Polymeric Particles for CAR-T Cell Proliferation
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Solution Overview
Problem
Current methods for delivering biomolecules are inefficient and non-specific, leading to unwanted side effects, and there is a need for improved in vivo half-life, expansion, and persistence of CAR-T cells for targeted therapies.
Innovation Solution
Development of polymeric particles functionalized with biomolecules for controlled surface presentation and encapsulation, along with CAR-antigen presenting particles to enhance CAR-T cell proliferation without significant cytokine production or exhaustion.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Measurement precision
If traditional biomolecule delivery methods are used, then biomolecules can be delivered to cells, but the delivery is inefficient and non-specific leading to unwanted side effects
Solution Approach 1:
The delivery system is segmented into multiple functional components: polymeric particles serve as the delivery vehicle, surface functionalization provides targeting capability, and core encapsulation enables controlled release. This segmentation allows each component to be optimized independently for specific delivery functions.
Solution Approach 2:
The polymeric particles exhibit local quality through surface functionalization with specific biomolecules at controlled densities and orientations. This creates localized binding sites that provide specific cell targeting while the bulk particle properties maintain delivery efficiency and stability.
2Duration of action of stationary object
If biomolecules are attached to solid supports to increase in vivo half-life, then half-life is extended, but controlling multiple biomolecules at specific ratios becomes complex
Solution Approach 1:
The polymeric particle serves multiple functions simultaneously: it acts as a solid support for biomolecule attachment, provides a controlled release matrix for encapsulated biomolecules, offers surface functionalization for targeting, and delivers mechanical stability for extended in vivo half-life. This multi-functionality simplifies the overall system while achieving multiple objectives.
Solution Approach 2:
The patent controls biomolecule ratios by adjusting parameters during the conjugation process, such as reactant concentrations, incubation conditions, and particle surface area. By changing these parameters, specific biomolecule densities and ratios are achieved on the particle surface without complex post-processing steps.
3Reliability
If CAR-T cells are activated to enhance killing potential, then tumor killing improves, but cytokine production and cell exhaustion increase
Solution Approach 1:
The polymeric particles are pre-functionalized with specific biomolecules that recognize and bind to CAR-T cell receptors before contact with tumor cells. This preliminary action ensures that when CAR-T cells encounter tumor targets, the particles are already positioned to deliver biomolecules in a controlled manner, enhancing killing potential while regulating cytokine release through the particle matrix structure.
Solution Approach 2:
The polymeric particle acts as an intermediary between the CAR-T cell and the tumor cell. It presents biomolecules on its surface that mediate the interaction, allowing controlled signal transmission to the CAR-T cell while the particle matrix regulates the release rate of encapsulated biomolecules, thereby modulating cytokine production and preventing excessive cell exhaustion.
Data Source
Figure 1A~1B
Figure 1C~1D
Figure 1E
AI summary
The present disclosure provides polymeric particles comprising biomolecules of interest attached thereto, methods for using the same, and methods for making the same. The surface of the polymeric particles can be functionalized by attaching multiple different biomolecules of interest in a desired ratio for co-presentation. In addition, the polymeric particles may also encapsulate biomolecules, such as, therapeutic nucleic acids, peptide and/or polypeptides for release in vivo. The present disclosure also provide synthetic particles and methods for enhancing proliferation of CAR-T cells. Additionally, the present disclosure provide biomolecule-coated films and methods.