On-Column T Cell Transduction for Faster Cell Therapy Production
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Solution Overview
Problem
Existing methods for generating genetically engineered T cells for cell therapy are time-consuming and require additional steps or reagents to detach cells from chromatography columns.
Innovation Solution
A method involving on-column transduction of T cells using a chromatography column with a stationary phase that binds to a selection marker on T cells, combined with a T cell stimulatory reagent and viral vector, allowing for T cell transduction within 24 hours without additional detachment steps.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Reliability
If additional steps or reagents are used to detach cells from chromatography columns, then cell recovery is improved, but process time increases
Solution Approach 1:
The T cells spontaneously detach from the stationary phase after transduction without requiring additional reagents or steps. The transduction process itself facilitates cell release, making the system self-serving and eliminating the need for separate detachment procedures.
Solution Approach 2:
The patent combines the transduction process with the cell detachment process into a single integrated operation. By performing on-column transduction, the cells are both transduced and released from the column simultaneously, merging two previously separate steps into one.
2Measurement precision
If T cells are immobilized on chromatography column for selection, then selection efficiency is improved, but additional detachment steps are required
Solution Approach 1:
The patent extracts the detachment requirement from the overall process by designing a system where cells naturally release from the stationary phase after transduction. This removes the need for separate detachment steps and reduces process complexity while maintaining selection efficiency.
Solution Approach 2:
The T cells themselves facilitate their own release from the column through the transduction process. The biological activity of transduction causes structural changes in the cells that lead to spontaneous detachment, making the system self-service and reducing external intervention requirements.
3Manufacturing precision
If multiple separate steps are used for cell selection, stimulation, and transduction, then each step can be optimized, but overall process time increases
Solution Approach 1:
The patent merges cell selection, stimulation, and transduction into a single integrated on-column process. All three operations occur simultaneously while cells are immobilized on the chromatography column, eliminating the sequential execution of separate steps and reducing overall process time.
Solution Approach 2:
The patent maintains continuous useful action by performing selection, stimulation, and transduction in an uninterrupted sequence within the same operational framework. The process flows continuously from cell binding to transduction to release without intermediate stopping or transfer steps.
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
This method significantly reduces the time required to generate transduced T cells by immobilizing and stimulating them on the column, facilitating efficient production of genetically engineered T cells for cell therapy.
Implementation Method 1
the stationary phase comprises a selection agent that specifically binds to a selection marker expressed on the surface of the plurality of T cells, wherein specific binding of the selection agent to the selection marker effects the immobilization of the plurality of T cells on the stationary phase
Data Source
AI summary
Provided herein are methods for selecting, stimulating, and transducing cells in a sample using column chromatography, and collecting and/or eluting the cells from the column without using additional steps or reagents to facilitate detachment of the cells from the column. In some aspects, the methods provided herein reduce the time needed to generate a population of selected, stimulated, and transduced cells useful for, ultimately, cell therapy, compared to existing methods. Also provided are articles of manufacture and apparatus thereof.