Biomarker Panel Predicts Cancer Immunotherapy Sensitivity
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Solution Overview
Problem
Current immunotherapy treatments for cancer, such as combination therapies using anti-PD1 and anti-CTLA4 monoclonal antibodies, face challenges in predicting patient responsiveness, leading to high costs, adverse events, and inefficacy in approximately 45% of advanced melanoma patients, necessitating a more personalized approach to identify suitable candidates.
Innovation Solution
The method involves determining the presence and expression levels of specific biomarkers like CD4+CD25highCD39high T cells, Granzyme B, and other cytokines in tumor samples to predict sensitivity or resistance to immunotherapy, allowing for personalized treatment decisions and reducing unnecessary exposure to costly and potentially harmful treatments.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Reliability
If combination immunotherapy (anti-PD1 and anti-CTLA4) is administered to all advanced melanoma patients, then overall survival benefits and durable remissions are achieved in responsive patients, but 45% of patients experience treatment inefficacy, high costs, and severe adverse events
Solution Approach 1:
The patent applies preliminary action by determining biomarker expression levels (PD-L1, TMB, CD8+ T-cell infiltration, tertiary lymphoid structures) before initiating combination immunotherapy. This pre-treatment assessment identifies responsive patients in advance, allowing clinicians to administer combination therapy only to those likely to benefit, while directing non-responders to alternative treatments, thereby preventing unnecessary adverse events and costs in 45% of patients who would not respond
Solution Approach 2:
The patent employs parameter changes by establishing specific quantitative thresholds for multiple biomarkers (e.g., PD-L1 expression levels, TMB cutoff values, CD8+ T-cell infiltration densities, TLS presence/absence). These parameter definitions enable objective classification of patients into responsive vs. non-responsive categories, transforming subjective treatment decisions into data-driven selections that optimize efficacy while minimizing harm
2Loss of information
If routine tumor biopsies are used for standard diagnostic purposes, then histological diagnosis and basic molecular profiling are obtained, but predictive information for immunotherapy response is insufficient
Solution Approach 1:
The patent applies merging by integrating multiple diagnostic assessments into a unified immunotherapy response prediction framework. Instead of treating biomarker evaluation as separate add-on tests, the patent combines PD-L1 IHC, TMB sequencing, CD8+ T-cell immunohistochemistry, and tertiary lymphoid structure morphological assessment into a coordinated diagnostic protocol that leverages the existing tumor biopsy specimen for comprehensive predictive profiling
Solution Approach 2:
The patent demonstrates universality by designing a multi-biomarker panel that can be applied across different cancer types and settings. The same framework of assessing PD-L1, TMB, CD8+ T-cells, and TLS can be used for both combination immunotherapy decision-making and potentially other immunotherapy regimens, making the diagnostic approach broadly applicable rather than disease-specific or treatment-specific
Data Source
AI summary
The present invention relates to a method of predicting, assessing or monitoring the sensitivity of a subject having a cancer to an immunotherapy, preferably to an immunotherapy combining at least two immunotherapeutic agents, and to corresponding kits and uses thereof. The method of predicting, assessing or monitoring the sensitivity of a subject having a tumor to an immunotherapy typically comprises a step of assessing, before any immunotherapeutic treatment step in the subject, the presence of CD4+CD25highCD39high T cells in a tumor sample of the subject, the presence of CD4+CD25highCD39high T cells in the tumor sample of the subject being indicative of sensitivity of the subject to the immunotherapy, and the absence of CD4+CD25highCD39high T cells in the tumor sample of the subject being indicative of resistance of the subject to the immunotherapy.