Astragalus Polysaccharide Extract Repolarizes Macrophages

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Solution Overview

Problem

Current cancer immunotherapy methods are limited in effectively enhancing the functional maturation of dendritic cells and repolarizing macrophages towards the M1 phenotype, which are crucial for antitumor immunity, as they often rely on suboptimal differentiation protocols and fail to adequately address the pro-tumoral functions of tumor-associated macrophages.

Innovation Solution

Administration of a polysaccharide extract from Astragalus membranaceus, with a specific arabinose:galactose ratio and molecular weight range, to enhance the functional maturation of dendritic cells and repolarize macrophages towards the M1 phenotype, thereby reducing tumor-associated macrophage recruitment, invasion, angiogenesis, and proliferation.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Reliability

If classical differentiation protocols using IL-4 and GM-CSF are used for dendritic cell therapy, then dendritic cells can be generated, but the functional maturation and immunostimulatory potential are insufficient

Engineering Contradiction:

Improvefunctional maturation of dendritic cellsVSAvoiddifferentiation protocol complexity

Core Design Contradiction:

ReliabilityVSEase of manufacture

Solution Approach 1:

The patent replaces IL-4 with IL-15 or IFNα in the differentiation protocol, changing the cytokine parameters to achieve superior functional maturation of dendritic cells. This parameter change results in enhanced immunostimulatory potential and improved anti-tumor function while maintaining protocol feasibility

Inventive Principle:

Principle #35Parameter changes

Solution Approach 2:

The patent uses a combination of GM-CSF with either IL-15 or IFNα during the differentiation phase, creating a composite cytokine treatment regimen. This composite approach synergistically enhances dendritic cell maturation markers (CD80, CD83, CD86, CD103) and functional capabilities beyond what single cytokines achieve

Inventive Principle:

Principle #40Composite materials

2Reliability

If tumor associated macrophages are present in high numbers, then tumor microenvironment is modulated for tumor progression, but immunotherapy effectiveness is reduced

Engineering Contradiction:

Improveantitumor immunityVSAvoidpro-tumoral functions of TAMs

Core Design Contradiction:

ReliabilityVSObject-generated harmful factors

Solution Approach 1:

The patent inverts the harmful M2 macrophage phenotype into the beneficial M1 phenotype by administering polysaccharide extracts that trigger macrophage polarization reversal. This phenotype inversion converts tumor-promoting macrophages into tumor-fighting macrophages that produce pro-inflammatory cytokines and enhance antitumor immunity

Inventive Principle:

Principle #13The other way round (Inversion)

Solution Approach 2:

The patent converts the harmful presence of tumor-associated macrophages into a beneficial anti-tumor force by using polysaccharide extracts to reprogram their function. The same macrophage population that previously supported tumor progression is transformed into cells that produce IL-12, TNF-α, and other antitumor factors

Inventive Principle:

Principle #22Blessing in disguise (Convert harm into benefit)

Data Source

PatentUS10478468B2Method for enhancing effect of immunotherapy for cancer

Publication Date: 2019.11.19 PHYTOHEALTH CORP

AI summary

Disclosed is a method for enhancing the effect of an immunotherapy for cancer in a subject, comprising administering to the subject an effective amount of a polysaccharide extract of Astragalus membranaceus. Also disclosed is a method for increasing a subject's pool of M1 macrophages, wherein the subject is suffering from one or more conditions associated with undesirable M2 macrophage activation, the method comprising administering to the subject an effective amount of a polysaccharide extract of Astragalus membranaceus.