify immune effector cells to express a chimeric antigen receptor (CAR) and administer RNA encoding peptides or polypeptides with binding moieties that target cancer cells, allowing the immune effector cells to bind and kill diseased cells.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Measurement precision
If existing methods are used to deliver therapeutic agents to specific sites, then delivery can be achieved, but selective targeting precision is insufficient
Solution Approach 1:
The patent introduces a docketing compound as an intermediary that bridges the gap between immune effector cells and target cells. The docketing compound comprises a binding moiety for the CAR (chimeric antigen receptor) on immune effector cells and a primary targeting moiety that binds to target cells, thereby mediating precise and reliable delivery of therapeutic agents to specific sites.
Solution Approach 2:
The patent segments the targeting system into distinct functional components: the CAR on immune effector cells, the docketing compound with separate binding moiety and primary targeting moiety, and the target cell antigen. This segmentation allows each component to be optimized independently while working together to achieve high precision and reliability in targeted delivery.
2Adaptability or versatility
If multiple types of immune effector cells are used to target different cancer cells, then targeting coverage is improved, but system complexity increases
Solution Approach 1:
The patent creates a universal immune effector cell system where a single type of immune effector cell expressing a CAR can target multiple different cancer cell types by using different docketing compounds. The docketing compound serves as a versatile adapter that can be configured with different primary targeting moieties to recognize various target antigens, thereby providing broad targeting coverage without requiring multiple immune effector cell types.
Solution Approach 2:
The docketing compound acts as a programmable intermediary that decouples the immune effector cell from the specific target antigen. By changing the primary targeting moiety on the docketing compound while keeping the CAR-expressing immune effector cell constant, the system can adapt to target different cancer types, reducing complexity while maintaining versatility.
3Productivity
If immune effector cells are administered directly to target cancer cells, then treatment can proceed, but expansion and activation of immune effector cells is insufficient
Solution Approach 1:
The patent implements preliminary action by first administering an activation compound that expresses a binding moiety for the CAR on antigen-presenting cells before or concurrent with administering the docketing compound. This preliminary activation of immune effector cells through binding to the activation compound stimulates their expansion and enhances their therapeutic efficacy before they engage with the target cancer cells.
Solution Approach 2:
The system incorporates feedback mechanisms where binding of the CAR to the activation compound on antigen-presenting cells triggers immune effector cell activation and proliferation. This feedback loop ensures that the immune response is amplified in proportion to the presence of target antigens, thereby increasing treatment efficacy while maintaining controlled expansion of immune effector cells.
Data Source
AI summary
The invention relates to agents and methods for activation of immune effector cells and targeted delivery of the activated immune effector cells to target cells. In one embodiment, the invention involves providing to a subject immune effector cells genetically modified to express a chimeric antigen receptor (CAR). In one embodiment, the invention involves administering RNA encoding a peptide or polypeptide (activation compound) comprising a binding moiety for the CAR and administering RNA encoding a peptide or polypeptide (docketing compound) comprising a binding moiety binding to target cells (primary targeting moiety) and a further binding moiety for the CAR (secondary target).