Tumor-Infiltrating Lymphocyte Expansion for High-Yield Cell Production
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Solution Overview
Problem
Conventional methods for producing tumor-infiltrating lymphocytes (TILs) face challenges with low yield and inefficiency in the culture and expansion processes, necessitating a more efficient process for TIL production.
Innovation Solution
A method involving culturing a tumor sample in a specific composition with controlled IL-2 concentration, followed by seeding and expanding immune cell populations in a gas-permeable container with optimized additive additions, achieving a high yield of TILs.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Reliability
If immune cells are cultured ex vivo to enhance anti-tumor activity, then the anti-tumor efficacy is improved, but the culture time required increases production cost and time
Solution Approach 1:
The patent changes the chemical parameters of the culture system by introducing specific small molecule compounds (e.g., PD-1 antagonist, IDO inhibitor, 2DG) that modify the immune cell activation pathway. This allows achieving enhanced anti-tumor activity without extending culture time, as the compounds directly stimulate immune cells rather than requiring prolonged in vivo expansion.
Solution Approach 2:
The patent uses small molecule compounds as intermediaries to transfer the anti-tumor effect. These compounds (PD-1 antagonist, IDO inhibitor, 2DG) act as mediators between the administered substances and the immune cells, enabling rapid activation and enhancement of immune cell function without requiring extended culture periods.
2Reliability
If multiple immune cell types are used to enhance anti-tumor activity, then the anti-tumor efficacy is improved, but the complexity of cell separation and culture increases
Solution Approach 1:
The patent segments the immune cell population into distinct types (NK cells, CD8+ T cells, CD4+ T cells, dendritic cells) and treats each segment with specific culture conditions and small molecule compounds optimized for that cell type. This segmentation allows for targeted enhancement of each cell type's anti-tumor function while simplifying the overall process compared to attempting to enhance all cell types simultaneously with a single approach.
Solution Approach 2:
The patent applies different small molecule compounds and culture conditions to different immune cell types based on their specific biological characteristics. For example, PD-1 antagonist is applied to T cells, while IDO inhibitor and 2DG are applied to dendritic cells and NK cells. This local quality approach optimizes the anti-tumor efficacy of each cell type without requiring complex unified separation systems.
3Reliability
If immune cells are activated in vivo before administration, then the anti-tumor activity is enhanced, but the risk of off-target effects and safety issues increases
Solution Approach 1:
The patent performs preliminary activation and enhancement of immune cells ex vivo before administration to the patient. The immune cells are cultured with small molecule compounds (PD-1 antagonist, IDO inhibitor, 2DG) and cytokines in controlled conditions to pre-activate them against tumor antigens. This preliminary action ensures the cells are ready for immediate anti-tumor action upon injection, avoiding the need for in vivo activation that could cause off-target effects.
Solution Approach 2:
The patent uses small molecule compounds as intermediaries to activate immune cells ex vivo in a controlled manner before administration. These compounds (PD-1 antagonist, IDO inhibitor, 2DG) mediate the activation process outside the patient's body, allowing precise control over which cells are activated and against what targets, thereby minimizing the risk of off-target effects compared to in vivo activation approaches.
Data Source
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AI summary
The present application relates to a method for producing an immune cell composition comprising tumor-infiltrating lymphocytes, and to uses of the immune cell composition produced thereby.