MUC16 Immune Cell Binding Ovarian Cancer Detection

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Solution Overview

Problem

Current biomarkers for ovarian cancer, such as CA125, suffer from high false positives and lack specificity, making them unreliable for screening and monitoring, especially due to elevation in conditions like pregnancy and endometriosis, necessitating a more effective diagnostic method.

Innovation Solution

Measuring MUC16 bound to immune cells, specifically using flow cytometry to detect elevated levels on natural killer cell subsets CD16neg/CD56bright relative to CD16pos/CD56dim, and assessing Siglec-9 expression on these cells, provides a more sensitive and specific indicator of ovarian cancer and preeclampsia.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Reliability

If CA125 levels are measured in serum to monitor ovarian cancer, then the monitoring function is provided, but high false positives occur due to elevation in pregnancy and endometriosis

Engineering Contradiction:
Improvediagnostic reliabilityVSAvoidspecificity
Core Design Contradiction:
ReliabilityVSMeasurement precision

Solution Approach 1:

The invention segments the CA125 measurement approach by distinguishing between free CA125 in serum and CA125 bound to immune cells. This segmentation allows the patent to measure CA125 in a different context (bound to immune cells) that avoids the false positives associated with free CA125 measurement in serum, particularly during pregnancy and endometriosis.

Inventive Principle:
Principle #1Segmentation

Solution Approach 2:

The invention introduces immune cells as an intermediary medium for CA125 measurement. Instead of directly measuring free CA125 in serum, the patent measures CA125 that has bound to immune cells, using the immune cells as a mediator to achieve more specific detection of ovarian cancer while avoiding false positives from other conditions.

Inventive Principle:
Principle #24Intermediary (Mediator)

2Adaptability or versatility

If CA125 is used as a screening tool for the general population, then screening coverage is achieved, but the high false positive rate makes it unreliable

Engineering Contradiction:
Improvescreening applicabilityVSAvoiddiagnostic reliability
Core Design Contradiction:
Adaptability or versatilityVSReliability

Solution Approach 1:

The invention segments the diagnostic approach into two distinct measurements: free CA125 in serum and CA125 bound to immune cells. This segmentation enables the patent to use the bound CA125 measurement for reliable population screening while avoiding the false positives that plague free CA125 screening, thus maintaining screening applicability while improving diagnostic reliability.

Inventive Principle:
Principle #1Segmentation

3Measurement precision

If MUC16 is measured on immune cells to improve specificity, then diagnostic accuracy is enhanced, but the measurement complexity increases

Engineering Contradiction:
ImprovespecificityVSAvoidassay complexity
Core Design Contradiction:
Measurement precisionVSDevice complexity

Solution Approach 1:

The invention applies universality by using flow cytometry, a widely available and established technology, to perform the MUC16 measurement on immune cells. This approach leverages the existing multi-functionality of flow cytometry platforms to achieve enhanced specificity without requiring entirely new complex equipment or methodologies.

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

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 enhances diagnostic accuracy by distinguishing ovarian cancer from other conditions, allowing for better monitoring of disease progression and recurrence, and differentiating between ovarian cancer and preeclampsia.

Implementation Method 1

measuring the sample of immune cells from the subject for MUC16 bound to immune cells contained in the sample

Methodology Applied
Scientific EffectLight scattering: Scattering

Implementation Method 2

detecting the antibody specific for MUC16 and MUC16 bound to the immune cells

Methodology Applied
Scientific EffectFluorescence detection: Fluorescence

Implementation Method 3

an antibody specific for MUC16 is used to measure the level of MUC16 bound to the immune cells

Methodology Applied
Scientific EffectAntigen-antibody binding: Adsorption

Data Source

PatentUS8492104B2Methods and kits to detect and monitor ovarian cancer and preeclampsia
Publication Date: 2013.07.23 WISCONSIN ALUMNI RES FOUND
  • US8492104B2 patent drawing
  • US8492104B2 patent drawing
  • US8492104B2 patent drawing

AI summary

The present invention provides methods and kits related to a prognostic, and, in certain embodiments, diagnostic indicator for ovarian cancer which comprises measuring the level of MUC16 bound to immune cells. The level of MUC16 bound to immune cells can by itself be an indicator of disease regression or recurrence, or this indicator can be used in conjunction with assays for serum CA125 and other diagnostic markers. The invention further provides methods and kits related to the detection of ovarian cancer by measuring levels of Siglec-9 expression on immune cells. As well, related methodologies are provided for the detection of preeclampsia in pregnant human subjects.