CD11b Low Macrophage Conditioned Medium for Dormant Tumor Cell Elimination

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Solution Overview

Problem

Current cancer therapies are limited in effectively targeting dormant, non-proliferating tumor cells and metastatic progression, as they primarily target actively dividing cells, and existing treatments for fibrosis lack the ability to cure the condition, with severe side effects and limited efficacy.

Innovation Solution

The use of conditioned cell culture medium from CD11b low macrophages, which are characterized by reduced CD11b expression, to induce cell death in malignant cells and inhibit fibrosis by inhibiting the transition of fibroblasts into myofibroblasts and reducing Type I collagen secretion and α-SMA expression.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Reliability

If conventional chemotherapeutic agents are used to treat cancer, then actively dividing tumor cells are targeted, but dormant, non-proliferating tumor cells are not eradicated leading to disease recurrence

Engineering Contradiction:
Improvecancer treatment efficacyVSAvoidability to target different tumor cell states
Core Design Contradiction:
ReliabilityVSAdaptability or versatility

Solution Approach 1:

The patent changes the functional parameter of macrophages by inducing a specific phenotype (CD11b low expression) through exposure to apoptotic cells and cytokines. This parameter change enables the macrophages to produce conditioned media with unique properties that can target dormant tumor cells, thereby expanding the versatility of cancer treatment to address different tumor cell states.

Inventive Principle:
Principle #35Parameter changes

Solution Approach 2:

The patent introduces conditioned media from CD11b low macrophages as an intermediary substance that mediates the effect on dormant tumor cells. This conditioned media contains bioactive molecules that serve as intermediaries to transmit the anti-tumor effect specifically to dormant cells without affecting actively dividing cells, thus resolving the contradiction in targeting different cell states.

Inventive Principle:
Principle #24Intermediary (Mediator)

2Reliability

If chemotherapeutic agents are used to treat cancer, then tumor cell proliferation is inhibited, but severe side effects occur including bone marrow suppression, nausea, and ulcerations

Engineering Contradiction:
Improvetumor cell controlVSAvoidside effects on healthy tissues
Core Design Contradiction:
ReliabilityVSObject-affected harmful factors

Solution Approach 1:

The patent applies local quality by creating a specialized macrophage population with distinct functional properties (CD11b low expression) that produces conditioned media with specific bioactive molecules. This localized functional differentiation enables selective action on dormant tumor cells while sparing healthy tissues, thereby reducing side effects while maintaining tumor control efficacy.

Inventive Principle:
Principle #3Local quality

Solution Approach 2:

Instead of using direct chemotherapeutic agents that kill dividing cells, the patent inverts the approach by using conditioned media from specially activated macrophages to induce cell death in dormant cells through indirect mechanisms. This inversion allows for more selective targeting with reduced harm to healthy tissues.

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

3Reliability

If fibroblasts transition into myofibroblasts during wound healing, then tissue repair is promoted, but excessive fibrosis and scarring occur

Engineering Contradiction:
Improvetissue repair efficiencyVSAvoidfibrosis and scarring
Core Design Contradiction:
ReliabilityVSObject-generated harmful factors

Solution Approach 1:

The patent employs feedback control by using conditioned media from CD11b low macrophages that contains regulatory molecules capable of monitoring and modulating the fibroblast-to-myofibroblast transition. The conditioned media provides negative feedback to prevent excessive myofibroblast differentiation, thereby maintaining tissue repair efficiency while preventing pathological fibrosis.

Inventive Principle:
Principle #23Feedback

Solution Approach 2:

The patent changes the functional parameters of macrophages to produce conditioned media with specific anti-fibrotic properties. This parameter change in macrophage phenotype enables the conditioned media to regulate the fibroblast-myofibroblast transition, balancing tissue repair needs with prevention of excessive scarring.

Inventive Principle:
Principle #35Parameter changes

Data Source

PatentEP2941256B1CD11b- low macrophages and conditioned media thereof for treating cancer and/or fibrosis
Publication Date: 2020.05.06 CARMEL HAIFA UNIV ECONOMIC
  • EP2941256B1 patent drawingFigure 1A
  • EP2941256B1 patent drawingFigure 1B~2A
  • EP2941256B1 patent drawingFigure 2B~2C

AI summary

A conditioned medium of CD11blow macrophages and methods for preparing it are provided. Pharmaceutical compositions comprising the CD11blow macrophages conditioned medium or a culture of CD11blow macrophages and their use in the treatment of cancer or fibrosis are also provided.