T Cell Manufacturing via Shortened Resting Period
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Solution Overview
Problem
Current methods for manufacturing T cells for adoptive immunotherapy face challenges such as the need for individualized production, which is economically infeasible, and difficulties in obtaining sufficient autologous cells, especially in heavily pretreated patients.
Innovation Solution
A method involving the thawing of frozen peripheral blood mononuclear cells (PBMC), followed by a 4-hour resting period, activation with anti-CD3 and anti-CD28 antibodies, transduction with a viral vector, and expansion of the T cells to obtain a sufficient number of genetically modified T cells.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Reliability
If traditional overnight resting methods are used for T cell production, then cell viability is maintained, but manufacturing time is extended and productivity is reduced
Solution Approach 1:
The patent changes the resting time parameter from traditional overnight (12-24 hours) to a shortened 4-hour period. This parameter modification maintains cell viability while significantly reducing manufacturing time, thereby resolving the contradiction between reliability and productivity.
2Reliability
If individualized T cell production is implemented, then patient-specific efficacy is improved, but economic feasibility deteriorates
Solution Approach 1:
By optimizing the resting time parameter to 4 hours, the patent enables faster production cycles that can accommodate individualized patient-specific T cell production without proportionally increasing costs. This parameter change improves economic feasibility while maintaining patient-specific efficacy.
3Reliability
If autologous T cells are obtained from heavily pretreated patients, then treatment relevance is improved, but cell availability deteriorates
Solution Approach 1:
The patent incorporates a 4-hour resting period as a preliminary action step that prepares and optimizes the autologous T cells from heavily pretreated patients before activation and expansion. This preliminary resting phase enhances the quality and availability of cells, making them more suitable for therapy despite the patients' prior treatments.
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 method allows for the efficient production of T cells with enhanced expansion and viability, achieving at least 1.5 times greater fold expansion compared to traditional overnight resting methods, while reducing the overall manufacturing time.
Implementation Method 1
activation with anti-CD3 and anti-CD28 antibodies
Implementation Method 2
transduction with a viral vector
Data Source
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AI summary
The disclosure relates to methods of manufacturing T cells for adoptive immunotherapy. The disclosure further provides for methods of genetically transducing T cells, methods of using T cells, and T cell populations thereof. In an aspect, the disclosure provides for methods of thawing frozen peripheral blood mononuclear cells (PBMC), resting the thawed PBMC, activating the T cell in the cultured PBMC with an anti-CD3 antibody and an anti-CD28 antibody immobilized on a solid phase, transducing the activated T cell with a viral vector, expanding the transduced T cell, and obtaining expanded T cells.