Modulating Treg Function via Brd7 and Brd9 Epigenetic Targets

Solution Overview

Problem

Current treatments for autoimmune diseases and cancer face challenges due to the immunosuppressive function of regulatory T (Treg) cells, which can suppress anti-tumor responses and exacerbate autoimmune conditions, highlighting the need for targeted modulation of Treg cell activity.

Innovation Solution

Administering therapeutically effective amounts of agents that modulate the expression or activity of Brd7, Brd9, and Pbrm1 in Treg cells, either by increasing or decreasing their levels, using techniques such as activators, expression vectors, genome editing, or small molecule inhibitors, to enhance or suppress Treg suppressor activity.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Reliability

If Treg suppressor activity is increased to treat autoimmune diseases, then autoimmune disease symptoms are improved, but anti-tumor immune responses are suppressed

Engineering Contradiction:

Improveautoimmune disease treatment efficacyVSAvoidsuppression of anti-tumor immune responses

Core Design Contradiction:

ReliabilityVSObject-affected harmful factors

Solution Approach 1:

The patent applies local quality by differentially modulating Treg cell function in different tissue compartments. In autoimmune disease contexts, Treg suppressor activity is enhanced to control auto-reactive T cells. In cancer contexts, Treg suppressor activity is reduced to allow anti-tumor immune responses. This spatial and functional differentiation resolves the contradiction by allowing opposite modulation strategies in different disease contexts.

Inventive Principle:

Principle #3Local quality

Solution Approach 2:

The patent employs dynamic modulation of Treg cell function through reversible epigenetic modifications. By targeting chromatin remodelers and histone modifiers, the system can dynamically adjust Treg suppressor activity based on disease context. This dynamic control allows the same biological system to exhibit different functional states (high suppressor activity for autoimmune diseases, low suppressor activity for cancer) without permanent genetic changes.

Inventive Principle:

Principle #15Dynamics

2Reliability

If Treg suppressor activity is decreased to enhance anti-tumor responses, then cancer treatment efficacy is improved, but autoimmune disease control is worsened

Engineering Contradiction:

Improvecancer treatment efficacyVSAvoidloss of autoimmune disease control

Core Design Contradiction:

ReliabilityVSObject-affected harmful factors

Solution Approach 1:

The patent applies local quality by differentially modulating Treg cell function in different tissue compartments. In autoimmune disease contexts, Treg suppressor activity is enhanced to control auto-reactive T cells. In cancer contexts, Treg suppressor activity is reduced to allow anti-tumor immune responses. This spatial and functional differentiation resolves the contradiction by allowing opposite modulation strategies in different disease contexts.

Inventive Principle:

Principle #3Local quality

Solution Approach 2:

The patent employs dynamic modulation of Treg cell function through reversible epigenetic modifications. By targeting chromatin remodelers and histone modifiers, the system can dynamically adjust Treg suppressor activity based on disease context. This dynamic control allows the same biological system to exhibit different functional states (high suppressor activity for autoimmune diseases, low suppressor activity for cancer) without permanent genetic changes.

Inventive Principle:

Principle #15Dynamics

3Stability of the object's composition

If broad immunosuppression is used to treat autoimmune diseases, then immune homeostasis is improved, but anti-cancer immunity is suppressed

Engineering Contradiction:

Improveimmune homeostasisVSAvoidsuppression of anti-tumor responses

Core Design Contradiction:

Stability of the object's compositionVSObject-affected harmful factors

Solution Approach 1:

The patent moves away from broad immunosuppression toward localized modulation of Treg cell function. By targeting specific epigenetic regulators in Treg cells, the system can selectively enhance suppressor activity in autoimmune contexts without broadly suppressing the entire immune system. This targeted approach preserves anti-tumor immunity while maintaining immune homeostasis in autoimmune diseases.

Inventive Principle:

Principle #3Local quality

Solution Approach 2:

The patent applies parameter changes by modifying specific epigenetic parameters (chromatin accessibility, histone modifications) in Treg cells rather than broadly suppressing immune function. This precise parameter modulation allows selective control of Treg suppressor activity, enhancing it for autoimmune disease control while preserving the functional capacity of other immune cells to respond to tumors.

Inventive Principle:

Principle #35Parameter changes

Data Source

PatentUS20240150755A1Modulating regulatory t cell function in autoimmune disease and cancer

Publication Date: 2024.05.09 SALK INST FOR BIOLOGICAL STUDIES

AI summary

Methods of modulating regulatory T (Treg) suppressor activity are provided. Also provided are methods of treating autoimmune diseases and methods of treating cancer. The methods include increasing or reducing the expression or activity of bromodomain-containing 9 (Brd9), bromodomain-containing 7 (Brd7), and/or polybromo 1 (Pbrm1) in a Treg cell or in a subject.