Soluble CD52 Glycoprotein T-Cell Suppression

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Solution Overview

Problem

Current methods lack effective mechanisms to suppress T-cell activation, particularly in autoimmune diseases and conditions mediated by effector T-cell function, and there is a lack of specific markers and understanding of human regulatory T-cell function.

Innovation Solution

The use of soluble CD52 glycoprotein or fusion proteins, which are capable of suppressing effector T-cell function by binding to Siglec-10, thereby reducing immune responses and inducing tolerance to autoantigens, is proposed, along with methods for detecting susceptibility to diseases mediated by effector T-cell function.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Reliability

If soluble CD52 glycoprotein is used to suppress T-cell activation, then immune response suppression is improved, but specificity of Treg cell identification deteriorates due to lack of specific cell surface markers

Engineering Contradiction:
Improveimmune response suppressionVSAvoidspecific cell surface markers
Core Design Contradiction:
ReliabilityVSDevice complexity

Solution Approach 1:

The patent uses soluble CD52 glycoprotein as an intermediary mediator to suppress T-cell activation. Instead of directly using cell surface markers for identification, the invention employs the soluble form of CD52 that can bind to and suppress effector T-cells, thereby resolving the contradiction between achieving reliable immune suppression and dealing with the complexity of specific marker identification

Inventive Principle:
Principle #24Intermediary (Mediator)

Solution Approach 2:

The invention changes the state of CD52 from membrane-bound to soluble form. This parameter change allows CD52 to function as a soluble mediator that can suppress T-cell activation without requiring specific cell surface marker identification, thus improving immune response suppression while avoiding the complexity of marker-specific approaches

Inventive Principle:
Principle #35Parameter changes

2Reliability

If CD4+CD25+ Treg cells are used for suppression, then suppression mechanism is improved, but understanding of human Treg cell function deteriorates due to limited knowledge of in vivo function

Engineering Contradiction:
Improvesuppression mechanismVSAvoidin vivo function understanding
Core Design Contradiction:
ReliabilityVSLoss of information

Solution Approach 1:

The patent extracts the suppressive function from the complex CD4+CD25+ Treg cell population and isolates it into a specific soluble mediator (soluble CD52). This extraction allows the suppressive mechanism to be studied and applied independently, improving our understanding of the actual in vivo suppression function without the confounding variables of polyspecific Treg populations

Inventive Principle:
Principle #2Taking out (Extraction)

3Adaptability or versatility

If polyspecific Treg cell populations are used, then broad suppression is improved, but antigen-specific tolerance deteriorates due to inability to target specific autoantigens

Engineering Contradiction:
Improvebroad suppressionVSAvoidantigen-specific tolerance
Core Design Contradiction:
Adaptability or versatilityVSReliability

Solution Approach 1:

The patent segments the broad suppressive function into antigen-specific components by using soluble CD52 that can be combined with specific autoantigens. This segmentation allows the system to maintain broad suppressive capability while also achieving antigen-specific tolerance, resolving the contradiction between versatility and reliability in different therapeutic contexts

Inventive Principle:
Principle #1Segmentation

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 soluble CD52 glycoprotein effectively suppresses T-cell activation and immune responses, potentially treating autoimmune diseases and conditions by inducing tolerance to autoantigens, and diagnosing susceptibility through CD52 level detection.

Implementation Method 1

capable of suppressing effector T-cell function by binding to Siglec-10

Methodology Applied
Scientific EffectBinding interaction:

Data Source

PatentEP3456338B1Soluble CD52 for use in the treatment or prevention of multiple sclerosis or rheumatoid arthritis
Publication Date: 2020.07.29 THE WALTER AND ELIZA HALL INSTITUTE OF MEDECAL RESEARCH
  • EP3456338B1 patent drawingFigure 1A~1B
  • EP3456338B1 patent drawingFigure 2A~2A3
  • EP3456338B1 patent drawingFigure 2B~2C

AI summary

The present disclosure relates to a soluble CD52 glycoprotein and its use in treating diseases regulated by effector T-cells, for example autoimmune diseases such as type 1 diabetes. The present disclosure also relates to fusion proteins comprising the soluble glycoprotein, to cells expressing high levels of CD52, and to diagnostic methods based on the detection of CD52 expression levels in a subject.