Cryopreservation Composition With ADAM17 Inhibitors for Cell Function
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Solution Overview
Problem
Standard cryopreservation methods can damage cells, particularly affecting the quality and functionality of Regulatory T cells (Treg) and Natural Killer (NK) cells, leading to loss of their regulatory or killing properties after thawing.
Innovation Solution
The use of cryopreservation compositions containing ADAM metallopeptidase domain 17 (ADAM17) inhibitors, along with cryoprotectants and serum, in an aqueous solution, to preserve cell surface markers and maintain cell functionality during freezing and thawing.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Duration of action of stationary object
If standard cryopreservation methods are used, then cells can be preserved for prolonged time, but cell quality and functionality are damaged
Solution Approach 1:
The patent modifies the chemical composition parameters of the cryopreservation medium by incorporating ADAM17 inhibitors (such as TAPI-2, GI-5402, or GI-245402) at specific concentrations (e.g., 10-100 μM). This parameter change prevents ADAM17-mediated shedding of cell surface markers like CD16 and CD62L during freezing and thawing, thereby maintaining cell functionality while enabling prolonged storage.
Solution Approach 2:
The ADAM17 inhibitor acts as an intermediary substance that blocks the harmful enzymatic activity of ADAM17. By introducing this mediator into the cryopreservation medium, the patent prevents the direct damage that would otherwise occur between freezing stress and cell surface markers, preserving marker integrity without altering the fundamental cryopreservation process.
2Ease of operation
If standard cooling profiles are used, then cryopreservation process is simplified, but cells of various tissue and donor source are not universally preserved
Solution Approach 1:
The patent creates a universal cryopreservation medium formulation that works across multiple cell types (T cells, NK cells, Treg cells) and donor sources. The inclusion of ADAM17 inhibitors provides a common protective mechanism that addresses the specific vulnerability of different cell types to ADAM17-mediated marker shedding, making the process universally applicable without requiring cell-type-specific optimization.
3Device complexity
If cryopreservation is performed without ADAM17 inhibitors, then process is simpler, but cell surface markers are lost
Solution Approach 1:
The ADAM17 inhibitor is incorporated into the cryopreservation medium before the freezing process begins. This preliminary action ensures that the inhibitor is already present and active when cells are exposed to freezing stress, preventing marker shedding from the outset rather than requiring post-thaw intervention or complex multi-step protocols.
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
The method preserves cell surface markers and viability, ensuring that NK and T cells retain their functional properties post-thawing, suitable for effective cell therapies.
Implementation Method 1
cryopreservation compositions having a cryopreservation medium having at least one ADAM metallopeptidase domain 17 (ADAM17) inhibitor
Implementation Method 2
cryopreservation compositions herein can further include one or more cryoprotectants
Data Source
AI summary
The disclosure provides for cryopreservation compositions and methods of use thereof. Aspects of the present disclosure provide for cryopreservation compositions useful in the freezing and thawing of cell therapies. Other aspects of the present disclosure provide for systems for use in the cryopreservation cell therapies. Still other aspects of the present disclosure provide for methods of cryopreserving cell therapies.