Memory-like NK Cell Production for Cancer Therapy

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Solution Overview

Problem

Current methods for producing NK cells for cancer therapy are limited by the short survival and activity duration of NK cells, requiring frequent injections and relying on large blood volumes, which is burdensome for patients and donors.

Innovation Solution

A method for producing memory-like NK cells involves isolating peripheral blood mononuclear cells, treating them with specific cytokines and antibodies, and culturing them under controlled conditions to enhance their proliferation and cancer-killing capabilities.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Reliability

If conventional NK cells are used for cancer therapy, then they can kill cancer cells, but they have short survival duration and require frequent injections

Engineering Contradiction:
Improvecancer cell killing abilityVSAvoidsurvival duration
Core Design Contradiction:
ReliabilityVSDuration of action of moving object

Solution Approach 1:

The patent applies preliminary action by pre-culturing and activating NK cells in the laboratory before administration to patients. The NK cells are expanded and primed in advance under controlled conditions with cytokines and target cell stimuli, so that when infused, they are already in an activated state capable of immediate cancer cell killing, thereby extending their functional duration in the patient's body.

Inventive Principle:
Principle #10Preliminary action

Solution Approach 2:

The patent changes the physiological parameters of NK cells through controlled culture conditions, cytokine treatment, and activation stimuli during the production process. By manipulating these parameters in the laboratory, the NK cells are transformed into a more stable, long-lasting population with enhanced survival and functional persistence in the patient.

Inventive Principle:
Principle #35Parameter changes

2Quantity of substance

If large blood volumes are used to secure sufficient NK cells, then adequate cell numbers can be obtained, but it becomes burdensome for donors

Engineering Contradiction:
ImproveNK cell numberVSAvoiddonor burden
Core Design Contradiction:
Quantity of substanceVSEase of operation

Solution Approach 1:

The patent applies local quality by selectively expanding and activating only the NK cell population from the donor's blood, rather than requiring large volumes of whole blood. Through targeted culture conditions and activation stimuli, the NK cells are selectively proliferated and activated in the laboratory, concentrating the functional cells from a small initial sample into a sufficient therapeutic dose.

Inventive Principle:
Principle #3Local quality

Solution Approach 2:

The patent changes the quantitative parameters of NK cell production by using cytokine-driven expansion and activation protocols that dramatically increase cell numbers from small initial samples. This parameter change allows sufficient therapeutic cell doses to be obtained from minimal donor blood volumes, reducing donor burden while maintaining adequate cell numbers for treatment.

Inventive Principle:
Principle #35Parameter changes

3Reliability

If NK cells are activated to enhance cancer-killing ability, then cytotoxicity increases, but their survival and persistence decrease

Engineering Contradiction:
ImprovecytotoxicityVSAvoidpersistence in body
Core Design Contradiction:
ReliabilityVSDuration of action of stationary object

Solution Approach 1:

The patent applies preliminary action by performing activation and expansion in the laboratory before administration. The NK cells are pre-activated and expanded under controlled conditions with appropriate cytokines and target cell stimuli, so that when infused, they maintain a balance between activation status and survival capability. This preliminary preparation ensures both high cytotoxicity and prolonged persistence in the patient's body.

Inventive Principle:
Principle #10Preliminary action

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 produced memory-like NK cells exhibit enhanced cancer cell killing ability, prolonged survival in vivo (up to 2 months), and the ability to be re-activated and proliferate upon secondary stimulus, making them suitable for repeated use in cancer therapy.

Implementation Method 1

treating them with specific cytokines and antibodies

Methodology Applied
Scientific EffectCytokine signaling:

Implementation Method 2

enhance their proliferation and cancer-killing capabilities

Methodology Applied
Scientific EffectCell proliferation:

Implementation Method 3

The Perforin gathers on the cell membrane of the target cell to form a complex and punctures the cell membrane to cause cell lysis

Methodology Applied
Scientific EffectPerforin-mediated cell lysis:

Implementation Method 4

the Granzyme is introduced into the cells through the holes generated in the cells to not only activate caspase, but also cause apoptosis through various mechanisms

Methodology Applied
Scientific EffectGranzyme-induced apoptosis:

Implementation Method 5

The NK cells induce apoptosis of cancer cells by binding to the death receptors of cancer cells using death ligands such as FasL and TRAIL

Methodology Applied
Scientific EffectDeath receptor binding:

Data Source

PatentUS20250109382A1Method for producing memory-like natural killer cells and anticancer use of memory-like natural killer cells produced thereby
Publication Date: 2025.04.03 ELPHIS CELL THERAPEUTICS
  • US20250109382A1 patent drawing
  • US20250109382A1 patent drawing
  • US20250109382A1 patent drawing

AI summary

The present invention relates to a method for producing memory-like natural killer (NK) cells and anticancer use of memory-like NK cells produced thereby. The method for producing memory-like NK cells, according to the present invention, is an optimal autoimmune cell culture method for producing memory-like NK cells with an increased ability to kill cancer cells while the proliferation thereof is maintained. Memory-like NK cells produced thereby have an excellent ability to kill cancer cells compared to NK cells, have a memory-like ability, thus having the ability to be activated again and proliferate again when a second stimulus is applied, and has the advantage of being able to survive for 2 months or longer in vivo, and thus can be used as an immune cell therapeutic agent or for the prevention or treatment of cancer.