TIL Expansion Using Allogeneic Feeder Cells
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Solution Overview
Problem
Current methods for expanding tumor infiltrating lymphocytes (TILs) for cancer treatment are limited by length, cost, and sterility concerns, requiring large amounts of irradiated allogeneic cells and high doses of IL-2, which are logistically and regulatorily challenging, and do not efficiently prime TILs for expansion.
Innovation Solution
A novel TIL expansion process that includes antigen-presenting feeder cells from the initiation of expansion to prime TILs, reducing overall expansion time by using a two-step process with priming and rapid expansion phases, utilizing IL-2 and OKT-3, and optimizing APCs and culture supernatants to enhance TIL growth.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Productivity
If traditional REP method is used to expand TILs, then high fold expansion (1000-fold) is achieved, but the process requires large amounts of irradiated allogeneic PBMCs and high doses of IL-2, increasing cost and logistical complexity
Solution Approach 1:
The patent extracts and eliminates the requirement for large amounts of irradiated allogeneic PBMCs from the expansion process. By using a reduced number of irradiated allogeneic TILs instead of PBMCs as feeder cells, the method simplifies the process while maintaining high expansion efficiency.
Solution Approach 2:
The patent changes the parameters of the expansion process by reducing the number of feeder cells required and optimizing IL-2 dosing. This allows achieving high fold expansion with lower amounts of biological materials and reduced process complexity.
2Productivity
If traditional REP method is used to expand TILs, then sufficient TIL numbers are obtained, but the process takes 14 days, which is time-consuming for clinical application
Solution Approach 1:
The patent applies preliminary action by pre-expanding the allogeneic feeder TILs before use in the REP process. This pre-preparation of feeder cells optimizes their functionality and allows the main expansion process to proceed more efficiently, potentially reducing overall time while maintaining yield.
3Productivity
If traditional REP method is used, then TIL expansion is achieved, but sterility concerns and regulatory issues arise due to use of multiple donor PBMCs
Solution Approach 1:
The patent removes the source of sterility and regulatory concerns by eliminating the use of fresh allogeneic PBMCs from multiple donors. Instead, it uses irradiated allogeneic TILs from a single donor, which have already been processed and can be stored, thereby reducing sterility risks and simplifying regulatory compliance.
4Productivity
If large amounts of irradiated allogeneic PBMCs are used as feeder cells, then TIL expansion is supported, but cost and logistical burden increase significantly
Solution Approach 1:
The patent extracts the essential function of feeder cell support while eliminating the need for large quantities. By using irradiated allogeneic TILs instead of PBMCs, the method maintains TIL expansion capability with dramatically reduced amounts of feeder cells, lowering cost and logistical burden.
Solution Approach 2:
The patent employs irradiated allogeneic TILs that can be prepared in advance, stored, and used as disposable feeder cells. This approach replaces the need for fresh, living PBMCs from multiple donors with a more economical and logistically simpler alternative that maintains expansion support functionality.
Data Source
AI summary
The present invention provides improved and/or shortened methods for expanding TILs and producing therapeutic populations of TILs, including novel 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. Such TILs find use in therapeutic treatment regimens.