Lectin-Bound Extracellular Vesicle Detection for Pancreatic Cancer

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Solution Overview

Problem

Current methods for detecting pancreatic cancer, particularly through liquid biopsies, face challenges in specificity and sensitivity, making it difficult to detect early-stage pancreatic cancer effectively.

Innovation Solution

A method involving the use of extracellular vesicles from body fluid samples interacting with specific lectins, such as DSA, STL, LEL, ACA, UDA, ABA, MAH, and TJA-1, followed by measurement and evaluation using antibodies binding to pan-extracellular vesicle membrane proteins like CD9, CD63, and CD81, to assess pancreatic cancer presence.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Measurement precision

If existing tumor markers (CA19-9, CEA, etc.) are used for liquid biopsy, then the sensitivity for detecting pancreatic cancer is improved, but the specificity decreases leading to high pseudopositive rate

Engineering Contradiction:
Improvedetection sensitivityVSAvoidspecificity
Core Design Contradiction:
Measurement precisionVSReliability

Solution Approach 1:

The invention segments the detection approach by separating the measurement into two distinct components: (1) quantifying total extracellular vesicle concentration as a marker of cancer burden, and (2) determining the glycosylation phenotype (sialylated vs. non-sialylated) of these vesicles. This segmentation allows each measurement to contribute differently to the diagnostic conclusion, improving both sensitivity and specificity compared to using single tumor markers.

Inventive Principle:
Principle #1Segmentation

Solution Approach 2:

The invention changes the detection parameter from measuring protein tumor markers (CA19-9, CEA) to measuring glycosylation patterns on extracellular vesicle surfaces. By using lectins that specifically bind to sialic acid residues, the method detects a different biochemical parameter that is more specific to pancreatic cancer, thereby reducing pseudopositive rates while maintaining sensitivity.

Inventive Principle:
Principle #35Parameter changes

2Measurement precision

If existing tumor markers are used for liquid biopsy, then early-stage pancreatic cancer detection is attempted, but the positive predictive value remains low especially for small tumors

Engineering Contradiction:
Improveearly detection capabilityVSAvoidpositive predictive value
Core Design Contradiction:
Measurement precisionVSReliability

Solution Approach 1:

The invention changes the detection parameter from protein tumor markers to glycosylation patterns on extracellular vesicles. The use of sialic acid-specific lectins detects a biochemical feature that is more specifically altered in pancreatic cancer cells, enabling earlier detection with higher positive predictive value even for small tumors where traditional markers fail.

Inventive Principle:
Principle #35Parameter changes

Solution Approach 2:

The invention introduces extracellular vesicles as an intermediary between pancreatic cancer cells and the detection system. These vesicles carry characteristic glycosylation patterns on their surface that reflect the cancer cell's state, serving as a more reliable intermediary marker than soluble tumor markers, thereby improving early detection accuracy and positive predictive value.

Inventive Principle:
Principle #24Intermediary (Mediator)

3Measurement precision

If invasive methods like EUS-FNA are used for tissue collection, then diagnostic accuracy is improved, but invasiveness and risk of seeding increase

Engineering Contradiction:
Improvediagnostic accuracyVSAvoidinvasiveness and seeding risk
Core Design Contradiction:
Measurement precisionVSObject-affected harmful factors

Solution Approach 1:

The invention extracts the diagnostic information from the cancer cells themselves by detecting characteristic extracellular vesicles in the blood, rather than extracting tissue through invasive procedures. This extraction approach obtains sufficient diagnostic material (vesicles in milliliters of blood) without the need for invasive tissue sampling, thereby eliminating invasiveness and seeding risks while maintaining diagnostic accuracy.

Inventive Principle:
Principle #2Taking out (Extraction)

Solution Approach 2:

The invention uses extracellular vesicles as an intermediary that carries diagnostic information from the cancer cells to the detection system in the bloodstream. These vesicles serve as a non-invasive surrogate for direct tissue sampling, providing the same diagnostic value as tissue biopsies without the harmful effects of invasiveness and seeding risk.

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 enables early detection of pancreatic cancer and monitoring of therapeutic effects with improved specificity and sensitivity, facilitating non-invasive and accurate diagnosis.

Implementation Method 1

bringing extracellular vesicles, which are in a body fluid sample derived from a subject, into contact with one or more kinds of lectins

Methodology Applied
Scientific EffectLectin-sugar chain recognition:

Implementation Method 2

measuring an amount of the extracellular vesicles bound to the one or more kinds of lectins after (a)

Methodology Applied
Scientific EffectAntibody-antigen binding:

Data Source

PatentUS11867697B2Pancreatic cancer detection method and pancreatic cancer detection kit
Publication Date: 2024.01.09 JVC KENWOOD CORP
  • US11867697B2 patent drawing
  • US11867697B2 patent drawing
  • US11867697B2 patent drawing

AI summary

A pancreatic cancer detection method is provided, including: (a) bringing extracellular vesicles, which are in a body fluid sample derived from a subject into contact with one or more kinds of lectins; (b) measuring an amount of the extracellular vesicles bound to the one or more kinds of lectins after (a); and (c) evaluating the presence of pancreatic cancer in the subject based on the amount of the extracellular vesicles measured in (b). In addition, a pancreatic cancer detection kit is provided, including: a solid-phase carrier on which one or more kinds of lectins are immobilized; and an antibody specifically binding to a pan-extracellular vesicle membrane protein or an antigen-binding fragment thereof.