IL-18 Modulation of Regulatory T Cells for Selective Depletion

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Solution Overview

Problem

Current methods for treating cancer and other diseases involving regulatory T cells (Tregs) are inadequate, as they either fail to selectively deplete Tregs or cause significant side effects, such as bone marrow suppression and neurotoxicity.

Innovation Solution

Administration of interleukin-18 (IL-18) to selectively deplete CD4+CD25+FoxP3+ Tregs, thereby increasing the number of CD8+ effector T cells, which enhances anti-tumor immune responses and reduces Treg-mediated immune suppression.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Quantity of substance

If current methods (DAB389IL-2, fludarabine) are used to eliminate Tregs, then Treg depletion is achieved, but significant side effects occur (bone marrow suppression, neurotoxicity, loss of activated T cells)

Engineering Contradiction:

ImproveTreg depletionVSAvoidside effects

Core Design Contradiction:

Quantity of substanceVSObject-affected harmful factors

Solution Approach 1:

The patent changes the parameter of Treg-specificity by using IL-18, which selectively targets CD4+CD25+FoxP3+ Tregs without affecting other T cell populations. This parameter change in selectivity resolves the contradiction by achieving Treg depletion without the broad-spectrum toxicity of existing methods.

Inventive Principle:

Principle #35Parameter changes

Solution Approach 2:

The patent extracts the harmful side effects by identifying and eliminating non-specific toxicity through IL-18's selective mechanism. IL-18 specifically targets Tregs while leaving activated T cells and bone marrow cells intact, thereby extracting the harmful effects associated with non-selective methods.

Inventive Principle:

Principle #2Taking out (Extraction)

2Quantity of substance

If DAB389IL-2 is used to eliminate Tregs, then Treg depletion is achieved, but activated T cells are also removed, limiting use after vaccination

Engineering Contradiction:

ImproveTreg depletionVSAvoidtiming flexibility

Core Design Contradiction:

Quantity of substanceVSAdaptability or versatility

Solution Approach 1:

The patent applies local quality by making the treatment effect specific to Tregs rather than all T cells. IL-18 selectively depletes Tregs while preserving activated T cells, enabling flexible timing of treatment both before and after vaccination without compromising anti-tumor immunity.

Inventive Principle:

Principle #3Local quality

3Quantity of substance

If fludarabine is used to block Tregs, then Treg suppression is achieved, but bone marrow cells and neurotoxicity are caused

Engineering Contradiction:

ImproveTreg suppressionVSAvoidbone marrow suppression and neurotoxicity

Core Design Contradiction:

Quantity of substanceVSObject-generated harmful factors

Solution Approach 1:

The patent converts the potential harm of Treg depletion methods into a benefit by using IL-18, which achieves Treg suppression without causing bone marrow suppression or neurotoxicity. The selective mechanism transforms a potentially harmful broad-spectrum treatment into a safe, targeted therapy.

Inventive Principle:

Principle #22Blessing in disguise (Convert harm into benefit)

4Quantity of substance

If Tregs are increased in tumor samples, then immune suppression is enhanced, but anti-tumor immune response is inhibited

Engineering Contradiction:

ImproveTreg numberVSAvoidanti-tumor immune response

Core Design Contradiction:

Quantity of substanceVSReliability

Solution Approach 1:

The patent applies inversion by targeting and depleting Tregs instead of enhancing them. By using IL-18 to reduce Treg numbers and shift the T cell balance toward CD8+ effector T cells, the patent inverts the natural tumor-associated Treg expansion into a therapeutic advantage, thereby enhancing anti-tumor immunity.

Inventive Principle:

Principle #13The other way round (Inversion)

Data Source

PatentUS8679471B2Modulation of regulatory T cells by human IL-18

Publication Date: 2014.03.25 THE TRUSTEES OF THE UNIV OF PENNSYLVANIA

AI summary

The present invention relates to compositions and methods for modulating the presence and/or activity of regulatory T cells in a subject.