Class I HDAC Inhibitors for Tumor Microenvironment Immunomodulation
Solution Overview
Problem
Current immunotherapy treatments for cancer, such as immune checkpoint inhibitors, face challenges with immune-related adverse events and low response rates due to the complex tumor microenvironment, where immunosuppressive cells inhibit cytotoxic T lymphocyte activity, and there is a need for compounds that can modulate the tumor microenvironment to enhance anti-tumor immunity.
Innovation Solution
Development of class I HDAC inhibitor compounds that epigenetically immunomodulate the tumor microenvironment by upregulating antigen processing and presentation, inducing histone H3 acetylation, activating cytotoxic T lymphocytes, and reducing immunosuppressive cells, thereby enhancing anti-tumor immune responses.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Reliability
If immune checkpoint inhibitors are used for cancer treatment, then immune activation is increased, but immune-related adverse events occur and response rate remains low
Solution Approach 1:
The patent introduces histone deacetylase inhibitors as intermediary compounds that modify the tumor microenvironment through epigenetic mechanisms. These inhibitors serve as mediators between the immune system and tumor cells, upregulating antigen presentation and modulating immune cell function without directly activating immune checkpoints, thereby reducing adverse events while maintaining therapeutic efficacy
Solution Approach 2:
The patent employs histone deacetylase inhibitors to change the epigenetic parameters of tumor cells and immune cells in the tumor microenvironment. By modifying histone acetylation levels, the treatment alters gene expression patterns to enhance antigen presentation and immune cell activation, achieving therapeutic benefit with improved safety profile
2Reliability
If immune checkpoint inhibitors are used for cancer treatment, then immune activation is increased, but response rate remains low due to complex tumor microenvironment
Solution Approach 1:
The patent introduces histone deacetylase inhibitors as intermediary compounds that modify the tumor microenvironment through epigenetic mechanisms. These inhibitors serve as mediators between the immune system and tumor cells, upregulating antigen presentation and modulating immune cell function without directly activating immune checkpoints, thereby reducing adverse events while maintaining therapeutic efficacy
Solution Approach 2:
The patent employs histone deacetylase inhibitors to change the epigenetic parameters of tumor cells and immune cells in the tumor microenvironment. By modifying histone acetylation levels, the treatment alters gene expression patterns to enhance antigen presentation and immune cell activation, achieving therapeutic benefit with improved safety profile
3Reliability
If immunosuppressive cells infiltrate the tumor microenvironment, then tumor growth is suppressed, but cytotoxic T lymphocyte activity is inhibited
Solution Approach 1:
The patent converts the immunosuppressive tumor microenvironment into a beneficial setting for anti-tumor immunity. By using histone deacetylase inhibitors to reverse epigenetic silencing of immune-related genes, the treatment transforms the previously harmful immunosuppressive milieu into an immunostimulatory environment that enhances CTL activity while maintaining the presence of immunosuppressive cells
Solution Approach 2:
The patent employs histone deacetylase inhibitors to change the epigenetic parameters of tumor cells and immune cells in the tumor microenvironment. By modifying histone acetylation levels, the treatment alters gene expression patterns to enhance antigen presentation and immune cell activation, achieving therapeutic benefit with improved safety profile
Applied Scientific Principles
This section explains which scientific principles are used to turn an abstract innovation direction into a practical engineering solution.
Function Achieved in This Case
The compounds effectively induce cell cycle arrest and apoptosis of tumor cells, activate immune memory, and modulate the tumor microenvironment to enhance immune responses, improving therapeutic efficacy against cancer.
Implementation Method 1
inducing histone H3 acetylation
Implementation Method 2
class I HDAC inhibitor compounds that epigenetically immunomodulate
Data Source
Figure 1~2(a)
Figure 2(b)~2(c)
Figure 2(d)~2(e)
AI summary
Provided are compounds class I HDAC inhibitors, their production and applications. The compounds possess epigenetic immunomodulatory activities in the tumor microenvironment (TME) and thus inhibit growth of tumor cells.