NK Cell and CD123-Binding Protein Therapy for Leukemia

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Solution Overview

Problem

Current treatments for acute myeloid leukemia (AML), B-cell acute lymphoblastic leukemia (B-ALL), and myelodysplastic syndromes (MDS) are limited by resistance to conventional chemotherapy and the risk of graft-versus-host disease (GvHD) associated with hematopoietic stem cell transplantation (HSCT).

Innovation Solution

A composition comprising Natural Killer (NK) cells and a binding protein with specific antigen binding domains for CD123 and NKp46, which can be sourced from autologous or allogeneic donors and expanded in vitro or in vivo, is administered to patients. This composition enhances the immune response against leukemia cells without causing GvHD.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Reliability

If hematopoietic stem cell transplantation (HSCT) is used to treat leukemia, then long term survival is improved, but graft versus host disease (GvHD) and graft failure occur

Engineering Contradiction:

Improvelong term survivalVSAvoidgraft versus host disease

Core Design Contradiction:

ReliabilityVSObject-affected harmful factors

Solution Approach 1:

The patent extracts and isolates the beneficial anti-leukemia activity from HSCT by using purified NK cells instead of whole stem cell transplants. The NK cells are selected and expanded to provide anti-leukemia effects while leaving behind the harmful components that cause GvHD, such as T cells that can attack host tissues.

Inventive Principle:

Principle #2Taking out (Extraction)

Solution Approach 2:

The patent uses a bispecific binding protein as an intermediary molecule that bridges NK cells and leukemia cells. The binding protein has one arm that recognizes CD123 on leukemia cells and another arm that engages NK cell receptors, thereby mediating the cytotoxic effect without requiring direct cell-to-cell contact that would trigger GvHD.

Inventive Principle:

Principle #24Intermediary (Mediator)

2Productivity

If conventional chemotherapy is used to treat leukemia, then initial disease control is achieved, but resistance develops leading to relapse

Engineering Contradiction:

Improveinitial disease controlVSAvoiddisease relapse

Core Design Contradiction:

ProductivityVSReliability

Solution Approach 1:

The patent replaces the chemical mechanism of conventional chemotherapy with a biological mechanism using NK cells. Instead of using chemotherapeutic agents that leukemia cells can develop resistance against, the treatment uses living immune cells that can recognize and kill leukemia cells through multiple mechanisms including direct cytotoxicity and cytokine release, making resistance less likely to develop.

Inventive Principle:

Principle #28Mechanics substitution (Replace mechanical system)

Solution Approach 2:

The patent employs the patient's own immune system (NK cells) to fight the leukemia. The NK cells are isolated, expanded, and reinfused to provide sustained anti-leukemia activity. This self-service approach allows the immune system to continuously adapt and respond to leukemia cells, preventing relapse that occurs with chemotherapy.

Inventive Principle:

Principle #25Self-service

3Object-affected harmful factors

If NK cells are used to treat leukemia, then GvHD is avoided, but treatment efficacy needs enhancement

Engineering Contradiction:

ImproveGvHD avoidanceVSAvoidtreatment efficacy

Core Design Contradiction:

Object-affected harmful factorsVSReliability

Solution Approach 1:

The patent changes key parameters of NK cells to enhance their efficacy. This includes expanding NK cells ex vivo to increase their numbers, activating them through cytokine stimulation, and engineering them with enhanced receptors or costimulatory molecules. These parameter changes boost the potency of NK cells while maintaining their safety profile of not causing GvHD.

Inventive Principle:

Principle #35Parameter changes

Solution Approach 2:

The patent creates a composite therapeutic product combining NK cells with a bispecific binding protein. The NK cells provide the cytotoxic effector function while the binding protein provides targeted recognition and enhancement of NK cell activation. This composite approach synergistically enhances treatment efficacy while maintaining the safety advantage of NK cell-based therapy.

Inventive Principle:

Principle #40Composite materials

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 use of NK cells and the binding protein effectively targets and eliminates leukemia cells, potentially leading to complete remission without the adverse effects of GvHD, thus providing a safer and more effective treatment option for patients with hematological malignancies.

Implementation Method 1

a binding protein comprising a first antigen binding domain with binding specificity to CD123 and a second antigen binding domain with binding specificity to NKp46

Methodology Applied

Scientific EffectAntigen-antibody binding:

Data Source

PatentUS20250064935A1Natural killer cells and CD123 NK cell engager combination therapy

Publication Date: 2025.02.27 SANOFI SA(FR)

AI summary

Provided herein are compositions and methods of treating or preventing a hematological disease or disorder in a subject in need thereof, comprising expanded NK cells and a binding protein comprising a first antigen binding domain with binding specificity to CD123 and a second antigen binding domain with binding specificity to NKp46.