DMSO-Assisted Engineered Immune Cell Production for CAR-T Transduction
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Solution Overview
Problem
Existing methods for producing engineered immune cells, such as CAR-T cells, face challenges in transduction efficiency and the maintenance of high potency T cell populations, particularly naive and stem cell memory T cells, which are crucial for effective cell therapy.
Innovation Solution
The method involves culturing immune cells in the presence of dimethyl sulfoxide (DMSO) during activation, transduction, and optional ex vivo expansion steps to enhance transduction efficiency and increase the population of high potency T cells.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Reliability
If conventional transduction methods are used to produce engineered immune cells, then the process is simpler, but transduction efficiency is lower and high potency T cell populations are not maintained
Solution Approach 1:
The patent applies parameter changes by introducing DMSO at specific concentrations (0.001-3% v/v) during culture steps to enhance transduction efficiency and maintain high potency T cell populations. This chemical parameter modification directly addresses the transduction efficiency problem without fundamentally changing the overall culture process architecture.
Solution Approach 2:
The patent implements preliminary action by pre-treating T cells with DMSO before transduction and maintaining it during early culture steps. This preparatory exposure to DMSO primed the cells for more efficient transduction and better maintenance of naive and stem cell memory T cell populations before the actual transduction event.
2Reliability
If DMSO is added to enhance transduction efficiency, then transduction efficiency increases, but the concentration must be precisely controlled
Solution Approach 1:
The patent establishes specific DMSO concentration ranges (0.001-3% v/v) as optimal parameters for enhancing transduction efficiency. By defining this parameter window, the patent balances the benefit of improved transduction against the risk of concentration-related adverse effects, providing a practical manufacturing guideline.
Solution Approach 2:
The patent incorporates monitoring and control mechanisms to maintain DMSO concentrations within the specified range during culture. This feedback approach ensures that transduction efficiency is maximized while preventing DMSO concentration from reaching levels that could harm cell viability or function.
3Quantity of substance
If high potency T cell populations are maintained through extended culture, then more naive and stem cell memory T cells are preserved, but culture time increases
Solution Approach 1:
The patent uses DMSO pre-treatment and maintenance during early culture steps to prime and protect high potency T cell populations before they undergo transduction and expansion. This preliminary protection allows the cells to maintain their naive and stem cell memory characteristics throughout the culture process without requiring extended culture times.
Solution Approach 2:
The patent employs DMSO concentration optimization as a control parameter to maintain high potency T cell populations throughout the culture process. By adjusting and maintaining appropriate DMSO levels, the patent preserves the desired T cell subsets without needing to extend culture duration, thus avoiding the time loss associated with prolonged cultivation.
Data Source
AI summary
The present disclosure provides improved methods of producing engineered immune cells (e.g., CAR-T cells). The resulting engineered immune cells and compositions comprising the same are useful in treating various diseases, e.g., infection, autoimmune diseases, and tumors.