O-Acetylated Beta-1,6-Glucan Immunomodulation
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Solution Overview
Problem
Current immunotherapies face challenges in effectively modulating immune responses against infectious agents, cancers, and autoimmune disorders, particularly in enhancing phagocytosis and reactive oxygen species production by neutrophils, which are crucial for fungal and bacterial infections.
Innovation Solution
A composition enriched with β-1,6-glucan, specifically O-acetylated β-1,6-glucan, is used, either isolated from lichens or synthesized, which can be conjugated to particles or used as an adjuvant to stimulate immune responses, enhance phagocytosis, and induce the production of reactive oxygen species in neutrophils.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Reliability
If conventional immunotherapies are used to modulate immune responses, then immune modulation is achieved, but the effectiveness against infectious agents, cancers, and autoimmune disorders is insufficient
Solution Approach 1:
The patent modifies the chemical structure of β-glucan by introducing O-acetylation at specific positions (C2, C3, or C6) of the glucose units. This parameter change enhances the immunomodulatory activity and specific binding to Dectin-1 receptor, thereby improving the effectiveness of the therapy while maintaining safety profile
Solution Approach 2:
The invention creates a composite structure by conjugating O-acetylated β-1,6-glucan to particulate carriers. This composite approach combines the immunomodulatory properties of the glucan with the targeted delivery and adjuvant effects of particles, resulting in enhanced immune response modulation against various pathologies
2Reliability
If β-1,6-glucan is used to enhance phagocytosis and reactive oxygen species production, then anti-infective activity is improved, but specificity and control over immune modulation are reduced
Solution Approach 1:
The patent introduces O-acetylation at specific local positions (C2, C3, or C6) of the β-1,6-glucan chain rather than uniform modification. This localized chemical modification creates specific binding sites for Dectin-1 receptor, enhancing both the anti-infective activity and the specificity of the immune modulation response
Solution Approach 2:
The O-acetylated β-1,6-glucan acts as an intermediary that specifically binds to Dectin-1 receptor on immune cells, serving as a bridge between the glucan structure and the immune response. This intermediary interaction enables controlled and specific modulation of phagocytosis and reactive oxygen species production
3Reliability
If fungal cell walls are used as immunostimulants, then anti-tumor and anti-infective effects are observed, but the purity and consistency of the immunomodulatory components are compromised
Solution Approach 1:
The patent extracts and isolates β-1,6-glucan from fungal cell walls, separating it from other complex components such as chitin, proteins, and lipids. This extraction process purifies the immunomodulatory component while maintaining its biological activity, enabling consistent and controlled immunotherapy
Solution Approach 2:
The invention modifies the purified β-1,6-glucan by introducing O-acetylation at specific positions. This parameter change enhances the immunomodulatory activity and binding specificity while maintaining the purity of the isolated component, resolving the contradiction between purity and effectiveness
Applied Scientific Principles
This section explains which scientific principles are used to turn an abstract innovation direction into a practical engineering solution.
Function Achieved in This Case
The β-1,6-glucan composition effectively stimulates antigen-specific immune responses, enhances phagocytosis, and induces the production of reactive oxygen species, thereby improving the body's ability to combat infections and tumors, and can be used to treat autoimmune disorders by modulating immune activity.
Implementation Method 1
Recognition of β-glucans by macrophages is carried out mainly through Dectin-1 with the cooperation of TLRs, including TLR2
Implementation Method 2
CR3 has a lectin domain that mediates increased neutrophil motility towards a mixture of β-1,3-glucan and β-1,6-glucan
Implementation Method 3
enhances phagocytosis, and induces the production of reactive oxygen species in neutrophils
Data Source
AI summary
This invention is directed to β-1-6-glucans, compositions and devices comprising the same, and methods of use thereof in modulating immune responses. The β-1-6-glucans of certain embodiments of the invention are enriched for O-acetylated groups and/or conjugated to a solid support or linked to a targeting moiety.