Antigen-MHC Nanoparticles for Selective Regulatory T Cell Expansion

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Solution Overview

Problem

Current therapies fail to selectively blunt autoimmune responses without impairing systemic immunity, as the lymphocyte specificities involved in autoimmune diseases are complex and incompletely defined.

Innovation Solution

Administration of antigen-MHC class II-nanoparticle complexes to expand and develop populations of anti-pathogenic autoreactive T cells and B cells, specifically targeting autoantigens relevant to autoimmune diseases like diabetes and multiple sclerosis, using nanoparticles with controlled antigen-MHC density and composition.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Object-affected harmful factors

If conventional immunotherapy is used to suppress autoimmune responses, then autoimmune activity is reduced, but systemic immunity is impaired

Engineering Contradiction:

Improveautoimmune responseVSAvoidsystemic immunity

Core Design Contradiction:

Object-affected harmful factorsVSReliability

Solution Approach 1:

The nanoparticle complexes deliver antigens specifically to dendritic cells in lymph nodes, creating a localized immunomodulatory effect. The antigen-MHC class II complexes on nanoparticle surfaces are presented in a controlled manner to selectively activate regulatory T cells without broadly suppressing the immune system, thus treating autoimmune disease while preserving systemic immunity.

Inventive Principle:

Principle #3Local quality

Solution Approach 2:

The nanoparticle acts as an intermediary carrier that presents antigen-MHC class II complexes to the immune system in a controlled fashion. This intermediary structure enables selective expansion of regulatory T cells through dendritic cell presentation, mediating immune modulation without the broad suppressive effects of conventional therapies.

Inventive Principle:

Principle #24Intermediary (Mediator)

2Productivity

If high density of antigen-MHC complexes is used on nanoparticles, then immune activation is enhanced, but off-target effects increase

Engineering Contradiction:

Improveimmune activation efficiencyVSAvoidoff-target immune effects

Core Design Contradiction:

ProductivityVSObject-generated harmful factors

Solution Approach 1:

The patent optimizes the density of antigen-MHC class II complexes on nanoparticle surfaces to achieve therapeutic efficacy while minimizing off-target effects. By controlling the ratio of antigen-MHC complexes to nanoparticle surface area, the system achieves sufficient immune activation of regulatory T cells without causing excessive or inappropriate immune responses.

Inventive Principle:

Principle #35Parameter changes

Solution Approach 2:

The patent replaces non-specific immune stimulation with a targeted presentation mechanism. Instead of using high doses of free antigen that would cause off-target effects, the antigen is mechanically organized on nanoparticle surfaces at controlled densities, enabling specific recognition by dendritic cells and subsequent selective T cell activation.

Inventive Principle:

Principle #28Mechanics substitution (Replace mechanical system)

Data Source

PatentUS20220401534A1Methods and compositions for sustained immunotherapy

Publication Date: 2022.12.22 UTI LIMITED PARTNERSHIP

AI summary

This disclosure provides methods of making functionalized PEG iron oxide nanoparticles.