Semi-Automatic TIL Processing Device for Cell Viability
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Solution Overview
Problem
Current methods for isolating and processing tumor-infiltrating lymphocytes (TILs) from resected tumors are labor-intensive, require strict environmental conditions, and often result in cell deterioration due to oxygen deficiency and improper handling, leading to suboptimal viability and diversity of the final cellular product.
Innovation Solution
A semi-automatic aseptic tissue processing method and device that involves cryopreservation and expansion of TILs using IL-2, CD3 agonists, and antigen-presenting cells, with controlled disaggregation and enrichment to produce therapeutic populations of TILs, enhancing cell viability and diversity.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Productivity
If manual tissue processing methods are used to isolate TILs, then flexibility and adaptability are maintained, but labor intensity increases and processing time is excessive
Solution Approach 1:
The tissue processing system is divided into distinct functional modules: a disaggregation module for mechanical and enzymatic tissue breakdown, an enrichment module for cell separation and concentration, and a stabilization module for cell preservation. Each module performs a specific function in the TIL isolation workflow, enabling automated high-throughput processing while maintaining manageable system complexity through functional segmentation.
2Reliability
If strict environmental conditions are maintained during TIL processing, then cell viability is improved, but ease of operation decreases due to complex environmental controls
Solution Approach 1:
The stabilization module provides an oxygen-excluded environment for TIL processing and storage, creating an inert atmosphere that prevents oxidative damage to the cells. This controlled environment maintains high cell viability and preserves tumor microenvironment characteristics without requiring complex environmental control systems, as the oxygen exclusion is achieved through the design of the stabilization module itself.
3Productivity
If rapid tissue processing is performed to prevent cell deterioration, then productivity increases, but manufacturing precision decreases due to rushed procedures
Solution Approach 1:
The disaggregation module performs preliminary mechanical and enzymatic breakdown of tissue before the enrichment and stabilization steps. By pre-processing the tissue to break it down into smaller fragments and release cells, the system enables subsequent rapid processing without compromising cell quality. This preliminary action ensures that even during fast processing, the TILs are properly liberated and maintained in a viable state.
Solution Approach 2:
Enzymes are used as intermediaries in the disaggregation process to facilitate tissue breakdown without mechanical stress that could damage cells. The enzymatic action gently releases TILs from the tissue matrix, maintaining cell integrity and viability while enabling rapid processing. This intermediary chemical approach ensures high processing speed without sacrificing manufacturing precision.
4Reliability
If oxygen is present during TIL processing, then normal cellular metabolism is maintained, but cell deterioration occurs due to oxidative stress
Solution Approach 1:
The stabilization module creates an oxygen-excluded environment that prevents oxidative damage to TILs during processing and storage. By removing oxygen, the system eliminates the harmful oxidative stress that would otherwise cause cell deterioration, while still maintaining cellular viability through anaerobic metabolic pathways. This inert environment preserves both the viability and the tumor microenvironment characteristics of the isolated TILs.
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 improves the viability and diversity of TIL populations, enabling more effective anti-tumor activity and clinical responses by maintaining the tumor environment's cellular diversity and reducing contamination and labor-intensive processes.
Implementation Method 1
a disaggregation module for receipt and processing of material comprising solid mammalian tissue
Implementation Method 2
processing the tumor into multiple tumor fragments
Implementation Method 3
cryopreserving the disaggregated tumor in the stabilization module
Implementation Method 4
an optional enrichment module for filtration of disaggregated solid tissue material and segregation of non-disaggregated tissue and filtrate
Data Source
AI summary
The present invention provides methods for isolating and cryopreserving tumor infiltrating lymphocytes (TILs) and producing therapeutic populations of TILs, including methods via use of a kit and a semi-automatic device for aseptic disaggregation, enrichment, and cryopreservation of a resected tumor prior to expansion of the TIL population. The present invention also provides methods for expansion, and/or stabilization of TILs, for instance UTILs, compositions involving the same and methods of treatment involving the same.