ICBT Response Prediction Using Gene Expression Panels
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Solution Overview
Problem
Current methods for predicting patient response to immune checkpoint blockade therapy in metastatic melanoma are inadequate, with existing biomarkers lacking validation and leading to unnecessary toxicity and ineffective therapy continuation.
Innovation Solution
A method involving the detection of gene panel transcription, expression, and activity levels, including Ribosomal biogenesis, TCR signaling, Cilia, Interferon pathway, Cell Cycle, Jak/Stat Signaling, and T cell/Immune tolerance clusters, to predict patient responsiveness to immune checkpoint blockade therapy.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Reliability
If tissue-based predictive biomarkers (PDL1 expression, tumor mutational burden) are used, then prediction capability is provided, but validation status is insufficient and reliability is poor
Solution Approach 1:
The patent uses liquid biopsy (circulating tumor DNA) as a non-invasive copy of the tumor genome, replacing the need for tissue biopsies. This copying approach enables repeated measurements from the same patient sample over time, improving both reliability through validation and measurement precision through serial monitoring of biomarker dynamics.
Solution Approach 2:
The patent transitions from static tissue biomarkers to dynamic liquid biomarkers that can be measured repeatedly. By monitoring changes in biomarker parameters over time (parameter changes), the system improves prediction accuracy and enables real-time assessment of treatment response, thereby enhancing both reliability and measurement precision.
2Object-affected harmful factors
If ICBT is applied to all patients, then treatment coverage is maximized, but unnecessary toxicity occurs in non-responders
Solution Approach 1:
The patent applies preliminary biomarker testing before initiating ICBT to identify patients likely to respond. This preliminary action filters out non-responders before treatment starts, preventing unnecessary toxicity while maintaining high treatment effectiveness in the selected responder population.
Solution Approach 2:
The patent implements feedback through serial biomarker measurements during treatment to monitor response in real-time. This feedback mechanism allows dynamic adjustment of treatment decisions, stopping ICBT in non-responders to avoid further toxicity while continuing it in responders to maintain effectiveness.
3Loss of time
If radiological response evaluation is performed at 12 weeks, then standard protocol is followed, but therapy discontinuation occurs prematurely and response is equivocal
Solution Approach 1:
The patent performs preliminary biomarker assessments at multiple time points before the standard 12-week radiological evaluation. This preliminary action provides earlier and more reliable response information, eliminating the need to wait for equivocal radiological results and preventing premature therapy discontinuation.
Solution Approach 2:
The patent replaces the mechanical/radiological response evaluation system with a molecular biomarker-based assessment system. This substitution enables earlier, more accurate, and less equivocal response detection through direct measurement of treatment effect on tumor DNA, eliminating the time delay and ambiguity of radiological imaging.
4Object-affected harmful factors
If non-invasive liquid biomarkers are used, then patient safety is improved, but measurement precision and validation are insufficient
Solution Approach 1:
The patent optimizes liquid biomarker parameters including sensitivity thresholds, dynamic range, and temporal resolution. By carefully adjusting these parameters and establishing validated measurement protocols, the system achieves both non-invasive sampling and high measurement precision, resolving the contradiction between safety and accuracy.
Data Source
AI summary
The present invention relates to methods for determining or predicting if a patient having a predetermined disease, for example cancer, in particular metastatic melanoma, is responsive, or will respond to a treatment based on immune checkpoint inhibitor. The present invention also relates to computer-implemented methods for implementing said methods and to kits.