MDSC Differentiation via TLR Agonists and IL-6

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Solution Overview

Problem

Current methods for producing myeloid-derived suppressor cells (MDSCs) and dendritic cells face challenges in inducing effective anti-cancer immunity due to low immunogenicity of tumor cells and immunosuppressive substances, limiting their therapeutic efficacy in cancer treatment.

Innovation Solution

A method involving the use of toll-like receptor agonists, such as TLR2, TLR4, TLR7, and TLR9 agonists, combined with interleukin 6, to induce differentiation of bone marrow cells into tolerogenic MDSCs and subsequently into immunogenic dendritic cells, which can enhance anti-tumor immunity by promoting Th1 cell differentiation.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Reliability

If conventional methods are used to produce MDSCs and dendritic cells, then cell production is achieved, but the immunogenicity is low and therapeutic efficacy is limited

Engineering Contradiction:

Improvetherapeutic efficacyVSAvoidlow immunogenicity

Core Design Contradiction:

ReliabilityVSObject-generated harmful factors

Solution Approach 1:

The patent applies parameter changes by modifying the differentiation conditions through specific cytokine combinations (GM-CSF, IL-4, IL-10) and Toll-like receptor agonists (LPS, CpG) to transform bone marrow cells into dendritic cells with enhanced immunogenic properties. This changes the cellular parameters including surface marker expression (CD11c, CD86, MHC class II) and cytokine production capacity, thereby improving therapeutic efficacy while maintaining cell production

Inventive Principle:

Principle #35Parameter changes

2Adaptability or versatility

If tumor cells are used directly for immune induction, then anti-tumor immunity is targeted, but the immunogenicity of tumor cells is low

Engineering Contradiction:

Improveanti-tumor immunity inductionVSAvoidlow immunogenicity of tumor cells

Core Design Contradiction:

Adaptability or versatilityVSObject-generated harmful factors

Solution Approach 1:

The patent uses dendritic cells as an intermediary between the tumor antigen and the immune system. Instead of directly using tumor cells which have low immunogenicity, the patent differentiates bone marrow cells into dendritic cells that can efficiently process and present tumor antigens, thereby mediating effective anti-tumor immune responses. The dendritic cells act as a bridge that overcomes the low immunogenicity limitation of direct tumor cell use

Inventive Principle:

Principle #24Intermediary (Mediator)

3Quantity of substance

If immunosuppressive substances are present, then MDSCs are increased, but T cell activity is inhibited

Engineering Contradiction:

ImproveMDSC populationVSAvoidT cell inhibition

Core Design Contradiction:

Quantity of substanceVSObject-generated harmful factors

Solution Approach 1:

The patent converts the immunosuppressive function of MDSCs into a beneficial effect by using dendritic cells to modulate the immune environment. The differentiated dendritic cells produce anti-inflammatory cytokines (IL-10, TGF-β) that suppress excessive immune responses and prevent autoimmune reactions, while simultaneously maintaining anti-tumor immunity. This transforms the potential harm of immune suppression into a beneficial regulatory function

Inventive Principle:

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

Data Source

PatentUS11806364B2Method for producing myeloid-derived suppressor cells, myeloid-derived suppressor cells produced thereby, and methods thereof

Publication Date: 2023.11.07 IND ACADEMIC COOP FOUND YONSEI UNIV

AI summary

The present invention relates to a method for inducing differentiation of bone marrow cells into myeloid-derived suppressor cells (MDSCs) by treating the bone marrow cells with a toll-like receptor agonist (TLR agonist) or type I interferon, or for inducing dendritic cells from the MDSCs.