Chidamide-Celecoxib Combination for Tumor Microenvironment Modulation
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Solution Overview
Problem
Current cancer immunotherapy strategies face challenges with immune escape mechanisms in the tumor microenvironment, leading to unsatisfactory efficacy and drug resistance, necessitating improved methods to regulate and enhance the immune response.
Innovation Solution
A combination of chidamide and celecoxib in specific salt forms, administered alone or with immune checkpoint inhibitors, to modulate the tumor microenvironment and boost anti-cancer activity.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Reliability
If immune checkpoint inhibitors are used for cancer treatment, then immune response is enhanced, but drug resistance occurs and efficacy is limited to 20-30% of patients
Solution Approach 1:
The patent combines chidamide (an HDAC inhibitor) with celecoxib (an NSAID) to create a synergistic combination therapy. This merging of two different drug mechanisms addresses drug resistance by attacking multiple pathways simultaneously, thereby improving the reliability of cancer treatment while overcoming the limitation of single-agent immunotherapy efficacy.
Solution Approach 2:
The invention creates a composite therapeutic regimen comprising chidamide, celecoxib, and immune checkpoint inhibitors. This composite approach integrates multiple pharmacological agents with different mechanisms of action to enhance overall treatment efficacy and overcome adaptive resistance, transforming the limited single-agent therapy into a multi-component solution that addresses both immune enhancement and resistance prevention.
2Reliability
If tumor microenvironment is not regulated, then immune escape mechanisms persist, but regulating it requires complex combination therapy
Solution Approach 1:
The chidamide-celecoxib combination serves multiple functions simultaneously: chidamide regulates epigenetic modifications to enhance immune recognition, while celecoxib modulates inflammatory pathways and cytokine production. This multi-functionality allows the combination to address various aspects of tumor microenvironment regulation without requiring separate interventions for each mechanism, thereby managing complexity while improving immune control.
3Ease of operation
If monotherapy with immune checkpoint inhibitors is used, then treatment simplicity is maintained, but response rate is limited to 20-30%
Solution Approach 1:
The patent merges immune checkpoint inhibitors with the chidamide-celecoxib combination to create a multi-agent regimen that maintains operational simplicity through standardized administration while dramatically improving response rates. The combination therapy addresses drug resistance and enhances immune activation, transforming the limited 20-30% response rate of monotherapy into a more effective multi-component solution.
Data Source
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AI summary
The present invention provides a combination of a histone deacetylase (HDAC) inhibitor, chidamide in an acidic salt form, and a nonsteroidal anti-inflammatory drugs (NSAIDs), celecoxib in a basic salt form. The present invention also provides methods which significantly regulate tumor microenvironment and therefore dramatically improve anti-cancer activity.