Cell Surface Vimentin Antibody for Mesenchymal CTC Detection

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Solution Overview

Problem

Current methods for detecting circulating tumor cells (CTCs) are limited, as they primarily target epithelial CTCs, failing to detect mesenchymal and epithelial-mesenchymal transformed (EMT) CTCs, which are significant in cancer metastasis, due to the lack of effective biomarkers.

Innovation Solution

Development of a novel monoclonal antibody specific to cell surface vimentin (CSV) that can detect and isolate both non-epithelial and EMT CTCs, along with the use of phosphatase inhibitors to enhance vimentin expression on CTCs for improved detection and isolation.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Measurement precision

If current detection tools use EpCAM and cytokeratins as markers, then epithelial CTC detection is achieved, but mesenchymal and EMT CTCs are excluded

Engineering Contradiction:
ImproveCTC detection accuracyVSAvoidmarker applicability range
Core Design Contradiction:
Measurement precisionVSAdaptability or versatility

Solution Approach 1:

The patent develops a novel antibody marker that can detect multiple types of CTCs (epithelial, mesenchymal, and EMT) through a single universal marker system, replacing the need for multiple specialized markers. This multi-functional antibody expands the detection capability across different CTC subtypes while maintaining detection precision.

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

Solution Approach 2:

The invention identifies and targets a different molecular parameter (novel antibody epitope) on CTC surfaces that is expressed across diverse cancer types, including mesenchymal and EMT transformed cells. By changing the detection parameter from traditional epithelial markers to this novel marker, the system achieves broader adaptability without sacrificing detection accuracy.

Inventive Principle:
Principle #35Parameter changes

2Ease of operation

If traditional CTC detection methods are used, then detection simplicity is maintained, but detection sensitivity for rare CTCs is insufficient

Engineering Contradiction:
Improvedetection method simplicityVSAvoidCTC detection sensitivity
Core Design Contradiction:
Ease of operationVSMeasurement precision

Solution Approach 1:

The patent employs fluorescently labeled antibodies that bind to CTCs, enabling visual detection and differentiation of rare tumor cells from blood cells through fluorescence signals. This optical detection method maintains operational simplicity while dramatically improving sensitivity for detecting rare CTCs in large volumes of blood.

Inventive Principle:
Principle #32Color changes

Solution Approach 2:

The invention uses antibody-CTC complex formation where the antibody acts as a molecular copy or surrogate that binds specifically to CTC surface antigens. This molecular copying approach allows indirect detection and enrichment of rare CTCs while preserving the simplicity of the overall detection workflow.

Inventive Principle:
Principle #26Copying

3Adaptability or versatility

If novel vimentin-specific antibody is used, then detection of mesenchymal and EMT CTCs is improved, but device complexity increases

Engineering Contradiction:
ImproveCTC subtype detection rangeVSAvoiddetection system complexity
Core Design Contradiction:
Adaptability or versatilityVSDevice complexity

Solution Approach 1:

The patent employs a segmented detection approach where the novel vimentin-specific antibody is used in combination with existing detection platforms, dividing the detection task into specific antibody binding and standard detection steps. This segmentation allows the novel antibody to expand detection capability without requiring complete system redesign, thus limiting complexity increase.

Inventive Principle:
Principle #1Segmentation

Solution Approach 2:

The novel antibody serves as an intermediary molecule that bridges the gap between diverse CTC types and the detection system. By using this antibody as a mediator that binds to a common antigen across different CTC subtypes, the system achieves expanded adaptability while maintaining the existing detection infrastructure, thereby limiting complexity increases.

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

The antibody enables the specific detection and isolation of CTCs from both epithelial and non-epithelial cancers, enhancing early tumor detection, metastasis monitoring, and therapeutic evaluation, and can be used in conjunction with existing markers to improve the sensitivity and reliability of CTC detection methods.

Implementation Method 1

the antibody specifically binds to a vimentin polypeptide and wherein the antibody competes for binding of the polypeptide with an 84-1 monoclonal antibody

Methodology Applied
Scientific EffectAntibody-antigen binding:

Implementation Method 2

the use of phosphatase inhibitors to enhance vimentin expression on CTCs for improved detection and isolation

Methodology Applied
Scientific EffectPhosphatase inhibition:

Data Source

PatentEP2964672B1Specific detection tool for mesenchymal and epithelial-mesenchymal transformed circulating tumor cells
Publication Date: 2019.10.09 BOARD OF RGT THE UNIV OF TEXAS SYST
  • EP2964672B1 patent drawingFigure 1A
  • EP2964672B1 patent drawingFigure 1B
  • EP2964672B1 patent drawingFigure 1C

AI summary

The present invention includes the discovery of cell-surface vimentin as a novel biomarker to detect and isolate mesenchymal and epithelial-mesenchymal transformed circulating tumor cells from blood of cancer patients. In addition, an antibody specific for the detection of cell-surface vimentin on circulating tumor cells and the use the antibody to detect, enumerate, and isolate CTC are provided.