Human Phagocytic Cell Expansion Through MAFB/MAF Deletion

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Solution Overview

Problem

Existing methods struggle to provide large numbers of non-tumorigenic human phagocytic cells, such as macrophages and dendritic cells, capable of ex vivo proliferation, limiting therapeutic applications like CAR-M therapy.

Innovation Solution

Generate human phagocytic cells with deletions in both MAFB and MAF genes to enhance proliferation potential, allowing for significant expansion in culture.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Quantity of substance

If human phagocytic cells are cultured ex vivo to obtain large numbers of cells for therapy, then the cell quantity increases, but the cells lose their non-tumorigenic character and differentiate capacity

Engineering Contradiction:

Improvecell numberVSAvoidnon-tumorigenic character

Core Design Contradiction:

Quantity of substanceVSReliability

Solution Approach 1:

The patent applies parameter changes by modifying the genetic state of the cells through deletion of MAFB and MAF genes, which fundamentally alters the cellular parameters to enable ex vivo proliferation while maintaining non-tumorigenic character and differentiation capacity

Inventive Principle:

Principle #35Parameter changes

Solution Approach 2:

The patent extracts the problematic regulatory elements (MAFB and MAF genes) that prevent proliferation, thereby removing the obstacle to cell expansion while preserving the essential functional characteristics of phagocytic cells

Inventive Principle:

Principle #2Taking out (Extraction)

2Productivity

If human phagocytic cells are expanded in culture to achieve sufficient cell numbers, then productivity increases, but the cells fail to maintain their differentiated state and functional capacity

Engineering Contradiction:

Improvecell expansion capacityVSAvoiddifferentiated state

Core Design Contradiction:

ProductivityVSStability of the object's composition

Solution Approach 1:

The patent changes the genetic parameters by deleting MAFB and MAF genes, which enables the cells to maintain their differentiated state while acquiring the capacity for ex vivo expansion, thereby resolving the contradiction between productivity and compositional stability

Inventive Principle:

Principle #35Parameter changes

3Ease of manufacture

If conventional culture methods are used to propagate phagocytic cells, then the process is simple and reliable, but the cell yield is insufficient for therapeutic applications

Engineering Contradiction:

Improveculture method simplicityVSAvoidcell yield

Core Design Contradiction:

Ease of manufactureVSQuantity of substance

Solution Approach 1:

The patent applies parameter changes through genetic modification (deletion of MAFB and MAF genes) that transforms the cellular proliferation parameters, enabling high cell yield while maintaining the simplicity and reliability of culture methods

Inventive Principle:

Principle #35Parameter changes

Data Source

PatentUS20250283042A1Ex-VIVO proliferation of human phagocytic cells

Publication Date: 2025.09.11 TECHNISCHE UNIVERSITAT DRESDEN

AI summary

The invention provides human phagocytic cells which are not tumorigenic, yet still capable of cell division ex-vivo, such as in cell culture. A culture containing these cells can be expanded manyfold, that is the cell number in such a culture can be increased by a factor of 10 or more. The cells show characteristics of functional phagocytes in a differentiated state and are capable to alleviate pathological defects in in vivo models.