Keap1-Deleted NK Cells Enhance Anticancer Activity

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Solution Overview

Problem

Natural Killer (NK) cells, crucial for cancer immunotherapy, are often in an inactivated state and require activation to effectively target tumor cells, and existing antioxidant mechanisms like Keap1-Nrf2 signaling can limit their anticancer function.

Innovation Solution

Deleting the Keap1 gene in NK cells or culturing them in an antioxidant-rich medium enhances their antioxidant activity and anticancer function, leading to increased cytotoxicity against cancer cells.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Reliability

If Keap1-Nrf2 signaling mechanism is activated to regulate ROS production, then antioxidant protection is improved, but anticancer function of NK cells is suppressed

Engineering Contradiction:

Improveantioxidant protectionVSAvoidanticancer function

Core Design Contradiction:

ReliabilityVSProductivity

Solution Approach 1:

The patent extracts and removes the Keap1 component from the Keap1-Nrf2 signaling pathway through genetic deletion. This extraction eliminates the inhibitory constraint that Keap1 imposes on Nrf2, thereby resolving the contradiction by allowing antioxidant mechanisms to function without suppressing anticancer activity. The removal of Keap1 enables Nrf2 to activate antioxidant genes while maintaining NK cell cytotoxicity.

Inventive Principle:

Principle #2Taking out (Extraction)

2Productivity

If NK cells are activated to enhance anticancer function, then cytotoxicity against tumor cells is improved, but ROS production increases causing oxidative stress

Engineering Contradiction:

ImprovecytotoxicityVSAvoidoxidative stress

Core Design Contradiction:

ProductivityVSObject-affected harmful factors

Solution Approach 1:

The patent converts the harmful effect of ROS production into a beneficial outcome by deleting Keap1. The increased ROS production during NK cell activation, which would normally cause oxidative stress and damage, is transformed into an advantageous state where enhanced ROS levels contribute to anticancer activity while the deleted Keap1 prevents excessive oxidative stress accumulation. This converts what was previously a harmful factor into a beneficial component of the anticancer mechanism.

Inventive Principle:

Principle #22Blessing in disguise (Convert harm into benefit)

3Object-affected harmful factors

If antioxidant activity is enhanced through Keap1 deletion, then protection against oxidative stress is improved, but ROS signaling for immune activation is reduced

Engineering Contradiction:

Improveoxidative stress protectionVSAvoidimmune activation

Core Design Contradiction:

Object-affected harmful factorsVSProductivity

Solution Approach 1:

The patent changes the parameter of antioxidant enzyme expression levels by deleting Keap1, which leads to constitutive activation of Nrf2 and upregulation of antioxidant genes. This parameter change creates a new state where antioxidant protection is enhanced while the Keap1 deletion specifically in NK cells preserves the ability of ROS to function as activation signals, resolving the contradiction through selective genetic modification.

Inventive Principle:

Principle #35Parameter changes

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

Keap1 gene-deleted NK cells or those cultured with antioxidants exhibit enhanced anticancer activity, making them effective for preventing and treating cancer diseases.

Implementation Method 1

The Keap1-Nrf2 signaling mechanism is a representative antioxidant mechanism in our body that is responsible for regulation of production of reactive oxygen species (ROS)

Methodology Applied

Scientific EffectKeap1-Nrf2 signaling mechanism:

Implementation Method 2

an antioxidant mechanism in our body that is responsible for regulation of production of reactive oxygen species (ROS)

Methodology Applied

Scientific EffectAntioxidant mechanism:

Data Source

PatentUS20240408140A1Enhancing anticancer function of natural killer cell through regulation of antioxidant mechanism

Publication Date: 2024.12.12 DAEGU GYEONGBUK INSTITUTE OF SCIENCE AND TECHNOLOGY

AI summary

The present invention relates to enhancing the anticancer function of a natural killer (NK) cell through the regulation of an antioxidant mechanism and confirms that, in comparison to a conventional NK cell, anticancer activity is enhanced in an NK cell having increased antioxidant activity due to the removal of the keap 1 gene or due to having been cultured in a medium containing an antioxidant material, and can thus be useful as a composition for preventing, treating, or alleviating cancer.