CD70-Targeting CAR-NK Cells for Neoplastic Disease Treatment

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Solution Overview

Problem

Current treatments for neoplastic diseases, particularly those involving CD70-positive malignancies and tumor microenvironment cells like cancer-associated fibroblasts, are limited in effectively targeting and eliminating these immunosuppressive cells, which hinder the immune system's ability to clear tumors.

Innovation Solution

Engineering natural killer (NK) cells to express a chimeric antigen receptor (CAR) comprising the extracellular domain of CD27 or a CD70-binding portion, allowing them to specifically target and eliminate CD70-positive cancer cells and tumor microenvironment cells, thereby enhancing the immune system's ability to combat neoplastic diseases.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Reliability

If conventional treatments are used for neoplastic diseases, then general tumor treatment is provided, but the ability to effectively target and eliminate CD70-positive cells and immunosuppressive tumor microenvironment cells is limited

Engineering Contradiction:

Improveeffectiveness of targeting CD70-positive cellsVSAvoidability to target different cell types in tumor microenvironment

Core Design Contradiction:

ReliabilityVSAdaptability or versatility

Solution Approach 1:

The CAR-NK cell construct is designed to universally target CD70 antigen expressed on multiple cell types including cancer cells and cancer-associated fibroblasts (CAFs) in the tumor microenvironment, providing multi-functional anti-tumor activity through a single therapeutic agent

Inventive Principle:

Principle #6Universality (Multi-functionality)

Solution Approach 2:

The invention changes the target parameter from general tumor markers to the specific CD70 antigen, enabling reliable and selective identification and elimination of CD70-positive malignant cells and immunosuppressive microenvironment cells

Inventive Principle:

Principle #35Parameter changes

2Productivity

If CD70-positive tumor microenvironment cells are not targeted, then the immune system can clear tumors more effectively, but the immunosuppressive character of the tumor microenvironment hinders immune clearance

Engineering Contradiction:

Improverate of immune clearanceVSAvoidimmunosuppression by tumor microenvironment cells

Core Design Contradiction:

ProductivityVSObject-generated harmful factors

Solution Approach 1:

The invention converts the harmful immunosuppressive function of CD70-positive tumor microenvironment cells into a beneficial target for immune attack, where the same CD70 antigen that mediates immunosuppression becomes the ligand for CAR-NK cell recognition and elimination of these suppressive cells

Inventive Principle:

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

Solution Approach 2:

The CAR-NK cells act as an intermediary therapeutic agent that bridges the gap between the immune system and CD70-positive target cells, enabling the immune system to recognize and eliminate immunosuppressive cells that would otherwise protect the tumor

Inventive Principle:

Principle #24Intermediary (Mediator)

Data Source

PatentUS20240115606A1Cell-Based Therapeutics Targeting CD70

Publication Date: 2024.04.11 UNIVERSITEIT ANTWERPEN

AI summary

The invention provides a natural killer (NK) cell engineered to express a chimeric antigen receptor (CAR), wherein the CAR comprises the extracellular domain of CD27 or a CD70-binding portion thereof, as well as compositions comprising the engineered NK cell, methods for producing the engineered NK cell, and therapeutic applications of the engineered NK cell, such as for treating neoplastic diseases.