Nutritional Agents for T Cell Exhaustion Reduction
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Solution Overview
Problem
Current immunotherapies, such as checkpoint blockade therapy, show limited effectiveness in cancer treatment due to T cell exhaustion and immunosuppressive tumor microenvironments, necessitating the need for interventions that enhance T cell function and immune fitness.
Innovation Solution
The use of agents like nicotinamide riboside, vitamin B12, urolithin, manganese, serine, glycine, arginine, and asparagine, either alone or in combination, to boost T cell function and reduce exhaustion, particularly in adoptive T cell transfer protocols.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Reliability
If checkpoint blockade therapy is administered, then immune response is activated, but T cell exhaustion occurs reducing long-term effectiveness
Solution Approach 1:
The patent applies parameter changes by modifying the metabolic state of T cells through nutritional interventions. Specifically, it alters energy metabolism parameters (glycolysis vs oxidative phosphorylation) and mitochondrial function parameters to transition T cells from an exhausted state back to a functional state, thereby extending their operational lifespan while maintaining immune response effectiveness
Solution Approach 2:
The patent implements preliminary action by pre-treating T cells with nutritional agents (nicotinamide riboside, vitamin B12, urolithin A, manganese, serine, glycine, arginine, asparagine) before adoptive transfer. This preparatory metabolic conditioning enhances the cells' functional capacity and resistance to exhaustion prior to their introduction into the tumor microenvironment
2Strength
If T cells are activated to fight cancer, then tumor elimination capability increases, but energy metabolism becomes unsustainable leading to cell death
Solution Approach 1:
The patent changes energy metabolism parameters by inducing a metabolic switch in activated T cells. It promotes a transition from excessive glycolysis to a more sustainable balance involving oxidative phosphorylation and fatty acid oxidation, thereby maintaining tumor elimination capability while improving energy sustainability and preventing metabolic exhaustion
Solution Approach 2:
The patent introduces nutritional agents as intermediary substances that mediate between T cell activation and energy metabolism. These agents (particularly nicotinamide riboside as an NAD+ precursor and urolithin A as a mitophagy inducer) act as biochemical intermediaries to optimize mitochondrial function and energy production efficiency
3Reliability
If immunosuppressive microenvironment is present, then tumor survival is enhanced, but immune fitness deteriorates reducing therapy response
Solution Approach 1:
The patent applies preliminary action by pre-conditioning T cells with nutritional interventions before they encounter the immunosuppressive tumor microenvironment. This advance metabolic preparation enhances the cells' adaptability and resistance to suppressive conditions, allowing them to maintain immune fitness despite the challenging environment
Solution Approach 2:
The patent implements preliminary anti-action by pre-treating T cells with agents that counteract the effects of the immunosuppressive microenvironment. The nutritional interventions (particularly urolithin A for mitophagy and nicotinamide riboside for NAD+ replenishment) prepare the cells to resist exhaustion and maintain functionality before exposure to tumor-derived suppressive factors
Data Source
AI summary
An agent for use in reducing T cell exhaustion and/or increasing T cell function, and/or boosting immunity, wherein the agent is selected from the group consisting of nicotinamide riboside, vitamin B12, a urolithin, manganese, serine, glycine, arginine, asparagine, and a combination of two or more thereof.