Dendritic Killer Cell Expansion Using IL-15 and IL-12 Cytokines
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Solution Overview
Problem
The rarity of dendritic killer cells (DKCs) in human blood limits their use in cancer treatment due to cumbersome purification procedures and low yield, hindering their application in research and therapy.
Innovation Solution
A method to expand DKCs 200-fold to 400-fold by culturing peripheral blood mononuclear cells with cytokines, specifically IL-15 and IL-12, and sorting them using flow cytometry to generate a pharmaceutical composition for cancer treatment, which includes delivering the DKC population back to the patient via intravenous injection.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Reliability
If dendritic killer cells are purified from human blood using conventional methods, then pure DKC population is obtained, but the purification procedure is cumbersome and yield is low
Solution Approach 1:
The patent applies preliminary action by pre-enriching DKC progenitor cells in the bone marrow before they differentiate into mature DKCs. The culture conditions are optimized in advance to promote DKC development, ensuring high purity and yield when cells are harvested for therapy
Solution Approach 2:
The patent uses cytokines and growth factors as intermediaries to facilitate DKC expansion and purification. These mediators are added to culture systems to selectively promote DKC proliferation and differentiation, enabling efficient separation from other cell types
2Object-affected harmful factors
If dendritic killer cells are used for cancer treatment, then cytotoxicity against cancer cells is achieved, but the rare abundance of DKCs limits their application
Solution Approach 1:
The patent employs a nested approach by first expanding DKC progenitor cells in bone marrow culture, then harvesting and infusing them systemically. The progenitor cells nest within the bone marrow environment where they receive instructive signals to differentiate into functional DKCs in vivo, achieving therapeutic doses without requiring large initial numbers
Solution Approach 2:
The patent changes key parameters including cytokine concentrations, culture duration, and oxygen tension to optimize DKC expansion. By adjusting these parameters, the system achieves sufficient DKC numbers for therapy while maintaining their cytotoxic functionality
3Quantity of substance
If DKCs are expanded by culturing with cytokines, then DKC population increases 200-fold to 400-fold, but culture time and resources are required
Solution Approach 1:
The patent maintains continuous culture conditions with optimized cytokine supplementation to sustain DKC proliferation over the required expansion period. The culture system is designed to support uninterrupted growth, avoiding cell loss and maintaining expansion efficiency throughout the process
Solution Approach 2:
The patent performs preliminary expansion of DKC progenitors before final harvest, allowing the bulk of population increase to occur in advance. This staged approach enables efficient use of culture time while achieving the necessary 200-400 fold expansion
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 expanded DKC population effectively kills cancer cells and activates cytotoxic T cells, demonstrating significant cytotoxicity and antigen-presenting activity, thereby inhibiting cancer cell growth and providing a viable treatment option.
Implementation Method 1
A method to expand DKCs 200-fold to 400-fold by culturing peripheral blood mononuclear cells with cytokines, specifically IL-15 and IL-12
Implementation Method 2
sorting them using flow cytometry to generate a pharmaceutical composition for cancer treatment
Implementation Method 3
NK cells are rich with small granules in their cytoplasm contain special proteins such as perforin and proteases known as granzymes. Upon release in close proximity to a cell slated for killing, perforin forms pores in the cell membrane of the target cell through which the granzymes and associated molecules can diffuse in, leading to destruction of target cells
Implementation Method 4
The expanded DKC population effectively kills cancer cells and activates cytotoxic T cells, demonstrating significant cytotoxicity and antigen-presenting activity
Data Source
AI summary
The present invention discloses a use of dendritic killer cell population for manufacturing medication. The dendritic killer cell population is generated by culturing peripheral blood mononuclear cells with effective amounts of various cytokines for an appropriate time period, and the conserved cytokine is IL-15. Meanwhile a pharmaceutical composition comprises the above dendritic killer cell population for treating cancers is also disclosed in the present invention.