Multiplexed Immune Scoring Algorithm for Tissue Infiltrating Lymphocytes
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Solution Overview
Problem
Current methods lack the ability to accurately quantify and score the immune response in cancer patients using tissue-infiltrating lymphocytes on a single slide, incorporating necessary immune markers, which is essential for predicting disease progression and treatment outcomes in melanoma and other cancers.
Innovation Solution
A multiplexed assay and digital scoring algorithm that simultaneously detects CD3, CD8, CD20, and FoxP3 markers in a tissue sample, along with a tumor marker, using an automated staining and imaging system to generate an immune score, enabling the assessment of immune cell types, density, and location within the tumor microenvironment.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Measurement precision
If traditional histopathological methods are used to examine tissue samples, then the examination can be performed using standard light microscopy equipment, but the ability to accurately quantify and score multiple immune markers simultaneously is limited
Solution Approach 1:
The patent divides the detection of multiple immune markers into separate detection steps, where each marker (CD3, CD8, CD20, FOXP3) is detected and visualized sequentially using different fluorescently-labeled antibodies. This segmentation allows accurate quantification of each marker while using a single imaging system rather than requiring multiple specialized devices.
Solution Approach 2:
The patent employs a universal imaging system that can detect multiple fluorescent channels, allowing a single device to perform the function of multiple specialized detectors. The system uses different excitation and emission wavelengths to simultaneously or sequentially detect multiple markers, reducing overall system complexity while maintaining measurement precision.
2Productivity
If multiple immune markers are detected on separate slides, then each marker can be detected with high specificity, but the productivity and efficiency of the assay is reduced
Solution Approach 1:
The patent merges the detection of multiple immune markers onto a single tissue slide by using multiplex immunofluorescence staining. Different antibodies labeled with distinct fluorophores are applied in a coordinated manner, allowing simultaneous detection of CD3, CD8, CD20, and FOXP3 markers on the same tissue section, thereby increasing productivity without compromising detection specificity.
Solution Approach 2:
The patent uses fluorophores as intermediaries that allow multiple markers to be detected simultaneously on a single slide. Each fluorophore has distinct excitation and emission properties, acting as a mediator that enables the imaging system to distinguish between different markers while maintaining high specificity for each target antigen.
3Measurement precision
If manual histopathological examination is used to assess immune infiltrates, then the method is simple and requires minimal equipment, but the objective quantification and scoring of immune cell populations is difficult
Solution Approach 1:
The patent replaces manual visual assessment with automated image analysis software that objectively quantifies immune cell populations. The system captures fluorescent images and uses computer algorithms to count and characterize cells expressing different markers, providing precise objective measurements while maintaining ease of operation through automated processing of the imaging data.
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 provides a more accurate prognostic tool for predicting patient survival and guiding treatment decisions by quantitatively analyzing immune cell populations, outperforming traditional histopathological methods in predicting disease-free survival and overall survival in colorectal cancer and potentially other malignancies.
Implementation Method 1
contacting the sample with specific binding moieties, wherein the specific binding moieties include a CD3 specific binding moiety, a CD8 specific binding moiety, a CD20 specific binding moiety, and a FoxP3 specific binding moiety
Implementation Method 2
A multiplex chromogen detection system is provided that enables the use of light microscopy to visually separate and identify multiple biomarkers in a tissue section.
Data Source
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Figure 2(A)~2(B)
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AI summary
This disclosure describes methods, kits, and systems for scoring the immune response to cancer through examination of tissue infiltrating lymphocytes (TILs). Methods of scoring the immune response in cancer using tissue infiltrating lymphocytes include detecting CD3, CD8, CD20, and FoxP3 within the sample and scoring the detection manually or scoring the digital images of the staining with the aid of image analysis and algorithms.