IL-23R Antagonists Reprogram Intratumoral Treg Cells

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Solution Overview

Problem

Regulatory T cells (Treg cells) can impede anti-tumor immune responses and promote cancer growth by exerting immune suppression, which existing immunotherapies have struggled to effectively address.

Innovation Solution

The selective induction of Treg cell phenotypic instability and the conversion of intratumoral Treg cells into T effector cells (Teff cells) by inhibiting the IL-23R cytokine receptor subunit, using agents such as polypeptides, nucleic acids, or small molecules that specifically target IL-23R without affecting IL-12Rβ activity.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Reliability

If Treg cells are depleted or blocked to enhance anti-tumor immune responses, then cancer treatment efficacy is improved, but systemic immune suppression is reduced which may cause autoimmune side effects

Engineering Contradiction:

Improvecancer treatment efficacyVSAvoidautoimmune side effects

Core Design Contradiction:

ReliabilityVSObject-affected harmful factors

Solution Approach 1:

The patent applies local quality by using an antibody (anti-IL-23R) that selectively targets and depletes Treg cells within the tumor microenvironment while preserving systemic Treg cells. This spatially differentiated approach allows immune suppression to be locally overcome in the tumor site while maintaining systemic immune homeostasis, thereby improving cancer treatment efficacy without causing autoimmune side effects

Inventive Principle:

Principle #3Local quality

Solution Approach 2:

The patent segments the Treg cell population into intratumoral and systemic compartments, applying different treatment effects to each. The anti-IL-23R antibody specifically depletes intratumoral Treg cells that mediate immune suppression in the tumor microenvironment, while systemic Treg cells remain intact to prevent autoimmune reactions. This segmentation allows simultaneous improvement of anti-tumor immunity and prevention of autoimmune side effects

Inventive Principle:

Principle #1Segmentation

2Reliability

If existing immunotherapies deplete Treg cells systemically, then anti-tumor immune responses are enhanced, but the complexity of treatment protocols increases

Engineering Contradiction:

Improveanti-tumor immune responseVSAvoidtreatment protocol complexity

Core Design Contradiction:

ReliabilityVSDevice complexity

Solution Approach 1:

The patent extracts the harmful function of Treg cells specifically from the tumor microenvironment by using an antibody that targets IL-23R expressed on intratumoral Treg cells. This extraction approach removes the immune suppression mechanism locally at the tumor site while leaving systemic Treg cells intact, thereby enhancing anti-tumor immune responses without requiring complex combination therapies or protocols

Inventive Principle:

Principle #2Taking out (Extraction)

Data Source

PatentUS12202904B2IL-23R antagonists to reprogram intratumoral T regulatory cells into effector cells

Publication Date: 2025.01.21 DANA FARBER CANCER INSTITUTE INC

AI summary

Provided by the disclosure are compositions and methods for modulating differentiation of regulatory T cells. In some embodiments, methods include selectively decreasing IL-23R activity and/or IL-23R expression without significantly decreasing IL-12Rβ activity and/or IL-12Rβ expression.