High-Purity NK Cell Production Using IL-15 and IL-21 Culture
Find Innovative SolutionsGenerate Solutions
Solution Overview
Problem
Existing methods struggle to produce a sufficient number of activated NK cells efficiently and economically for effective cancer therapy, particularly for solid tumors, and the therapeutic potential of NK cells is not fully realized due to difficulties in large-scale proliferation and differentiation.
Innovation Solution
A method involving the isolation of CD3-negative cells from monocytes, followed by treatment with IL-15 and IL-21, and subsequent culture to produce fresh, cold-preserved, or cryopreserved NK cells, which are then administered to treat various cancers.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Quantity of substance
If conventional methods are used to produce NK cells, then the production process is simple, but the number of activated NK cells produced is insufficient for effective cancer therapy
Solution Approach 1:
The production process is divided into distinct stages: isolation of CD3-negative cells from monocytes, treatment with specific cytokines (IL-15 and IL-21), and culture conditions optimized for NK cell differentiation. This segmentation allows each step to be optimized independently to maximize NK cell yield while maintaining process manageability
Solution Approach 2:
The method performs preliminary isolation and purification of CD3-negative cells before activation, ensuring that only the appropriate cell population is subjected to the complex activation protocol. This preliminary action prevents waste of resources on inappropriate cell types and streamlines the overall process
2Productivity
If conventional NK cell production methods are used, then the process is economical, but the time required to produce sufficient activated NK cells is excessive
Solution Approach 1:
The invention optimizes multiple parameters simultaneously: cytokine concentrations (IL-15 and IL-21), culture conditions, and cell density. These parameter changes create optimal conditions for rapid NK cell differentiation and activation, reducing production time while maintaining efficiency and economic feasibility
3Adaptability or versatility
If NK cells are cryopreserved for later use, then logistical flexibility is improved, but cell efficacy may be reduced
Solution Approach 1:
The method employs controlled phase transition through cryopreservation, transitioning cells from liquid to frozen state for storage and transport. The standardized cryopreservation protocol ensures that cells can be frozen, stored, and thawed while maintaining their therapeutic efficacy, thus enabling logistical flexibility without sacrificing reliability
Data Source
AI summary
Disclosed is a method for producing a large amount of natural killer cells and the use of the natural killer cells as an anticancer agent. The method produces fresh NK cells with high purity within a short time, and can also produce cold-preserved NK cells and thawed cryopreserved NK cells having efficacy comparable to the fresh NK cells. NK cells having efficacy comparable to the fresh NK cells can also be produced from cryopreserved CD3-negative cells. The fresh NK cells, cold-preserved NK cells and cryopreserved NK cells exhibit therapeutic effects against various cancers, including colorectal cancer, lung cancer, liver cancer, pancreatic cancer and leukemia, indicating these NK cells are effective as cellular therapeutic agents. Also disclosed are doses and methods of administration that show excellent effects when the fresh NK cells, cold-preserved NK cells and cryopreserved NK cells are used as pharmaceutical compositions for cellular therapy.