Ibudilast Suppresses MDSCs to Enhance Immune Response

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Solution Overview

Problem

Current treatments for cancer and microorganism infections often face challenges in suppressing myeloid-derived suppressor cells (MDSCs) and reducing immune suppression, which can hinder the effectiveness of immune responses.

Innovation Solution

Administering ibudilast, a small molecule with MIF inhibitory activity, to patients to suppress MDSCs, reduce immune suppression, and increase CD4+ T-cell counts, thereby enhancing immune responses against cancer and microorganism infections.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Reliability

If current treatments for cancer and microorganism infections are used, then treatment is provided, but immune suppression persists and MDSCs are not effectively suppressed

Engineering Contradiction:

Improveeffectiveness of immune responseVSAvoidimmune suppression

Core Design Contradiction:

ReliabilityVSObject-affected harmful factors

Solution Approach 1:

The patent converts the harmful immune suppression caused by MDSCs into a benefit by using ibudilast to specifically suppress MDSCs while preserving or enhancing protective immune responses. The drug transforms the immunosuppressive environment into an immunopromoting one, allowing the immune system to effectively fight cancer and infections.

Inventive Principle:

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

Solution Approach 2:

The patent changes the immunological parameters by administering ibudilast, which alters the balance of immune cell populations. Specifically, it reduces MDSC counts and modifies the functional state of immune cells, thereby changing the overall immune response parameters from suppressed to activated.

Inventive Principle:

Principle #35Parameter changes

2Quantity of substance

If ibudilast is administered to suppress MDSCs, then immune suppression is reduced and CD4+ T-cell counts increase, but the mechanism involves multiple pharmacological activities

Engineering Contradiction:

ImproveCD4+ T-cell countVSAvoidpharmacological mechanism complexity

Core Design Contradiction:

Quantity of substanceVSDevice complexity

Solution Approach 1:

The patent utilizes the multi-functionality of ibudilast, which exhibits multiple pharmacological activities including PDE3/4/10/11 inhibition, MIF inhibition, TLR4 antagonism, and leukotriene D4 antagonism. This single compound performs multiple immunomodulatory functions simultaneously, simplifying the treatment regimen while achieving complex immunological outcomes.

Inventive Principle:

Principle #6Universality (Multi-functionality)

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

Ibudilast effectively reduces MDSC counts and immune suppression, leading to increased CD4+ T-cell counts and improved immune responses, potentially improving treatment outcomes for cancer and infections.

Implementation Method 1

Ibudilast (3-isobutyryl-2-isopropylpyrazolo[1,5-a]pyridine) is an inhibitor of macrophage inhibitory factor (MIF)

Methodology Applied

Scientific EffectMIF inhibition:

Implementation Method 2

is a selective inhibitor of cyclic nucleotide phosphodiesterases (PDEs) 3A, 4, 10A1 and 11A1

Methodology Applied

Scientific EffectPhosphodiesterase inhibition:

Implementation Method 3

Ibudilast also acts as a leukotriene D4 antagonist, an anti-inflammatory

Methodology Applied

Scientific EffectLeukotriene D4 antagonism:

Implementation Method 4

has toll-like receptor-4 (TLR4) antagonistic activity

Methodology Applied

Scientific EffectTLR4 antagonism:

Data Source

PatentEP3740205B1Methods of suppressing myeloid-derived suppressor cells in patients

Publication Date: 2023.09.20 MEDICINOVA INC

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AI summary

Methods of suppressing myeloid-derived suppressor cells (MDSCs), reducing immune suppression, reducing regulatory T-cell count and increasing CD4+ T-cell count in cancer patients using ibudilast.