ICOSL-Overexpressing Mesenchymal Stem Cells for Regulatory T Cell Induction

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Solution Overview

Problem

Current therapeutic agents for autoimmune diseases and T-cell mediated diseases lack a precise mechanism for inducing regulatory T cells, which are crucial for maintaining self-tolerance and preventing autoimmune responses.

Innovation Solution

A pharmaceutical composition comprising induced T cell co-stimulator ligand (ICOSL)-overexpressing clonal mesenchymal stem cells that induce the differentiation of CD4+ T cells into regulatory T cells, utilizing ICOSL to promote the PI3K-Akt signaling pathway and inhibit inflammatory or autoimmune responses.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Reliability

If conventional therapeutic agents are used for autoimmune diseases, then treatment is provided, but the mechanism for inducing regulatory T cells is not precise

Engineering Contradiction:

Improveprecision of regulatory T cell induction mechanismVSAvoidcomplexity of therapeutic mechanism

Core Design Contradiction:

ReliabilityVSDevice complexity

Solution Approach 1:

The patent uses ICOSL (inducible T cell co-stimulator ligand) as an intermediary molecule to mediate the interaction between mesenchymal stem cells and T cells. This intermediary enables precise induction of regulatory T cells through a specific signaling pathway, resolving the contradiction by providing a defined molecular mechanism rather than using conventional non-specific immunosuppressants

Inventive Principle:

Principle #24Intermediary (Mediator)

Solution Approach 2:

The patent employs IL-1β to induce changes in the expression parameters of ICOSL on mesenchymal stem cells. By controlling the induction parameters (IL-1β treatment conditions), the system achieves precise regulation of T cell differentiation into regulatory T cells, thereby improving the precision of the therapeutic mechanism

Inventive Principle:

Principle #35Parameter changes

2Reliability

If mesenchymal stem cells are used to regulate immune responses, then immunoregulatory ability is provided, but the specific regulator and action mechanism are not well understood

Engineering Contradiction:

Improvespecificity of regulatory mechanismVSAvoidknowledge of action mechanism

Core Design Contradiction:

ReliabilityVSLoss of information

Solution Approach 1:

The patent identifies ICOSL as the specific intermediary molecule on mesenchymal stem cells that mediates regulatory T cell induction. This identification fills the knowledge gap about the specific regulator, and the downstream signaling pathway analysis provides information about the action mechanism, thereby resolving both the specificity and knowledge loss issues

Inventive Principle:

Principle #24Intermediary (Mediator)

3Reliability

If self-tolerance is maintained to prevent autoimmune diseases, then immune unresponsiveness to self-antigens is achieved, but the ability to recognize and eliminate non-self-antigens may be compromised

Engineering Contradiction:

Improveself-tolerance maintenanceVSAvoidimmune response capability

Core Design Contradiction:

ReliabilityVSAdaptability or versatility

Solution Approach 1:

The patent induces differentiation of specific CD4+ T cell subsets into regulatory T cells with localized suppressive function. This local quality approach allows enhanced self-tolerance through increased Treg populations while preserving the functional capabilities of other T cell subsets to recognize and respond to non-self-antigens, thus resolving the contradiction between tolerance and adaptability

Inventive Principle:

Principle #3Local quality

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

Effectively induces the differentiation and proliferation of regulatory T cells, thereby preventing or treating T cell-mediated diseases by inhibiting autoimmune and inflammatory responses, as demonstrated by increased expression of ICOS, FoxP3, and IL-10 production.

Implementation Method 1

utilizing ICOSL to promote the PI3K-Akt signaling pathway and inhibit inflammatory or autoimmune responses

Methodology Applied

Scientific EffectPI3K-Akt signaling pathway:

Implementation Method 2

the induced T cell co-stimulator ligand (ICOSL) on the mesenchymal stem cell surface can induce CD4+

Methodology Applied

Scientific EffectICOS-ICOSL interaction:

Data Source

PatentEP3388514B1Pharmaceutical composition for preventing or treating regulatory t cell-mediated diseases

Publication Date: 2023.10.25 SCM LIFESCI CO LTD

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AI summary

The present invention relates to a composition and a method for inducing CD4+ T cells to differentiate into regulatory T cells and proliferate through an induced T cell co-stimulator ligand (ICOSL) or an ICOSL- overexpressing mesenchymal stem cell and for preventing or treating regulatory T cell-mediated diseases. The induced T cell co-stimulator ligand (ICOSL) or ICOSL-overexpressing mesenchymal stem cell according to the present invention effectively suppresses the proliferation of PBMCs, induces the expression of an ICOS in regulatory T cells, thereby inducing the differentiation and proliferation of the regulatory T cells through a PI3K-Akt mechanism, and thus can effectively prevent, treat, or enhance regulatory T cell-mediated diseases.