Patient Selection via Myeloid-Derived Suppressor Cell Ratios
Find Innovative SolutionsGenerate Solutions
Solution Overview
Problem
Current methods for selecting cancer patients for combination therapy lack effective predictive and prognostic biomarkers, particularly in relation to the levels of non-tumor myeloid-derived suppressor cells, which are crucial for determining the efficacy of therapies like entinostat and anti-PD-1/anti-PD-L1 antibodies.
Innovation Solution
The method involves measuring the ratio of myeloid-derived suppressor cells to peripheral blood mononuclear cells, or specific cell surface marker ratios like CD14-positive and HLA-DR-(lo/negative) cells, in peripheral blood samples to determine the suitability of patients for combination therapies involving entinostat and second therapeutic agents such as anti-PD-1 or anti-PD-L1 antibodies.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Reliability
If combination therapy with entinostat and second therapeutic agent is administered to all cancer patients, then some patients may benefit from enhanced treatment efficacy, but unnecessary side effects and treatment costs are incurred for patients who would not respond
Solution Approach 1:
The patent applies preliminary action by measuring the MDSC to PBMC ratio in peripheral blood samples before initiating combination therapy to identify patients who are most likely to respond. This pre-screening approach allows clinicians to select appropriate candidates for entinostat-based combination therapy, ensuring that only patients with favorable biomarker profiles (specific ratio ranges) receive the treatment, thereby avoiding unnecessary side effects in non-responders while maintaining high efficacy in selected patients
2Ease of operation
If current conventional treatment methods are used without biomarker selection, then treatment protocols are simple to implement, but treatment efficacy is reduced due to inability to identify responsive patients
Solution Approach 1:
The patent replaces the conventional mechanical/physical approach of universal treatment administration with a biomarker-based selection system. By measuring the MDSC to PBMC ratio in peripheral blood samples, the invention substitutes arbitrary or experience-based treatment decisions with an objective, quantifiable biomarker assessment. This substitution enables precise identification of patients who will respond to combination therapy, significantly improving treatment efficacy while maintaining operational simplicity through standardized blood sample analysis and ratio calculation
3Reliability
If biomarker analysis is performed to select patients for combination therapy, then treatment efficacy is improved through personalized medicine, but diagnostic complexity and testing requirements increase
Solution Approach 1:
The patent extracts the critical diagnostic information needed for patient selection by measuring specific cell populations (MDSC and PBMC) in peripheral blood samples and calculating their ratio. This extraction approach focuses on obtaining only the essential biomarker data (the MDSC to PBMC ratio) required for treatment decision-making, rather than performing comprehensive genomic or proteomic profiling. The method uses flow cytometry or similar techniques to isolate and quantify these specific cell types, thereby simplifying the diagnostic process while maintaining high treatment efficacy through accurate patient stratification
Data Source
AI summary
Described herein are methods for selecting cancer patients for treatment with a combination therapy comprising entinostat and a second therapeutic agent. In particular, methods are provided for the examination of a non-cancer cell type, myeloid-derived suppressor cells, e.g., those which are CD14-positive and HLA-DR-(lo/negative), as a therapeutic indicator in the setting of entinostat combination therapies.