CD46 Modulators Targeting Tumor-Initiating Cells

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Solution Overview

Problem

Current cancer treatments are ineffective in targeting and eliminating cancer stem cells, leading to persistent tumors, recurrence, and metastasis, as these cells are resistant to traditional therapies and have deregulated pathways that promote continuous growth and self-renewal.

Innovation Solution

Development of CD46 modulators, including anti-CD46 antibodies and fusion constructs, that specifically target and reduce the frequency of tumor-initiating cells by binding to the CD46 protein, thereby inhibiting tumorigenesis, tumor maintenance, and metastasis.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Quantity of substance

If conventional cancer treatments (chemotherapy, radiotherapy, surgery) are used, then tumor mass can be reduced, but cancer stem cells persist and cause tumor recurrence and metastasis

Engineering Contradiction:
Improvetumor mass reductionVSAvoidtumor recurrence prevention
Core Design Contradiction:
Quantity of substanceVSReliability

Solution Approach 1:

The invention segments the tumor population by specifically targeting cancer stem cells (CSCs) as a distinct subpopulation from bulk tumor cells. The anti-CD46 antibody selectively binds to CSCs expressing CD46 marker, enabling differentiated treatment strategies that address the hierarchical structure of tumors and prevent recurrence by eliminating the regenerative CSC compartment while bulk tumor mass is reduced by conventional therapies

Inventive Principle:
Principle #1Segmentation

Solution Approach 2:

The anti-CD46 antibody serves as an intermediary agent that specifically recognizes and binds to CD46-expressing cancer stem cells. This antibody-mediated targeting enables selective delivery of therapeutic effects to CSCs, bridging the gap between conventional bulk tumor reduction and the need for specific CSC elimination to prevent recurrence

Inventive Principle:
Principle #24Intermediary (Mediator)

2Productivity

If traditional chemotherapeutic agents are used, then rapidly dividing tumor cells are killed, but cancer stem cells with slow proliferation are resistant and survive

Engineering Contradiction:
Improvetumor cell killing efficiencyVSAvoidcancer stem cell elimination
Core Design Contradiction:
ProductivityVSReliability

Solution Approach 1:

The invention employs dynamic treatment strategies that adapt to the different proliferation states of tumor cells. By using anti-CD46 antibody therapy that specifically targets CSCs regardless of their proliferation rate, the treatment dynamically addresses both rapidly dividing bulk cells (with conventional chemotherapy) and slow-proliferating CSCs (with antibody-mediated targeting), overcoming the kinetic resistance of CSCs to traditional chemotherapies

Inventive Principle:
Principle #15Dynamics

3Reliability

If targeted therapeutics are developed to address cancer stem cells, then tumor recurrence can be prevented, but treatment complexity and cost increase

Engineering Contradiction:
Improvetumor recurrence preventionVSAvoidtreatment regimen complexity
Core Design Contradiction:
ReliabilityVSDevice complexity

Solution Approach 1:

The anti-CD46 antibody provides universal targeting capability across multiple cancer types that express CD46 on their stem cells. This single antibody construct can be used in combination with various conventional therapies, offering a multi-functional approach that prevents recurrence without requiring entirely new complex treatment regimens for each cancer type

Inventive Principle:
Principle #6Universality (Multi-functionality)

Solution Approach 2:

The invention utilizes antibody copying of the natural immune recognition mechanism, where the anti-CD46 antibody mimics and enhances the body's natural ability to recognize and eliminate abnormal cells. This approach leverages existing biological pathways rather than creating entirely new complex mechanisms, reducing treatment complexity while maintaining effectiveness

Inventive Principle:
Principle #26Copying

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 CD46 modulators effectively decrease the frequency of tumor-initiating cells, inhibiting their ability to propagate and maintain tumors, leading to improved treatment outcomes by enhancing the effectiveness of cancer therapies and reducing recurrence and metastasis.

Implementation Method 1

anti-CD46 antibodies and fusion constructs, that specifically target and reduce the frequency of tumor-initiating cells by binding to the CD46 protein

Methodology Applied
Scientific EffectAntigen-antibody binding:

Data Source

PatentEP2611464B1Novel modulators and methods of use
Publication Date: 2018.04.25 ABBVIE STEMCENTRX LLC
  • EP2611464B1 patent drawingFigure 1A
  • EP2611464B1 patent drawingFigure 1B
  • EP2611464B1 patent drawingFigure 2

AI summary

Novel modulators, including antibodies and derivatives thereof, and methods of using such modulators to treat hyperproliferative disorders are provided.