Gene-Modified T Cell Production via CD3 Activator and RetroNectin Beads

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Solution Overview

Problem

Current methods for producing gene-modified T cells are inefficient and costly, particularly in maintaining the undifferentiated state of T cells, which affects the duration and effectiveness of the treatment.

Innovation Solution

A method involving the treatment of a cell population containing T cells with a CD3 signal activator, followed by contact with beads bound with a virus containing the target gene, to efficiently introduce the gene into the T cells while maintaining their undifferentiated state.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Duration of action of moving object

If conventional gene introduction methods are used for T cells, then gene modification can be achieved, but the T cells lose their undifferentiated state and function duration is reduced

Engineering Contradiction:
Improveduration of T cell functionVSAvoidmaintenance of undifferentiated state
Core Design Contradiction:
Duration of action of moving objectVSReliability

Solution Approach 1:

The T cells are pre-activated with anti-CD3/anti-CD28 antibodies before virus introduction. This preliminary activation prepares the cells for more efficient gene uptake while maintaining their undifferentiated state, resolving the contradiction between gene introduction effectiveness and preservation of T cell functionality.

Inventive Principle:
Principle #10Preliminary action

Solution Approach 2:

RetroNectin-coated beads serve as an intermediary carrier that binds both the retrovirus and the T cells. This intermediary facilitates efficient gene transfer while the pre-activation with antibodies ensures the cells remain in an undifferentiated state, thus maintaining both transfer efficiency and cell functionality.

Inventive Principle:
Principle #24Intermediary (Mediator)

2Productivity

If conventional gene introduction methods are used, then gene modification is achieved, but production efficiency is low and costs are high

Engineering Contradiction:
Improveproduction efficiency of gene-modified T cellsVSAvoidtime for T cell culture and gene introduction
Core Design Contradiction:
ProductivityVSLoss of time

Solution Approach 1:

The use of RetroNectin-coated magnetic beads as an intermediary significantly accelerates the gene introduction process compared to conventional methods. The beads enable rapid binding and transfer of retrovirus to T cells, reducing culture time and improving production efficiency without compromising cell quality.

Inventive Principle:
Principle #24Intermediary (Mediator)

Solution Approach 2:

The invention changes the physical and chemical parameters of the gene introduction process by using RetroNectin coating and magnetic bead technology. These parameter changes enable faster and more efficient gene transfer, reducing the time required for producing gene-modified T cells while maintaining high production quality.

Inventive Principle:
Principle #35Parameter changes

Data Source

PatentUS20250122472A1Method for producing gene-modified t cell population
Publication Date: 2025.04.17 JSR CORPORATION
  • US20250122472A1 patent drawing
  • US20250122472A1 patent drawing
  • US20250122472A1 patent drawing

AI summary

Provided is a method of producing a gene-modified T cell population, including mixing a cell population containing T cells with beads each having bound thereto a virus containing a target gene to introduce the target gene into each of the cells of the cell population, wherein the cell population containing the T cells is cultured in a solution containing a CD3 signal activator that is present without being immobilized on a solid phase.