TIL Expansion Bioreactor with Sieve Segmentation
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Solution Overview
Problem
Current TIL manufacturing processes are limited by length, cost, and sterility concerns, necessitating improved cost-effectiveness, scalability, and potency of TIL preparations for cancer treatment.
Innovation Solution
A tissue culture device with a gas permeable surface and a sieve that separates compartments, allowing for minimal human intervention and automated/semi-automated TIL expansion, featuring a method that includes priming and rapid expansions without opening the device, using IL-2 and OKT-3 with antigen presenting cells to enhance TIL populations.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Reliability
If traditional TIL manufacturing processes are used, then manual operation flexibility is maintained, but sterility is compromised and contamination risk increases
Solution Approach 1:
The manufacturing process is segmented into distinct modular stages (priming expansion in first compartment, rapid expansion in second compartment) separated by a sieve. Each compartment can be independently managed and processed, enabling automated operations while maintaining sterility barriers between stages.
Solution Approach 2:
The sieve acts as an intermediary structure between the two compartments, allowing automated transfer of TILs from the priming compartment to the rapid expansion compartment without direct human intervention. This intermediary enables sterile, automated processing while maintaining process control.
2Object-affected harmful factors
If traditional open manufacturing processes are used, then process monitoring is easier, but microbial contamination risk increases
Solution Approach 1:
The closed bioreactor system creates a controlled, sterile environment that protects TILs from microbial contamination throughout the manufacturing process. The sealed compartments with defined access ports maintain an inert, contamination-free atmosphere while enabling automated operations.
3Productivity
If manual TIL processing is used, then flexibility in handling is maintained, but productivity and scalability are limited
Solution Approach 1:
The bioreactor system incorporates dynamic elements including rotatable components that enable automated orientation changes between compartments, and adjustable parameters for controlling TIL expansion rates. This dynamic design enables high-throughput automated processing while maintaining operational flexibility.
4Quantity of substance
If extended manufacturing time is used, then TIL population expansion is improved, but production cost increases
Solution Approach 1:
The two-compartment system enables continuous TIL expansion operations where the priming compartment prepares cells while the rapid expansion compartment simultaneously multiplies them. This continuous process reduces total manufacturing time and costs while achieving high TIL populations, as both compartments operate in parallel rather than sequentially.
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
The solution enables efficient, scalable, and sterile TIL expansion, producing a potent therapeutic population with reduced microbial contamination risk, enhancing treatment efficacy and cost-effectiveness.
Implementation Method 1
a device body having a first gas permeable surface for culturing cells, a second gas permeable surface for culturing cells
Implementation Method 2
a sieve disposed within the device body between the first gas permeable surface and the second gas permeable surface thereby separating the device into: (i) a first compartment... and (ii) a second compartment
Data Source
AI summary
The present invention provides automated methods for expanding TILs and producing therapeutic populations of TILs, including novel tissue culture devices and automated methods for expanding TIL populations in a closed system that lead to improved efficacy, improved phenotype, and increased metabolic health of the TILs in a shorter time period, while allowing for reduced microbial contamination as well as decreased costs.