Pyruvate Potentiation of NK Cells for Enhanced Cytotoxicity
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Solution Overview
Problem
There is a need for an effective method to enhance the activities of Natural Killer (NK) cells, which are crucial for immunotherapies but require potentiation to improve their effector functions.
Innovation Solution
The use of pyruvate at supra-physiological concentrations (0.35 to 10 mM) to potentiate NK cells in vitro, enhancing their effector functions such as cytokine production and cytotoxicity.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Reliability
If NK cells are cultured in conventional media with physiological pyruvate concentrations, then cell survival is maintained, but effector functions remain insufficient for effective immunotherapy
Solution Approach 1:
The invention changes the concentration parameter of pyruvate from physiological levels (typically 0.1-0.5 mM in standard media) to supra-physiological levels (1-10 mM), fundamentally altering the metabolic state of NK cells to achieve enhanced effector functions including increased cytotoxicity and cytokine production
Solution Approach 2:
The invention applies preliminary metabolic conditioning by pre-incubating NK cells with high pyruvate concentrations (1-10 mM) for 16-24 hours before therapy, which potentiates the cells' effector functions in advance, making them more effective when administered to patients
2Reliability
If pyruvate concentration is increased to supra-physiological levels (1-10 mM), then NK cell effector functions are potentiated, but deviation from physiological conditions may affect cell viability
Solution Approach 1:
The invention uses complementary cytokines (IL-2, IL-15, IL-21) as protective agents during high pyruvate conditioning, which cushion the potential harmful effects of supra-physiological pyruvate concentrations while allowing the beneficial metabolic potentiation to occur, thereby maintaining both cell viability and enhanced effector functions
Solution Approach 2:
The invention maintains continuous exposure to optimized pyruvate concentrations (1-10 mM) combined with cytokine support throughout the conditioning period (16-24 hours), ensuring sustained metabolic potentiation without interruption that could compromise either cell viability or effector function development
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
Pyruvate supplementation significantly increases the intracellular ATP concentration and enhances the expression of activation markers in NK cells, leading to improved cytotoxicity and cytokine secretion.
Implementation Method 1
Pyruvate is a key metabolic intermediate that is taken up by cells and metabolized to generate ATP and other energy-rich molecules
Implementation Method 2
Pyruvate has been shown to activate several signaling pathways that are involved in NK cell activation and effector function
Data Source
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Figure 3a~3c
AI summary
The present invention relates to the use of pyruvate for potentiating natural killer (NK) cells in vitro. The present invention also relates to a method for treating in vitro NK cells, comprising the steps of providing NK cells from a subject; incubating the NK cells in the presence of pyruvate at a concentration of from 0.35 to 10 mM, thereby potentiating the NK cells; and collecting the potentiated NK cells.