Engineered NK Cell Activation With Antibody Binding for Cancer Targeting

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Solution Overview

Problem

Existing methods for using natural killer (NK) cells as a therapy face challenges such as limited numbers, insufficient persistence, cumbersome ex vivo expansion procedures, and poor cancer recognition and activation, hindering their efficacy in cancer treatment.

Innovation Solution

Compositions comprising engineered NK cells with transgenes and antibodies like Amivantamab, Margetuximab, and Imgatuzumab are developed, where the antibodies bind to the NK cells, enhancing their cancer antigen targeting capabilities and persistence.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Quantity of substance

If ex vivo expansion procedures are used to increase NK cell numbers, then the quantity of NK cells is improved, but the procedure complexity and time required are worsened

Engineering Contradiction:

ImproveNK cell numbersVSAvoidprocedure complexity

Core Design Contradiction:

Quantity of substanceVSDevice complexity

Solution Approach 1:

The patent applies preliminary action by pre-activating NK cells with cytokines (IL-15, IL-18, IL-12) before adoption into the patient, which enhances their functional competency and persistence without requiring complex ex vivo expansion procedures. This pre-activation prepares the cells to respond more effectively to tumor targets while avoiding the cumbersome expansion process.

Inventive Principle:

Principle #10Preliminary action

2Reliability

If pre-activation with cytokines is performed to enhance NK cell functionality, then the functional competency is improved, but the time required for activation is worsened

Engineering Contradiction:

Improvefunctional competencyVSAvoidactivation time

Core Design Contradiction:

ReliabilityVSLoss of time

Solution Approach 1:

The patent implements continuous useful action by using cytokine pre-activation that generates long-lived, memory-like NK cells with enhanced cytokine production upon re-stimulation. This continuous enhancement maintains functional competency over time rather than providing a transient effect, reducing the need for repeated activation cycles.

Inventive Principle:

Principle #20Continuity of useful action

3Ease of operation

If standard NK cell therapy is used, then the treatment is simpler to administer, but the persistence and efficacy against cancer is worsened

Engineering Contradiction:

Improveadministration simplicityVSAvoidNK cell persistence

Core Design Contradiction:

Ease of operationVSDuration of action of stationary object

Solution Approach 1:

The patent applies parameter changes by modifying NK cell properties through genetic engineering (introducing chimeric cytokine receptors and other transgenes) and cytokine pre-activation, which transforms standard NK cells into enhanced cells with improved persistence and cancer-killing capability while maintaining relative ease of administration through adoptive cell therapy.

Inventive Principle:

Principle #35Parameter changes

4Manufacturing precision

If NK cells are engineered with transgenes for enhanced cancer targeting, then the cancer recognition capability is improved, but the manufacturing complexity is worsened

Engineering Contradiction:

Improvecancer targeting accuracyVSAvoidengineering complexity

Core Design Contradiction:

Manufacturing precisionVSDevice complexity

Solution Approach 1:

The patent uses intermediary molecules such as chimeric cytokine receptors that mediate between the NK cell and cancer target, providing precise cancer recognition and targeting. These intermediary receptors act as bridges that enhance targeting accuracy without requiring complex multi-component engineering systems.

Inventive Principle:

Principle #24Intermediary (Mediator)

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 engineered NK cells with bound antibodies demonstrate enhanced cytotoxicity and tumor control in preclinical models, showing improved efficacy in treating various cancers.

Implementation Method 1

a complex between the engineered NK cell and Margetuximab, Amivantamab, and/or Imgatuzumab, through binding of the Fc region of the antibody to the engineered NK cell

Methodology Applied

Scientific EffectAntibody binding: Adsorption

Implementation Method 2

Cytokine stimulation constitutes an important signal to enhance the functional competency of NK cells to respond to tumor target cells

Methodology Applied

Scientific EffectCytokine stimulation:

Implementation Method 3

The engineered NK cells with bound antibodies demonstrate enhanced cytotoxicity and tumor control in preclinical models

Methodology Applied

Scientific EffectCytotoxicity:

Data Source

PatentUS20250228942A1Methods for activation and expansion of engineered natural killer cells and combinations with antibodies

Publication Date: 2025.07.17 BOARD OF RGT THE UNIV OF TEXAS SYST

AI summary

Embodiments of the disclosure concern methods and compositions related to preparation and use of combinatorial immunotherapies. In specific embodiments, compositions comprising engineered NK cells prepared in a particular manner also include certain antibodies. These compositions are utilized for treatment, such as for cancer treatment. In particular embodiments, the compositions include complexes of the engineered NK cells and the antibodies in which the antibody is bound to the engineered NK cells and may also bind to another antigen, such as on a cancer cell.