NK Cell Expansion via Healthy Donor Conditioned Medium

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Solution Overview

Problem

Current methods for culturing NK cells are inefficient in increasing their numbers for therapeutic purposes, as they typically only multiply by 3 to 10 times the initial amount, and require multiple cytokines and selective classification, making them impractical for clinical application.

Innovation Solution

Culturing peripheral blood mononuclear cells (PBMCs) from cancer patients or healthy individuals in a medium containing a normal-person immune-cell cultured solution and a CD3 antibody, which increases NK cell content and cytotoxicity.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Productivity

If conventional methods using IL-2 or other cytokines are used to culture NK cells, then the number of NK cells increases to about 3 to 10 times the initial number, but this is insufficient for therapeutic purposes requiring mass production

Engineering Contradiction:

ImproveNK cell proliferation capacityVSAvoidfinal NK cell number

Core Design Contradiction:

ProductivityVSQuantity of substance

Solution Approach 1:

The patent applies preliminary action by pre-culturing healthy person's immune cells to generate a conditioned culture medium containing proliferation-promoting factors before using it to culture patient's NK cells. This pre-prepared medium is then used to stimulate rapid NK cell proliferation, achieving expansion beyond the conventional 3-10 fold increase without requiring multiple sequential culture steps

Inventive Principle:

Principle #10Preliminary action

Solution Approach 2:

The patent uses a culture medium conditioned by healthy person's immune cells as an intermediary substance that transfers proliferative signals from healthy immune cells to patient NK cells. This intermediary medium contains cytokines and growth factors that mediate the proliferation effect, eliminating the need for direct cell-to-cell contact or complex co-culture systems

Inventive Principle:

Principle #24Intermediary (Mediator)

2Reliability

If multiple interleukins and selective classification of NK cells in the PBMC stage are used, then NK cell culture can be achieved, but the process becomes complex and impractical for clinical application

Engineering Contradiction:

ImproveNK cell culture effectivenessVSAvoidculture process complexity

Core Design Contradiction:

ReliabilityVSDevice complexity

Solution Approach 1:

The patent extracts and utilizes only the essential proliferative factors present in healthy person's immune cell culture medium, eliminating the need for adding multiple individual interleukins (IL-2, IL-15, IL-21, etc.) separately. This extraction approach simplifies the culture system by using a single pre-conditioned medium rather than multiple cytokine additions

Inventive Principle:

Principle #2Taking out (Extraction)

Solution Approach 2:

The culture medium conditioned by healthy person's immune cells serves multiple functions simultaneously: it provides proliferation signals, maintains cell viability, and supports NK cell activation. This universal medium replaces the need for multiple separate culture components and selective classification procedures, making the process clinically feasible

Inventive Principle:

Principle #6Universality (Multi-functionality)

Data Source

PatentUS20220348873A1Method for increasing content of NK cells using culture medium of immune cells of healthy person

Publication Date: 2022.11.03 RA CORPORATION PTY LTD

AI summary

The present invention relates to a culture method for increasing the content of NK cells. According to the present invention, the growth rate of immune cells including NK cells can be increased not only in cancer patients but also in persons who are genetically susceptible to cancer or elderly people, and an NK cell fraction and cell-killing ability can also be enhanced.