Multimerization Reagent for T Cell Expansion and Chromatography Separation
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Solution Overview
Problem
Existing methods for expanding T cell populations, such as those using magnetic beads like Dynabeads, are difficult to integrate into clinical trials due to the need for complete removal of beads before administration, and lack compatibility with automated processes required for therapeutic applications.
Innovation Solution
A method involving a multimerization reagent with reversibly immobilized agents that provide primary and accessory activation signals to T cells, allowing for controlled expansion and easy removal of stimulating agents, using a soluble form or immobilized on a solid support, facilitating chromatography-based separation and automated processes.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Productivity
If magnetic beads like Dynabeads are used for T cell expansion, then T cell proliferation is achieved, but complete removal of beads before administration is difficult and time-consuming
Solution Approach 1:
The invention extracts the stimulating agents (antibodies and multimerization reagent) from the expansion system, allowing them to be removed via chromatography while leaving the expanded T cells ready for administration. This resolves the contradiction by separating the expansion function from the administration readiness requirement.
Solution Approach 2:
The invention introduces a multimerization reagent as an intermediary that temporarily mediates the stimulation of T cells during expansion, then allows for complete removal of this intermediary through chromatography, enabling both efficient expansion and administration readiness.
2Productivity
If magnetic beads are used for T cell expansion, then cell proliferation is achieved, but compatibility with automated therapeutic processes is lacking
Solution Approach 1:
The invention replaces the mechanical magnetic bead system with a biochemical system using soluble multimerization reagents and chromatography-based separation, which is inherently more compatible with automated liquid handling and therapeutic manufacturing processes.
3Productivity
If stimulating agents are used for T cell expansion, then cell activation and proliferation occur, but complete removal of agents is required before administration
Solution Approach 1:
The invention utilizes parameter changes in chromatography conditions to selectively retain stimulating agents while allowing expanded T cells to pass through, achieving complete agent removal through controlled changes in binding affinity and flow conditions.
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
Enables efficient and controlled expansion of T cell populations, ensuring the removal of stimulating agents and compatibility with automated therapeutic processes, enhancing the suitability for clinical applications.
Implementation Method 1
a multimerization reagent that has reversibly immobilized thereon a first agent that provides a primary activation signal to the cells
Implementation Method 2
the first agent binds to a receptor molecule on the surface of the cells, thereby providing a primary activation signal to the cells
Implementation Method 3
the second agent binds to the accessory molecule on the surface on the surface of the cells, thereby stimulating the activated cells to expand
Implementation Method 4
the reagents necessary for the expansion are then removed by chromatography on a suitable stationary phase
Data Source
AI summary
The present invention relates to in vitro-methods of expanding a population of cells such as lymphocytes, comprising contacting a sample comprising a population of cells with a multimerization reagent. The multimerization reagent has reversibly immobilized thereon (bound thereto) a first agent that provides a primary activation signal to the cells and optionally, a second agent that provides a co-stimulatory signal. The invention also provides multimerization reagents, kits, arrangements and an apparatus for expanding cells.