NK Cell Suspension Composition for Post-Thaw Cytotoxic Activity
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Solution Overview
Problem
Existing methods for preserving and administering highly active NK cells face challenges such as difficulty in collecting sufficient cells, variability in activation and proliferation, and the need for immediate treatment, with existing solutions not adequately maintaining cytotoxic activity post-thawing.
Innovation Solution
A solution for suspending cells that contains potassium ions, specific organic acids (succinic, malic, lactic, or acetic acid), and excludes chloride, calcium, and glucose, with a pH of 4.9 or higher, to maintain cytotoxic activity and suitability for infusion.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Reliability
If cells are preserved in conventional solutions containing chloride ions, glucose, and calcium ions, then short-time preservation is achieved, but cytotoxic activity is not maintained after thawing
Solution Approach 1:
The patent changes the chemical parameters of the preservation solution by excluding chloride ions (at concentrations of 135 mEq/L or higher), glucose (at concentrations of 5.55 mM or higher), and calcium ions (at concentrations of 0.423 mM or higher), while incorporating specific organic acids (succinic, malic, lactic, or acetic acid) to maintain pH at 4.9 or higher. This parameter modification enables the solution to maintain cytotoxic activity of NK cells after thawing, resolving the contradiction between preservation effectiveness and post-thaw functionality.
2Quantity of substance
If cells are activated and proliferated in vitro before administration, then sufficient cell quantity is obtained, but treatment time is extended
Solution Approach 1:
The patent enables preliminary activation and proliferation of NK cells in vitro using the specialized preservation solution, which maintains cell viability and cytotoxic activity during the expansion period. The solution's composition (excluding chloride, glucose, and calcium ions while including organic acids) allows cells to be prepared in advance and stored while maintaining high activity levels, thus enabling sufficient cell quantity to be obtained without compromising treatment timing.
3Reliability
If cells are harvested from the patient himself/herself to avoid rejection, then immune compatibility is achieved, but sufficient cell collection is difficult
Solution Approach 1:
The patent enables preliminary collection and expansion of autologous NK cells using the specialized preservation solution that maintains cell viability and cytotoxic activity. By allowing cells to be harvested, activated, and proliferated in vitro with maintained integrity, the solution enables sufficient cell quantities to be obtained from the patient's own cells while preserving immune compatibility, thus resolving the contradiction between obtaining enough cells and maintaining immune compatibility.
Data Source
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AI summary
An object of the present invention is to provide a solution for thawing that can maintain or improve the cytotoxic activity of highly active NK cells and the like after thawing. A solution for suspending cells for administration to humans, which satisfies the following criteria: (1) containing potassium ion, (2) having a pH of 4.9 or higher, (3) not containing chloride ions at a concentration of 135 mEq/L or higher, (4) not containing glucose at a concentration of 5.55 mM or higher, (5) not containing calcium ions at a concentration of 0.423 mM or higher, (6) having an osmolarity of 200 to 396 mOsm, and (7) containing any organic acid(s) selected from the group consisting of succinic acid, malic acid, lactic acid, citric acid, and acetic acid.