Inhibiting RNA-Binding Proteins to Enhance CTL Activation
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Solution Overview
Problem
Current adoptive cell therapies, such as those using chimeric antigen receptor (CAR) T cells, are often ineffectual in many cancers due to limitations in the effector functions of cytotoxic T lymphocytes (CTLs), and there is a need to enhance these functions without toxic side effects.
Innovation Solution
Inhibiting or reducing the activity of post-transcriptional regulators of gene expression, specifically RNA-binding proteins like ZFP36 and ZFP36L1, to enhance CTL activation and proliferation, thereby increasing their cytotoxic activity and reducing the requirement for co-stimulation.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Reliability
If adoptive cell therapy using CAR T cells is applied, then targeted tumour therapy is achieved, but the effector functions of CTLs are limited making them ineffectual in many cancers
Solution Approach 1:
The patent changes the regulatory parameters of CTL gene expression by inhibiting post-transcriptional regulators (such as ZFP36, ZFP36L1, and other RNA-binding proteins). This modulation of transcriptional control parameters leads to enhanced effector function output including increased production of cytotoxic proteins and effector cytokines, thereby resolving the contradiction between therapy reliability and productivity
2Productivity
If CTL activation is enhanced through inhibition of post-transcriptional regulators, then effector function is improved, but the mechanism complexity increases
Solution Approach 1:
The patent extracts and targets specific post-transcriptional regulators (such as ZFP36, ZFP36L1, and other identified RNA-binding proteins) that are responsible for suppressing CTL effector function. By removing or inhibiting these specific regulatory components, the complex regulation mechanism is simplified, allowing enhanced effector function output without proportionally increasing overall system complexity
Data Source
AI summary
The invention relates to a method of enhancing cytotoxic T lymphocyte (CTL) activation and/or proliferation comprising inhibiting or reducing the activity of one or more post-transcriptional regulators of gene expression. Examples of such post-transcriptional regulators include RNA-binding proteins. Also provided is a CTL with enhanced activity and/or proliferative capacity obtainable by the methods defined herein, and a method of treating a disease or disorder in a subject in need thereof comprising administering said CTL with enhanced activity and/or proliferative capacity.