BCMA, NKG2D, and CD16 Multi-Specific Proteins for Cancer Cell Killing

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Solution Overview

Problem

Current cancer treatments, including those for prostate and breast cancer, are not effective for all patients and can have significant adverse side effects, while existing cancer immunotherapies using bi-specific T-cell engagers and antibodies are limited in their ability to target and destroy cancer cells effectively.

Innovation Solution

Development of multi-specific binding proteins that bind to BCMA, NKG2D, and CD16 receptors to activate natural killer (NK) cells and cytotoxic T cells, enhancing their ability to kill cancer cells by engaging multiple activating receptors and blocking natural ligands.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Reliability

If multi-specific binding proteins are used to engage multiple activating receptors, then the potency and lysis of target cells is improved, but the device complexity increases

Engineering Contradiction:

Improvepotency and lysis of target cellsVSAvoidcomplexity of binding protein structure

Core Design Contradiction:

ReliabilityVSDevice complexity

Solution Approach 1:

The patent combines multiple antigen-binding sites (anti-BCMA, anti-NKG2D, anti-CD16) into a single multi-specific binding protein molecule, enabling simultaneous engagement of multiple receptors on NK cells and target cells. This merging of multiple functions into one molecule increases potency and target cell lysis while managing structural complexity through integrated design

Inventive Principle:

Principle #5Merging (Combining)

Solution Approach 2:

The multi-specific binding protein is designed to perform multiple functions: binding BCMA on target cells, engaging NKG2D and CD16 receptors on NK cells, and blocking natural ligands. This multi-functionality allows a single agent to activate NK cells through multiple pathways simultaneously, enhancing overall potency without requiring multiple separate therapeutic agents

Inventive Principle:

Principle #6Universality (Multi-functionality)

2Reliability

If multi-specific binding proteins engage multiple receptors, then the effectiveness of cancer cell destruction is improved, but the treatment side effects may worsen

Engineering Contradiction:

Improveeffectiveness of cancer cell destructionVSAvoidtreatment side effects

Core Design Contradiction:

ReliabilityVSObject-generated harmful factors

Solution Approach 1:

The binding protein is designed with specific binding characteristics that localize its activity to cancer cells expressing BCMA. By targeting BCMA as an anchor and requiring co-engagement of NKG2D and CD16 on NK cells, the therapy achieves localized action at the tumor site, improving cancer cell destruction effectiveness while minimizing off-target effects and reducing treatment side effects

Inventive Principle:

Principle #3Local quality

3Reliability

If blocking natural ligands to NKG2D is implemented, then the specificity of NK cell activation is improved, but the loss of natural immune function worsens

Engineering Contradiction:

Improvespecificity of NK cell activationVSAvoidnatural immune function

Core Design Contradiction:

ReliabilityVSLoss of substance

Solution Approach 1:

The multi-specific binding protein acts as an intermediary that replaces natural ligands to activate NKG2D receptors. By providing an artificial but controlled activating signal through the binding protein, NK cells are specifically activated against BCMA-expressing cancer cells without requiring natural ligands, thereby achieving specific activation while preserving overall immune function

Inventive Principle:

Principle #24Intermediary (Mediator)

Data Source

PatentUS12384851B2Multi-specific binding proteins that bind BCMA, NKG2D and CD16, and methods of use

Publication Date: 2025.08.12 DRAGONFLY THERAPEUTICS INC

AI summary

Multi-specific binding proteins that bind to and kill human cancer cells are described, as well as pharmaceutical compositions and therapeutic methods useful for the treatment of cancer. The cancer can be B-cell maturation antigen (BCMA)-expressing cancer. The multi-specific binding proteins provided herein exhibit high potency and maximum lysis of target cells compared to anti-BCMA monoclonal antibodies.