Biodegradable Antigen-Presenting Particles for Targeted Treg Induction
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Solution Overview
Problem
Current autoimmune disease treatments often suppress the entire immune system, leaving patients vulnerable to infections, and there is a need for therapies that establish immune tolerance to specific self-antigens while maintaining immune system integrity.
Innovation Solution
Biodegradable particles composed of a polyester blend, such as PLGA and PBAE, encapsulating soluble proteins and surface-bound proteins, are designed to stimulate and expand regulatory T cells (Tregs) by providing 'Signal 1', 'Signal 2', and 'Signal 3' cues, mimicking natural antigen-presenting cells.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Object-affected harmful factors
If immunosuppressants are used to treat autoimmune diseases, then immune response to self-antigens is suppressed, but the entire immune system is weakened leaving patients vulnerable to infection
Solution Approach 1:
The patent segments the immune suppression function by using biodegradable particles that deliver immunosuppressive signals (Signal 1, Signal 2, and Signal 3 proteins) in a targeted manner to specific antigen-presenting cells, rather than using systemic immunosuppressants that affect the entire immune system. This allows selective suppression of autoimmunity while preserving overall immune function.
Solution Approach 2:
The patent introduces biodegradable particles as intermediary carriers that deliver multiple signaling proteins to antigen-presenting cells. These particles act as mediators between the therapeutic agent and the immune system, enabling controlled delivery of tolerance-inducing signals without directly suppressing the entire immune system.
2Object-affected harmful factors
If biodegradable particles with multiple surface-bound proteins are used to induce Tregs, then immune tolerance to self-antigens is enhanced, but particle complexity increases
Solution Approach 1:
The patent merges multiple functional proteins (Signal 1, Signal 2, and Signal 3 proteins) onto a single biodegradable particle platform. This combination allows the particle to simultaneously deliver multiple tolerance-inducing signals to antigen-presenting cells, enhancing Treg induction while maintaining a unified particle structure rather than requiring separate administrations of multiple agents.
Solution Approach 2:
The patent uses composite biodegradable particles made from polyester materials that can encapsulate and deliver multiple protein therapeutics. The composite structure allows integration of different signaling molecules within a single particle system, enabling complex immunomodulatory functions through a unified material platform.
3Productivity
If soluble proteins are encapsulated within particles and surface proteins are attached, then Treg stimulation and expansion are enhanced, but manufacturing complexity increases
Solution Approach 1:
The patent incorporates soluble proteins within the particle matrix during the particle fabrication process itself, rather than requiring separate encapsulation steps after particle formation. Surface proteins are also attached during or immediately after particle synthesis. This preliminary incorporation simplifies manufacturing by integrating multiple functionalization steps into the core particle fabrication process.
Data Source
AI summary
Biodegradable particles for interacting with immune cells to generate an immunosuppressive effect are disclosed. The biodegradable particle comprises a polyester or polyester blend with at least one soluble protein or small molecule encapsulated within the particle and at least two types of protein attached to a surface of the particle or to a coating on the surface thereof, which can be used to induce targeting regulatory T cells (Tregs). The at least two types of protein attached to a surface of the particle or to a coating on the surface thereof include a “Signal 1” protein that binds to an immune cell and a “Signal 2” protein that acts as a co-stimulatory molecule to immune cells. The encapsulated protein can be an interleukin and/or a cytokine. Methods of their use for treating a disease or condition, including an autoimmune disease, are disclosed.