Immune Response Score Method Using RNA-Seq Gene Expression

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Solution Overview

Problem

Current methods for analyzing immune cell infiltration in tumors, such as immunohistochemical (IHC) staining, are complex and variable, leading to inconsistent results due to protocol variability and intra-tumoral heterogeneity, making it difficult to accurately predict patient response to immunotherapy.

Innovation Solution

A method to determine an immune response score (irScore) by analyzing the expression of genes involved in anti-tumor immune cell signaling and immunosuppression in biological samples, using a targeted RNA-seq immune panel to classify samples into high or low immune infiltration groups, and predicting patient responsiveness to anticancer immunotherapies like Nivolumab and Pembrolizumab.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Measurement precision

If immunohistochemical (IHC) staining is used to analyze immune cell infiltration, then immune cell types can be identified, but the complexity of the analysis and protocol variability lead to inconsistent results

Engineering Contradiction:

Improveconsistency of immune cell infiltration measurementVSAvoidcomplexity of IHC analysis protocol

Core Design Contradiction:

Measurement precisionVSDevice complexity

Solution Approach 1:

The patent replaces the mechanical/IHC-based staining system with a molecular biology approach using RNA sequencing to detect immune cell infiltration through gene expression profiles. This substitution eliminates the complexity of IHC protocols while providing more consistent and reproducible measurements of immune cell infiltration in tumor samples.

Inventive Principle:

Principle #28Mechanics substitution (Replace mechanical system)

Solution Approach 2:

The patent changes the measurement parameter from physical staining intensity (IHC) to molecular gene expression levels (RNA-seq). By measuring the expression of immune-related genes rather than relying on staining protocols, the system achieves more precise and consistent quantification of immune cell infiltration without being affected by protocol variability.

Inventive Principle:

Principle #35Parameter changes

2Measurement precision

If multiple immune cell types are analyzed using IHC, then comprehensive immune profiling is achieved, but intra-tumoral heterogeneity and qualitative criteria lead to variable results

Engineering Contradiction:

Improveaccuracy of immune infiltration assessmentVSAvoidreliability of treatment response prediction

Core Design Contradiction:

Measurement precisionVSReliability

Solution Approach 1:

The patent replaces qualitative IHC assessment with quantitative RNA sequencing analysis. This molecular approach provides objective, quantifiable gene expression data that reliably captures immune cell infiltration across different tumor regions, eliminating the subjectivity and heterogeneity issues inherent in qualitative IHC scoring.

Inventive Principle:

Principle #28Mechanics substitution (Replace mechanical system)

Solution Approach 2:

The patent creates a universal gene expression-based assay that can simultaneously profile multiple immune cell types and their functional states in a single analysis. This multi-functional approach provides comprehensive immune profiling that is consistent across different tumor types and patients, improving both measurement precision and treatment prediction reliability.

Inventive Principle:

Principle #6Universality (Multi-functionality)

3Measurement precision

If specialized protocols and training are required for IHC analysis, then accurate staining can be achieved, but the barrier to widespread implementation increases

Engineering Contradiction:

Improveaccuracy of immune cell identificationVSAvoidease of implementing the assay

Core Design Contradiction:

Measurement precisionVSEase of manufacture

Solution Approach 1:

The patent replaces the skill-intensive IHC staining process with a molecular biology-based RNA sequencing approach. This substitution eliminates the need for specialized staining protocols and trained technicians while maintaining high measurement precision through automated, standardized molecular analysis procedures that can be implemented more broadly.

Inventive Principle:

Principle #28Mechanics substitution (Replace mechanical system)

Data Source

PatentUS10851422B2Methods of determining an immune response score

Publication Date: 2020.12.01 AMERICAN MOLECULAR LABORATORIES INC

AI summary

The present disclosure provides method for determining an immune response score (irScore), the method comprising: determining a number of differentially expressed genes that have are implicated in anti-tumor immune cell signaling/activation; determining a number of differentially expressed genes that are implicated in immunosuppression, wherein the irScore=X(low, medium, or high), wherein X is the number of differentially expressed genes that are implicated in anti-tumor immune cell signaling/activation, and wherein low refers to 1-4 differentially expressed genes that are implicated in immunosuppression, medium refers to 5-9 differentially expressed genes that are implicated in immunosuppression, and high refers to 10 or more differentially expressed genes that are implicated in immunosuppression.