CCL20-Targeted Detection and Inhibition of Cancer Stem Cells

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Solution Overview

Problem

Current methods lack a consensus on surface marker phenotypes for human colorectal cancer stem cells (CSCs) and are inadequate in targeting CSCs, which are responsible for chemoresistance, metastasis, and relapse in cancer therapies.

Innovation Solution

The method involves using an agent that binds to CCL20 nucleic or amino acid sequences to detect and quantify CSCs, leveraging the overexpression of CCL20 by CSCs, which drives self-renewal and proliferation through its receptor CCR6, and using neutralizing antibodies to inhibit CSC activity.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Reliability

If conventional cancer therapy methods are used, then initial therapeutic response is achieved, but cancer stem cells survive and cause relapse and metastasis

Engineering Contradiction:
Improvetherapeutic responseVSAvoidchemoresistance and relapse
Core Design Contradiction:
ReliabilityVSObject-generated harmful factors

Solution Approach 1:

The patent extracts and targets cancer stem cells specifically from the heterogeneous cancer cell population using CCL20 as a marker. By identifying and isolating this specific subpopulation through CCL20 expression detection, the therapy can focus on eliminating the root cause of relapse and metastasis rather than treating all cancer cells uniformly

Inventive Principle:
Principle #2Taking out (Extraction)

Solution Approach 2:

The patent changes the therapeutic parameter from non-specific chemotherapy to CCL20-targeted therapy. By detecting and targeting cells with high CCL20 expression, the treatment shifts from a blanket approach to a precision approach that specifically addresses cancer stem cells while potentially sparing other cell types

Inventive Principle:
Principle #35Parameter changes

2Ease of operation

If surface marker phenotypes are used to identify cancer stem cells, then detection is simplified, but there is no consensus on reliable markers for human colorectal cancer stem cells

Engineering Contradiction:
Improvedetection simplicityVSAvoidmarker reliability
Core Design Contradiction:
Ease of operationVSMeasurement precision

Solution Approach 1:

The patent uses CCL20, a chemokine previously identified in other cancer types (breast, pancreatic, colorectal), as a surrogate marker for cancer stem cells in colorectal cancer. This copying approach from other validated cancer models provides a reliable detection method when direct colorectal CSC markers are not yet established

Inventive Principle:
Principle #26Copying

Solution Approach 2:

CCL20 serves multiple functions in this context: it acts as a detection marker for cancer stem cells, a therapeutic target for neutralizing antibodies, and a potential prognostic indicator. This multi-functionality simplifies the overall diagnostic and therapeutic workflow while maintaining precision

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

3Object-generated harmful factors

If cancer stem cells are targeted, then tumorigenicity and relapse are reduced, but current methods are inadequate in specifically targeting CSCs

Engineering Contradiction:
ImprovetumorigenicityVSAvoidtargeting specificity
Core Design Contradiction:
Object-generated harmful factorsVSMeasurement precision

Solution Approach 1:

The patent employs neutralizing antibodies that continuously block CCL20 function, preventing cancer stem cells from receiving survival and proliferation signals. This continuous inhibition ensures sustained targeting of CSCs throughout the therapeutic course, rather than transient effects

Inventive Principle:
Principle #20Continuity of useful action

Solution Approach 2:

CCL20 acts as an intermediary marker that connects the invisible cancer stem cell population to detectable and targetable signals. By focusing on CCL20 expression and function, the therapy indirectly targets CSCs through their unique secretory profile, enabling specific identification and intervention

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

This approach effectively identifies and inhibits CSCs, potentially leading to improved therapeutic outcomes by reducing tumorigenicity and enhancing disease remission and patient quality of life by targeting the CCL20-CCR6 axis.

Implementation Method 1

contacting the sample with an agent that binds to a CCL20 nucleic acid sequence or a CCL20 amino acid sequence; detecting the presence or absence of binding between the agent and the CCL20 nucleic acid sequence or the CCL20 amino acid sequence

Methodology Applied
Scientific EffectHybridization:

Implementation Method 2

In some embodiments, the agent may comprise an antibody that specifically binds to at least a portion of the CCL20 amino acid sequence

Methodology Applied
Scientific EffectAntibody binding:

Data Source

PatentEP3322484B1Method for detecting cancer stem cells
Publication Date: 2021.03.24 MEDIMMUNE LLC
  • EP3322484B1 patent drawingFigure 1A~1E
  • EP3322484B1 patent drawingFigure 2
  • EP3322484B1 patent drawingFigure 3A~3E

AI summary

The disclosure generally provides compositions and methods that are useful in the treatment of cancer. More specifically, the methods and compositions may be used to detect, quantify, inhibit, kill, differentiate, or eliminate cancer stem cells (CSCs) and may be used in the treatment of cancers associated with CSCs, and particularly cancers and CSCs that express CCL20 and/or CCR6.