HDAC Expression Profiling for Immunotherapy Response Prediction
Find Innovative SolutionsGenerate Solutions
Solution Overview
Problem
Current anti-PD-L1/PD-1 immune checkpoint inhibitors show limited effectiveness in treating solid tumors, with only up to 20% of patients with advanced non-small cell lung cancer benefiting, and even lower response rates in other cancer types like breast, colon, and pancreatic cancers, leaving a significant unmet medical need.
Innovation Solution
A method involving assaying a subject's sample for expression of two or more Histone deacetylases (HDACs) to determine a response score, which predicts the effectiveness of combination immunotherapy and HDAC inhibitor therapy, and administering a therapeutically effective amount of both to the subject, specifically using HDAC1, HDAC2, HDAC3, HDAC4, HDAC5, and other HDACs to assess the ratio for treatment response.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Reliability
If immunotherapy alone is used to treat solid tumors, then treatment simplicity is maintained, but the response rate is limited to up to 20% of patients
Solution Approach 1:
The patent performs HDAC expression profiling and ratio calculation before initiating treatment to identify patients who will respond to combination therapy. This preliminary biomarker assessment enables selective enrollment of responsive patients into the combination therapy arm, thereby improving overall response rates while avoiding unnecessary complexity for non-responders
Solution Approach 2:
The patent combines immunotherapy with HDAC inhibitors to modify the biological parameters of the tumor microenvironment. By inhibiting HDACs, the treatment alters gene expression patterns, increases immune cell infiltration, and enhances tumor immunogenicity, thereby improving the response rate beyond what immunotherapy alone can achieve
2Reliability
If combination immunotherapy and HDAC inhibitor therapy is administered to all patients, then the response rate increases, but the treatment complexity and cost increase
Solution Approach 1:
The patent applies combination therapy selectively to specific patient subgroups based on their HDAC expression profiles. Patients with favorable HDAC ratios (indicating likely responsiveness) receive the full combination therapy, while others receive standard immunotherapy alone. This localized application of complex treatment to the appropriate patient population improves response rates without universally increasing treatment complexity
Solution Approach 2:
The patent segments the patient population into distinct groups based on HDAC expression patterns and ratios. By dividing patients into responders and non-responders based on biomarker profiling, the treatment strategy can be optimized for each segment, allowing combination therapy to be applied only where it will be most effective
3Measurement precision
If HDAC expression profiling is performed to identify responsive patients, then treatment precision is improved, but the diagnostic complexity increases
Solution Approach 1:
The patent extracts and measures the expression levels of specific HDAC isoforms (particularly HDAC1, HDAC2, HDAC3, HDAC4, and HDAC5) from tumor tissue samples. By focusing on a targeted panel of key HDAC markers rather than comprehensive genomic profiling, the diagnostic complexity is reduced while maintaining sufficient predictive accuracy for treatment response
Data Source
AI summary
Disclosed herein is a method for treating a solid tumor in a subject that involves assaying a sample from the subject for expression of two or more Histone deacetylases (HDACs); determining a response score from the expression of the two or more HDACs, wherein the response score predicts whether the subject will respond to combination immunotherapy and HDAC inhibitor therapy; and administering to the subject a therapeutically effective amount of a combination of immunotherapy and an HDAC inhibitor.