Helios Targeting for Treg Suppression Modulation

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Solution Overview

Problem

Current methods for modulating immune responses, particularly in treating neoplasia and autoimmune diseases, are inadequate due to limitations in regulating CD4+CD25+ regulatory T cell (Treg) suppressive activity, which hampers effective antitumor immune responses and exacerbates autoimmune conditions.

Innovation Solution

The use of agents that alter Helios expression or activity in CD4+CD25+ T cells to modulate their suppressive function, either by increasing or reducing Treg activity, thereby enhancing or suppressing immune responses as needed, using siRNA, aptamers, and other nucleic acid molecules to target Helios and disrupt its interaction with the FoxP3 promoter.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Reliability

If conventional methods are used to modulate immune response, then general immune modulation is achieved, but Treg suppressive activity cannot be effectively regulated

Engineering Contradiction:

Improveefficacy of immune responseVSAvoidability to regulate Treg suppressive activity

Core Design Contradiction:

ReliabilityVSAdaptability or versatility

Solution Approach 1:

The invention changes the molecular parameter by targeting Helios expression levels in Tregs. By using agents that specifically alter Helios expression, the patent achieves precise control over Treg suppressive activity, thereby resolving the contradiction between reliable immune modulation and the ability to regulate Treg function.

Inventive Principle:

Principle #35Parameter changes

Solution Approach 2:

The invention introduces Helios as an intermediary target between conventional immune modulation methods and Treg suppressive activity. By using agents that specifically bind to or alter Helios expression, the patent creates a controlled pathway to regulate Treg function without directly interfering with other immune parameters.

Inventive Principle:

Principle #24Intermediary (Mediator)

2Object-affected harmful factors

If Treg suppressive activity is increased to maintain immune tolerance, then autoimmune disease is reduced, but antitumor immune response is suppressed

Engineering Contradiction:

Improveautoimmune disease severityVSAvoidsuppression of antitumor immune response

Core Design Contradiction:

Object-affected harmful factorsVSObject-generated harmful factors

Solution Approach 1:

The invention makes Treg suppressive activity dynamic and conditionally可调 by targeting Helios expression. This allows the immune system to adapt Treg function based on the specific pathological context - reducing suppression in cancer while maintaining it in autoimmune conditions, thereby resolving the contradiction between protecting against autoimmunity and enabling antitumor immunity.

Inventive Principle:

Principle #15Dynamics

Solution Approach 2:

The invention applies local quality control by using agents that can differentially modulate Helios expression in different tissue contexts or disease states. This enables selective reduction of Treg suppressive activity in tumor microenvironments while preserving it in autoimmune-prone tissues, resolving the contradiction between these opposing therapeutic needs.

Inventive Principle:

Principle #3Local quality

3Productivity

If Treg suppressive activity is reduced to enhance antitumor immune response, then cancer treatment efficacy is improved, but immune homeostasis and tolerance are compromised

Engineering Contradiction:

Improveefficacy of antitumor immune responseVSAvoidimmune homeostasis

Core Design Contradiction:

ProductivityVSStability of the object's composition

Solution Approach 1:

The invention applies partial action by using agents that reduce Helios expression to a controlled extent rather than completely eliminating it. This partial modulation is sufficient to enhance antitumor immune response while leaving enough Treg function intact to maintain immune homeostasis and prevent autoimmunity, thereby resolving the contradiction between cancer treatment efficacy and immune stability.

Inventive Principle:

Principle #16Partial or excessive action

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

This approach effectively modulates Treg activity, enhancing antitumor immune responses and reducing autoimmune disease severity by specifically targeting Helios to alter Treg suppressive functions, thereby improving treatment outcomes for neoplasia and autoimmune disorders.

Implementation Method 1

using siRNA, aptamers, and other nucleic acid molecules to target Helios and disrupt its interaction with the FoxP3 promoter

Methodology Applied

Scientific EffectRNA interference:

Data Source

PatentUS10329617B2Compositions and methods for modulating an immune response

Publication Date: 2019.06.25 JOHNS HOPKINS UNIVERSITY

AI summary

The invention generally features compositions and methods for modulating an immune response. In particular embodiments, such compositions and methods modulate regulatory T cell suppressive activity.