LXRβ Agonist MDSC Reduction Immunotherapy Efficacy

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Solution Overview

Problem

High levels of myeloid-derived suppressor cells (MDSCs) hinder the effectiveness of immunotherapies for cancer by suppressing T-cell functions, leading to poor treatment responses and increased cancer progression.

Innovation Solution

Administering an LXRβ agonist to reduce MDSC levels, potentially in combination with immunotherapies like anti-PD1 or anti-PDL1 antibodies, to enhance the immune system's ability to combat cancer.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Reliability

If immunotherapy is administered to treat cancer, then the immune system is activated to combat cancer, but the presence of high levels of MDSCs suppresses T-cell functions and reduces treatment effectiveness

Engineering Contradiction:

Improveeffectiveness of immunotherapyVSAvoidsuppression of T-cell functions by MDSCs

Core Design Contradiction:

ReliabilityVSObject-affected harmful factors

Solution Approach 1:

The patent targets and eliminates the harmful MDSCs that suppress immune function, thereby converting the suppressed immune state into an activated anti-cancer immune response. By selectively reducing MDSC populations through LXRβ agonist treatment, the harmful suppression is removed and the immune system's anti-cancer capabilities are restored and enhanced.

Inventive Principle:

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

Solution Approach 2:

The patent changes the population parameter of MDSCs by administering LXRβ agonists, which specifically reduce MDSC levels while preserving or enhancing T-cell populations. This parameter change in the immune cell composition transforms the immune microenvironment from a suppressed state to an activated state, improving immunotherapy effectiveness.

Inventive Principle:

Principle #35Parameter changes

2Productivity

If MDSC levels are high in cancer patients, then the immune system is suppressed and treatment response decreases, but reducing MDSC levels is needed to improve immunotherapy response

Engineering Contradiction:

Improveresponse rate to immunotherapyVSAvoidlevels of MDSCs

Core Design Contradiction:

ProductivityVSQuantity of substance

Solution Approach 1:

The patent extracts and removes the harmful MDSC component from the immune system through LXRβ agonist treatment. By selectively depleting MDSC populations without broadly suppressing the immune system, the treatment isolates and eliminates the specific cell type responsible for immunosuppression, thereby improving immunotherapy response rates.

Inventive Principle:

Principle #2Taking out (Extraction)

3Reliability

If LXRβ agonist is administered to reduce MDSC levels, then immune response against cancer is improved, but the mechanism by which LXRβ agonist selectively targets MDSCs needs to be understood

Engineering Contradiction:

Improveimmune response effectivenessVSAvoidcomplexity of selective targeting mechanism

Core Design Contradiction:

ReliabilityVSDevice complexity

Solution Approach 1:

The LXRβ agonist acts as an intermediary molecule that selectively binds to and modulates LXRβ receptors expressed on MDSCs. This intermediary approach allows selective targeting of MDSCs through receptor-specific binding, triggering intracellular signaling pathways that reduce MDSC survival and function while sparing other immune cell populations.

Inventive Principle:

Principle #24Intermediary (Mediator)

Data Source

PatentUS11648220B2Methods for the treatment of myeloid derived suppressor cells related disorders

Publication Date: 2023.05.16 THE ROCKEFELLER UNIV

AI summary

The invention features methods of treating disorders related to increased levels of myeloid derived suppressor cells such as cancer or infections. The disclosure also provides methods of treating cancer including combinations of LXRβ agonists and immunotherapies such as PD1 inhibitors, PDL1 inhibitors, and adoptive T-cell transfer therapy.