Immune Gene Panel Predicts NSCLC Immunotherapy Response
Find Innovative SolutionsGenerate Solutions
Solution Overview
Problem
Current immunotherapy treatments for non-small cell lung cancer (NSCLC) face challenges in predicting responsiveness, with only 15-30% of patients responding to immune checkpoint inhibitors, and a need to differentiate between responders and non-responders to avoid adverse events and therapeutic resistance.
Innovation Solution
A method involving the measurement of specific gene expressions associated with immune activation and inhibition to predict responsiveness to immunotherapy, where the expression of 15 or more immune activation genes and 10 or less immune inhibition genes are upregulated, guiding the administration of immunotherapy such as anti-PD-1 or anti-PD-L1 antibodies like pembrolizumab, nivolumab, or atezolizumab.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Reliability
If immune checkpoint inhibitors are administered to all NSCLC patients, then some patients may experience therapeutic benefit, but many patients will experience treatment-related adverse events or therapeutic resistance without benefit
Solution Approach 1:
The patent segments the complex immune response into discrete gene expression categories (immune activation genes vs. immune inhibition genes), allowing systematic assessment of 20+ individual genes to predict immunotherapy response. This segmentation transforms an complex biological process into measurable, countable units that can be systematically evaluated.
Solution Approach 2:
The patent changes the parameter from simple PD-L1 expression level to a composite score based on differential expression of multiple immune-related genes. By measuring the net difference between immune activation and immune inhibition gene expressions, the method transforms a single-parameter assessment into a multi-parameter evaluation that better predicts therapeutic response.
2Reliability
If PD-L1 expression is used as a standalone biomarker, then the assessment is simple, but it fails to accurately predict response since PD-L1 negative tumors may also respond to immunotherapy
Solution Approach 1:
The patent merges multiple gene expression measurements into a unified predictive framework. By combining the expression levels of 15+ immune activation genes and 10+ immune inhibition genes into a single net immune score, the method integrates complex molecular information into one actionable metric that maintains predictive accuracy while simplifying clinical interpretation.
Solution Approach 2:
The patent creates a universal biomarker panel that can assess multiple aspects of immune tumor microenvironment simultaneously. The same gene expression profile serves multiple functions: predicting response to checkpoint inhibitors, identifying patients at risk of adverse events, and potentially guiding combination therapy decisions, making the assay multi-functional rather than limited to a single prediction.
Data Source
AI summary
The present disclosure provides methods for treating non-small cell lung cancer (NSCLC) in a subject in need thereof by obtaining a biological sample from the NSCLC from the subject; measuring the expression of the following genes associated with immune activation in the biological sample: IFNGR2, MICB, MICA, STATE, IFIT1, IFIT2, IFIT3, IFNGR1, IL16, STAT4, STAT5A, STAT2, SOCS5, STAT3, TNFSF4, TNFRSF18, CXCL9, IFNG, STAT1, TNFRSF9, CXCL10, SOCS1, TNFRSF4, SOCS3, CCL2, CD28, CD40, OX40, 4-1BB, GITR, CD27, ICOS, CD226, B7, CD226, TCR, and CD40L; measuring the expression of the following genes associated with immune inhibition in the biological sample: ES, CD86, HAVCR2, LAGS, PDCD1, TBX21, TNFRSF14, IDO1, PDCD1LG2, CD47, VTCN1, CD274, MIF, CD276, LGALS3, CTLA4, PD1, TIM3, BTLA, TIGIT, CD96, H3, VISTA, CD112R, and GITR; determining that the NSCLC is responsive to an immunotherapy where the expression of fifteen or more of the genes associated with immune activation are upregulated and ten or less of the genes associated with immune inhibition are upregulated; and administering an immunotherapy to the subject where the subject is determined to be responsive to the immunotherapy.