Mcoln-1 Modulators Regulate Dendritic Cell Migration

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Solution Overview

Problem

Current cancer immunotherapy and autoimmune disease treatments face challenges in enhancing the migration of dendritic cells (DCs) to lymphoid organs, which is crucial for triggering effective immune responses and preventing metastasis, as existing methods have not successfully inhibited cancer cell migration effectively.

Innovation Solution

Modulating the lysosomal calcium channel Mcoln-1 using activators or inhibitors to regulate DC migration, enhancing or impeding cell migration as needed, thereby improving the efficacy of antitumoral vaccinations and autoimmune disease treatments, and preventing metastasis.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Reliability

If DCs are injected to patients for cancer immunotherapy, then antigen presentation capability is improved, but migration efficiency to lymphoid organs deteriorates

Engineering Contradiction:
Improveantigen presentation capabilityVSAvoidmigration efficiency to lymphoid organs
Core Design Contradiction:
ReliabilityVSSpeed

Solution Approach 1:

The patent modulates the lysosomal calcium channel Mcoln-1 to alter DC migration parameters. By activating Mcoln-1, the patent enhances DC migration speed and persistence to lymphoid organs without compromising antigen presentation capability, resolving the contradiction between reliable antigen presentation and efficient migration.

Inventive Principle:
Principle #35Parameter changes

2Object-affected harmful factors

If Mcoln-1 is inhibited to prevent cancer cell migration, then metastasis is reduced, but DC migration and immune response are impaired

Engineering Contradiction:
Improvecancer cell migration and metastasisVSAvoidDC migration and immune response
Core Design Contradiction:
Object-affected harmful factorsVSReliability

Solution Approach 1:

The patent applies opposite actions to different cell types: Mcoln-1 is activated in DCs to enhance their migration and immune response, while Mcoln-1 is inhibited in cancer cells to prevent their migration and metastasis. This inverted approach allows simultaneous improvement of immune response and reduction of cancer spread.

Inventive Principle:
Principle #13The other way round (Inversion)

Solution Approach 2:

The patent uses Mcoln-1 as a selective target that can be differentially regulated in different cell types through specific modulators. This intermediary approach enables precise control over cell migration - enhancing it in beneficial DCs while blocking it in harmful cancer cells, thereby resolving the contradiction between preventing metastasis and maintaining immune response.

Inventive Principle:
Principle #24Intermediary (Mediator)

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

Mcoln-1 modulation increases DC migration and persistence, enhancing antitumoral immune responses and autoimmune tolerance, while inhibiting cancer cell migration to prevent metastasis, offering a therapeutic target with potential for increased treatment efficacy and reduced toxicity.

Implementation Method 1

Mcoln-1 is a lysosomal calcium channel that controls DC migration

Methodology Applied
Scientific EffectCalcium channel modulation:

Implementation Method 2

lysosomes are tightly apposed to these actin structures in migrating DCs and have a role in the regulation of actin dynamics and DC migration

Methodology Applied
Scientific EffectActin polymerization:

Data Source

PatentEP3105319B1Use of mcoln-1 modulators to regulate cell migration
Publication Date: 2020.03.25 INSTITUT CURIE
  • EP3105319B1 patent drawingFigure 1A~1C
  • EP3105319B1 patent drawingFigure 2A~2D
  • EP3105319B1 patent drawingFigure 3~4B

AI summary

The present invention relates to the use of modulators of Mcoln-1 for modulating the cells migration, in particular the migration of dendritic cells and tumor cells, especially for antitumoral vaccination, autoimmune diseases treatment, and metastasis prevention.