Closed Bioreactor Bag Process for Autologous T Cell Expansion
Find Innovative SolutionsGenerate Solutions
Solution Overview
Problem
Current methods for producing autologous genetically engineered T cells are labor-intensive, costly, and inefficient, with high donor-to-donor variability, requiring complex and costly manual processes that increase the risk of contamination and facility footprint, making it challenging to achieve clinically relevant quantities and quality.
Innovation Solution
A method utilizing a closed single-use bioreactor bag with rocking motion for culturing, transducing, and expanding autologous T cells, using apheresed donor cells without further isolation or enrichment, and employing soluble T cell activators and cytokines to enhance transduction efficiency and cell growth, resulting in high-purity, high-viability T cells with reduced background activation and target irrelevant toxicity.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Adaptability or versatility
If manual processes are used for producing autologous T cells, then flexibility and customization for each patient is improved, but labor intensity and risk of contamination increase
Solution Approach 1:
The patent employs single-use closed bioreactor bags that are disposed of after one use, eliminating the need for sterilization and cleaning between patients. This disposable approach maintains patient-specific customization while dramatically reducing contamination risk and manual handling requirements.
Solution Approach 2:
The closed bioreactor system creates an isolated, controlled environment for cell culture that protects against external contamination. The system maintains sterility throughout the manufacturing process while allowing flexible processing of patient-specific cells.
2Object-affected harmful factors
If complex automated systems are used for closed process platforms, then contamination risk is reduced, but capital investment and device complexity increase
Solution Approach 1:
The single-use bioreactor bags replace expensive, complex automated closed systems with simple, disposable containers. Each bag is pre-sterilized and ready for use, eliminating the need for complex sterilization systems, cleaning-in-place equipment, and automated handling mechanisms while maintaining closed-process benefits.
Solution Approach 2:
The bioreactor bags are designed to be self-contained units that require minimal external intervention. The bags themselves provide the closed environment and sterility barriers, eliminating the need for complex external control systems, sensors, and automation infrastructure.
3Adaptability or versatility
If multiple manual handling steps are used for cell processing, then flexibility in process adjustments is improved, but time consumption and labor intensity increase
Solution Approach 1:
The patent combines multiple process steps (cell activation, transduction, and expansion) into a single continuous process within one bioreactor bag. This eliminates the need for manual cell transfers between vessels, reducing both time consumption and opportunities for contamination while maintaining the ability to optimize process parameters.
Solution Approach 2:
The continuous rocking motion of the bioreactor bag maintains cell suspension and nutrient distribution throughout the entire culture period without interruption. This continuous action eliminates the need for periodic manual agitation or cell harvesting and re-suspending steps, significantly reducing processing time and labor.
4Productivity
If apheresed donor cells are used without isolation or enrichment, then processing time and complexity are reduced, but cell purity and transduction efficiency may be affected
Solution Approach 1:
The patent uses soluble T cell activators and optimized culture conditions to selectively stimulate and expand the desired T cell populations from the mixed apheresed cell sample. By changing the biochemical parameters (cytokine concentrations, activator types), the system achieves high purity and transduction efficiency without physical separation steps.
Solution Approach 2:
Soluble T cell activators serve as intermediaries that selectively bind to and activate specific T cell surface receptors. This biochemical mediation allows the system to distinguish and preferentially expand target T cell populations from the mixed cell input, achieving purification through selective biological interaction rather than physical separation.
Data Source
AI summary
The present invention relates to a method for enhancing production of autologous genetically engineered T cells for use in cell therapy applications.