Antigen-Specific Treg Generation via Zwitterionic Polysaccharide Conjugates

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Solution Overview

Problem

Current methods fail to effectively generate antigen-specific anti-inflammatory regulatory T cells to inhibit antigen-specific pro-inflammatory immune responses, which are crucial for maintaining immune homeostasis and preventing autoimmune diseases.

Innovation Solution

The generation of antigen-specific anti-inflammatory regulatory T cells is achieved by contacting T cells or antigen-presenting cells with zwitterionic polysaccharides conjugated to antigens or engineered Bacteroides fragilis, under specific conditions, to induce T cells capable of inhibiting inflammatory responses.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Reliability

If conventional methods are used to generate regulatory T cells, then general immune suppression may occur, but antigen-specific suppression capability is insufficient

Engineering Contradiction:
Improveantigen-specific suppression capabilityVSAvoidgeneration method complexity
Core Design Contradiction:
ReliabilityVSEase of manufacture

Solution Approach 1:

The patent uses zwitterionic polysaccharides as intermediary molecules that conjugate to antigens, enabling selective presentation to T cells. This mediator approach allows antigen-specific Treg generation without requiring complex in vitro differentiation protocols, thus improving reliability while maintaining ease of manufacture.

Inventive Principle:
Principle #24Intermediary (Mediator)

Solution Approach 2:

The patent modifies the chemical parameters of polysaccharides by introducing zwitterionic groups, which fundamentally changes their interaction properties with T cells and antigens. This parameter change enables selective activation of antigen-specific Tregs through simple contact, avoiding complex manufacturing procedures.

Inventive Principle:
Principle #35Parameter changes

2Object-affected harmful factors

If strong immunosuppression is achieved, then inflammatory responses are controlled, but immune homeostasis and protective immunity may be compromised

Engineering Contradiction:
Improveinflammatory response controlVSAvoidimmune homeostasis maintenance
Core Design Contradiction:
Object-affected harmful factorsVSReliability

Solution Approach 1:

The patent applies local quality by making the immunosuppression effect antigen-specific rather than systemic. The zwitterionic polysaccharide-antigen conjugates ensure that suppression is localized to specific antigen-targeted T cells, controlling inflammation while preserving overall immune homeostasis and protective immunity against unrelated pathogens.

Inventive Principle:
Principle #3Local quality

3Manufacturing precision

If antigen-specific Tregs are generated through complex protocols, then suppression specificity is improved, but production efficiency and scalability are reduced

Engineering Contradiction:
Improveantigen-specificity precisionVSAvoidTreg generation efficiency
Core Design Contradiction:
Manufacturing precisionVSProductivity

Solution Approach 1:

The patent performs preliminary action by pre-conjugating antigens to zwitterionic polysaccharides before T cell contact. This pre-prepared conjugate can directly induce antigen-specific Tregs through simple co-culture, eliminating the need for complex step-by-step differentiation protocols and significantly improving production efficiency while maintaining high antigen-specificity precision.

Inventive Principle:
Principle #10Preliminary action

Data Source

PatentUS11103566B2Antigen specific Tregs and related compositions, methods and systems
Publication Date: 2021.08.31 CALIFORNIA INST OF TECH
  • US11103566B2 patent drawing
  • US11103566B2 patent drawing
  • US11103566B2 patent drawing

AI summary

Antigen specific regulatory T cells are described and related compositions, methods and systems. Methods to generate an antigen specific anti-inflammatory regulatory T cell is provided, the method comprising contacting either a T cell or an antigen presenting cell with a zwitterionic polysaccharide conjugated to the antigen for a time and under condition to generate an antigen specific regulatory T cell that is capable of inhibiting a pro-inflammatory response against the antigen.