Pentanoate-Enhanced CAR T Cells for Stronger Effector Function
Find Innovative SolutionsGenerate Solutions
Solution Overview
Problem
The underlying mechanisms of how commensal bacteria enhance anti-tumor immunity through short-chain fatty acids (SCFAs) are not fully understood, and existing methods for activating immune cells for cellular immune therapy are limited in efficacy.
Innovation Solution
Incubating chimeric antigen receptor (CAR) T cells with short-chain fatty acids like pentanoate and butyrate to activate immune cells, enhancing the production of effector molecules and improving cellular immune therapy outcomes for cancer and infectious diseases.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Reliability
If immune cells are activated through conventional methods for cellular immune therapy, then immune cell function is improved, but the production of effector molecules and long-term persistence remain limited
Solution Approach 1:
The patent applies parameter changes by introducing short-chain fatty acids (pentanoate and butyrate) to alter the biochemical environment for T cell activation. These SCFAs modify epigenetic parameters through HDAC inhibition, leading to enhanced effector molecule production and improved therapeutic efficacy while maintaining T cell functionality.
Solution Approach 2:
The patent uses short-chain fatty acids as intermediary substances that mediate between the immune cells and the therapeutic outcome. These SCFAs act as molecular mediators that enhance T cell activation and effector function without directly being the therapeutic agent themselves, bridging the gap between conventional activation methods and improved efficacy.
2Productivity
If short-chain fatty acids are used to activate immune cells, then production of effector molecules increases, but the mechanism of action is not fully understood
Solution Approach 1:
The patent employs feedback mechanisms by measuring multiple parameters (effector molecule production, T cell persistence, HDAC activity) to understand and optimize the SCFA-mediated activation process. This systematic feedback approach helps elucidate the molecular mechanisms while continuously improving therapeutic outcomes.
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
Increased production of effector molecules such as CD25, IFN-γ, and TNF-α in immune cells, leading to improved anti-tumor immunity and enhanced therapeutic efficacy against established tumors.
Implementation Method 1
The short-chain fatty acid (SCFA) pentanoate enhances the function of CD8 +Tbx21, Ifnγ and Eomes, resulting in the enhanced production of effector molecules such as granzyme B and TNF-α in human and murine CTLs
Data Source
Figure 1A
Figure 1B
Figure 1C~1D
AI summary
The invention involves improving the cultivation of T cells by incubating them with short-chain fatty acid (SCFA) pentanoate after isolation from peripheral blood. The effect is that the cells are activated and the production of effector molecules is increased. This increases the chances of success of tumor therapy. This is5 illustrated by T-cells from mice that are transferred to mice with subcutaneous pancreatic tumors after the procedure. This type of cell treatment can be transferred to humans and the improved treatment of pancreatic cancer. We show in detail that the short-chain fatty acid (SCFA) pentanoate enhances the function of CD8+ cytotoxic T lymphocytes (CTLs). We show that Pentanoate promotes the core molecular signature of murine CD8+ CTLs. Pentanoate enhances anti-tumor activity of antigen-specific CTLs. Bacterial- derived SCFAs exhibit specific HDAC class I inhibitory activity. Pentanoate- producing bacteria enhance CD8+ T cell-mediated anti-tumor immune responses.