L-Arginine Modulation of T Cell Metabolism for Persistence
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Solution Overview
Problem
Current T cell-based immunotherapies face challenges due to the short persistence of antigen-specific T cells in patients, leading to rapid clearance after re-introduction, and reliance on cytokines or co-stimulatory molecules that can cause severe side effects.
Innovation Solution
The use of L-arginine and its ligands, such as BAZ1B, PSIP1, and TSN, to modulate T cell metabolism and survival, enhancing the generation of central memory-like T cells with enhanced anti-tumor activity by interacting with transcriptional regulators, thereby promoting T cell survival and persistence.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Duration of action of stationary object
If cytokines or co-stimulatory molecules are administered to promote T cell survival and persistence, then T cell persistence is improved, but severe side effects occur in the treated patient
Solution Approach 1:
The invention changes the metabolic parameter of T cells by modulating the mTOR pathway and amino acid metabolism, specifically through controlling nutrient availability and metabolic state to enhance T cell persistence without using cytokines or co-stimulatory molecules that cause side effects
Solution Approach 2:
The invention enables T cells to self-regulate their survival and persistence through metabolic adaptation and mTOR pathway activation, eliminating the need for external cytokine support and reducing dependence on immunosuppressive regimens
2Quantity of substance
If conventional T cell therapy protocols are used, then T cell re-introduction is achieved, but rapid clearance of T cells occurs after re-introduction
Solution Approach 1:
The invention applies preliminary metabolic conditioning and mTOR pathway modulation to T cells before re-introduction, preparing them for enhanced survival and persistence in the patient environment, thereby preventing rapid clearance after re-introduction
Solution Approach 2:
The invention changes physiological parameters of T cells including metabolic state, amino acid uptake, and mTOR pathway activity to improve their resilience and persistence following re-introduction into the patient
Data Source
AI summary
The present invention provides novel uses and methods for T cell based immunotherapies. Specifically, the invention relates to novel ligands, targets and nucleic acids and vectors encoding said targets that are useful for modulating T cell responses.