Patient Selection for HDAC Inhibitor Combination Therapy
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Solution Overview
Problem
There is a need for effective cancer immunotherapy, particularly for non-small cell lung cancer and melanoma, where the impact of HDAC inhibitors on cancer patient systemic immunity remains unclear, and there is a requirement for efficacious compounds and methods to treat these diseases, especially for patients who have progressed or were unresponsive to prior therapies.
Innovation Solution
A method involving the selection of patients for combination therapy using HDAC inhibitors and a second therapeutic agent based on the percentage of CD14-positive, HLA-DR-high, and/or CD16-negative cells in peripheral blood samples, where the percentage is greater than a predetermined threshold, to administer a combination therapy, potentially including entinostat and anti-PD-1 antibodies, to enhance treatment efficacy.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Reliability
If HDAC inhibitors are used to treat cancer, then tumor cell growth is inhibited and differentiation is promoted, but the impact on cancer patient systemic immunity remains unclear and may be detrimental
Solution Approach 1:
The patent changes the parameter of patient selection by measuring specific immune cell markers (CD14, HLA-DR, CD16) before treatment. By stratifying patients based on their baseline immune phenotype parameters, the system identifies those who are likely to benefit from HDAC inhibitor therapy while avoiding those who may experience detrimental immune suppression.
Solution Approach 2:
The patent implements feedback by monitoring immune cell parameters during treatment and using this information to adjust therapy decisions. The assessment of immune cell markers provides feedback about the patient's immune status, allowing clinicians to determine whether to proceed with HDAC inhibitor treatment or modify the treatment approach based on the patient's immune response.
2Reliability
If combination therapy with HDAC inhibitors and immune checkpoint inhibitors is administered, then treatment efficacy is improved, but patient selection becomes more complex requiring multiple biomarker measurements
Solution Approach 1:
The patent segments the patient population into distinct groups based on their immune cell phenotype markers. By dividing patients into subgroups with specific marker profiles (e.g., CD14+, HLA-DRhigh, CD16- monocytes), the system simplifies the selection process while maintaining the benefits of combination therapy. This segmentation allows for targeted treatment assignment based on predicted response.
Solution Approach 2:
The patent uses immune cell marker measurements as intermediary biomarkers to bridge the gap between treatment administration and efficacy assessment. These markers serve as mediators that predict treatment response without requiring direct measurement of treatment effect, simplifying the overall selection process while maintaining high predictive accuracy.
3Reliability
If patients with high percentage of CD14-positive, HLA-DR-high, and/or CD16-negative cells are selected for combination therapy, then response to treatment is improved, but the selection process requires sophisticated flow cytometry analysis
Solution Approach 1:
The patent replaces complex multi-parameter analysis with a focused measurement approach using flow cytometry to detect specific immune cell markers (CD14, HLA-DR, CD16). By substituting comprehensive immune profiling with targeted marker detection, the system maintains high predictive accuracy while simplifying the measurement process and reducing technical complexity.
Data Source
AI summary
Described herein are methods for selecting cancer patients for treatment with a combination therapy comprising an HDAC inhibitor and a second therapeutic agent. In particular, methods are provided for the examination of a non-cancer cell type which are CD14-positive, HLA-DR-high and/or CD16-negative, as a therapeutic indicator in the setting of HDAC inhibitor combination therapies.