Pre-Activated NK Cell Expansion Using Cytokines and CD137 aAPCs

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Solution Overview

Problem

Existing methods for activating and expanding natural killer (NK) cells for therapeutic use are limited by the need for complex and costly procedures like leukapheresis to obtain sufficient numbers, and there is a lack of effective strategies for producing highly functional pre-activated NK cells.

Innovation Solution

A method involving pre-activation of NK cells with IL-12, IL-15, and IL-18 followed by expansion using artificial antigen presenting cells (aAPCs) expressing CD137 ligand, such as engineered K562 cells, to produce expanded NK cells.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Quantity of substance

If NK cells are directly isolated from peripheral blood without ex vivo expansion, then the procedure is simpler, but the number of NK cells obtained is insufficient for therapeutic use

Engineering Contradiction:

Improvenumber of NK cellsVSAvoidprocedure complexity

Core Design Contradiction:

Quantity of substanceVSDevice complexity

Solution Approach 1:

The patent applies preliminary action by performing ex vivo expansion of NK cells before therapeutic administration. NK cells are isolated from peripheral blood, pre-activated with cytokines (IL-12, IL-15, IL-18), and then expanded in culture using artificial antigen-presenting cells. This preliminary expansion step generates sufficient numbers of functional NK cells for therapy, resolving the contradiction between obtaining adequate cell quantities and avoiding complex procedures.

Inventive Principle:

Principle #10Preliminary action

2Reliability

If NK cells are pre-activated with IL-18, IL-15, and IL-12, then the functional competency and cytokine production are enhanced, but the number of cells remains insufficient without expansion

Engineering Contradiction:

Improvefunctional competencyVSAvoidnumber of NK cells

Core Design Contradiction:

ReliabilityVSQuantity of substance

Solution Approach 1:

The patent merges two critical functions into a single expansion culture system: (1) pre-activation with cytokines (IL-12, IL-15, IL-18) to enhance functional competency, and (2) expansion using artificial antigen-presenting cells to increase cell numbers. This combined approach simultaneously achieves both enhanced functionality and sufficient quantity, resolving the contradiction between these two requirements.

Inventive Principle:

Principle #5Merging (Combining)

3Quantity of substance

If leukapheresis is used to obtain sufficient NK cells, then adequate numbers can be obtained, but the procedure is complicated and costly

Engineering Contradiction:

Improvenumber of NK cellsVSAvoidprocedure simplicity

Core Design Contradiction:

Quantity of substanceVSEase of manufacture

Solution Approach 1:

The patent uses copying by creating artificial antigen-presenting cells (aAPCs) that replicate and present antigens to NK cells in culture. These aAPCs (derived from leukemia cells engineered to express CD137 ligand) serve as surrogate APCs that enable NK cell expansion without requiring complex leukapheresis procedures. This copying approach generates sufficient NK cells through in vitro culture, simplifying the overall process while maintaining adequate cell numbers for therapy.

Inventive Principle:

Principle #26Copying

Data Source

PatentUS12473336B2Methods for activation and expansion of natural killer cells and uses thereof

Publication Date: 2025.11.18 BOARD OF RGT THE UNIV OF TEXAS SYST

AI summary

Provided herein are methods for pre-activating and expanding an isolated population of NK cells. Further provided herein are methods for the treatment of cancer by administering the pre-activated and expanded NK cells.