Closed-System Immune Cell Transduction and Expansion
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Solution Overview
Problem
Current methods for modifying and expanding immune cells for adoptive cell therapy are complex, labor-intensive, costly, and limited in accessibility, making them difficult to deploy widely for cancer treatment, especially for patients who cannot afford or travel to specialized facilities.
Innovation Solution
A method for transducing and expanding T cells and NK cells in a closed system using recombinant retroviruses or lentiviral particles, which includes activating, transducing, and expanding cells within the same chamber without washing, allowing for simpler and more cost-effective production of genetically modified cells.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Reliability
If traditional methods for modifying and expanding immune cells are used, then therapeutic effectiveness can be achieved, but the process becomes complex, labor-intensive, and costly
Solution Approach 1:
The patent combines multiple separate steps (activation, transduction, expansion) into a single integrated closed system process. Cells are activated and transduced simultaneously in the same chamber without intermediate washing steps, merging what were previously distinct operational phases into one continuous process that reduces complexity while maintaining therapeutic effectiveness
Solution Approach 2:
The closed system chamber serves multiple functions simultaneously: it acts as both the activation chamber and transduction chamber, eliminating the need for separate specialized equipment for each step. This multi-functional approach reduces device complexity while preserving the therapeutic outcome
2Reliability
If traditional multi-step methods with washing are used, then cell modification can be achieved, but contamination risks increase and costs rise
Solution Approach 1:
The process maintains continuous operation within the closed system without interrupting for washing steps between activation and transduction. This continuous action eliminates exposure to external environment that would occur during opening and closing of chambers for washing, thereby reducing contamination risk while maintaining cell modification effectiveness
Solution Approach 2:
The closed system chamber acts as an intermediary barrier that protects cells from external contamination during the transition from activation to transduction. By keeping cells enclosed and using sealed connections for reagent addition, the chamber mediates between the need for process steps and the need to prevent contamination
3Manufacturing precision
If specialized ex vivo manufacturing facilities are used, then high-quality cell therapy can be produced, but accessibility and cost-effectiveness decrease
Solution Approach 1:
The patent segments the complex manufacturing process into a simplified modular closed system that can be operated with fewer specialized skills. By dividing the process into discrete, well-defined steps within the closed system (activation/transduction followed by expansion), it reduces the need for highly specialized facilities while maintaining quality standards
Solution Approach 2:
The closed system uses disposable components and single-use chambers that eliminate the need for complex sterilization and validation infrastructure required in traditional specialized facilities. This approach maintains manufacturing precision while reducing the need for expensive, highly specialized ex vivo manufacturing facilities, thereby improving accessibility
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 approach simplifies the process, reduces contamination risks, and enables the production of large numbers of genetically modified cells from a small blood sample, making adoptive cell therapy more accessible and cost-effective, thereby expanding its deployment beyond specialized facilities.
Implementation Method 1
transducing the T cells and/or NK cells with recombinant retroviruses or recombinant retroviral particles (typically replication incompetent recombinant retroviral particles and in illustrative embodiments replication incompetent lentiviral particles)
Data Source
AI summary
The present disclosure provides methods for genetically modifying and expanding immune cells ex vivo, especially for use in cell-based adoptive immunotherapy. As such, method embodiments are provided for transducing immune cells (e.g. T cells and/or NK cells) that include a step of activating the cells and genetically modifying the activated cells, for example by transducing the cells with recombinant retroviral particles, such as lentiviral particles. Genetically modified cells produced by these methods are also provided. Such methods are typically performed within a closed system, and in illustrative embodiments within a single chamber of a closed system. The methods typically include expanding the genetically modified immune cells in cell expansion media within the closed system, in illustrative embodiments within the single chamber of the closed system. As such, provided herein in illustrative embodiments, are fed-batch, single-reactor method systems.