Epigenetic T Cell Editing for ACT Expansion and Persistence
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Solution Overview
Problem
Current Adoptive Cell Therapy (ACT) treatments for diseases such as cancer face challenges with suboptimal T cell function, expansion, and persistence.
Innovation Solution
An epigenetic-modifying DNA-targeting system comprising fusion proteins with DNA-binding domains and transcriptional repressor or activator effector domains to target specific genes in T cells, enhancing or repressing their transcription.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Reliability
If current ACT treatments are used, then T cell therapy can be administered, but T cell function, expansion, and persistence are suboptimal
Solution Approach 1:
The patent modifies T cell function by changing the expression levels of specific genes through epigenetic editing. By targeting genes like CBLB, CD5, and KDM1A for repression or activation, the system alters molecular parameters within T cells to enhance their functional properties, including proliferation and persistence capabilities
Solution Approach 2:
The patent performs preliminary genetic modifications to T cells before they are administered to patients. By pre-editing the T cells to optimize their gene expression profiles, the system prepares them in advance to achieve better expansion and persistence outcomes once introduced into the patient's body
2Reliability
If epigenetic-modifying DNA-targeting system is used, then T cell effector functions are enhanced, but system complexity increases
Solution Approach 1:
The epigenetic-modifying system is divided into discrete functional modules: a DNA-binding domain (such as CRISPR-Cas or zinc finger proteins) that targets specific genomic locations, and effector domains (such as transcriptional activators or repressors) that modify gene expression. This modular segmentation allows for targeted manipulation of specific genes while keeping the overall system manageable and programmable
Data Source
AI summary
Provided are epigenetic-modifying DNA-targeting systems, such as CRISPR-Cas/guide RNA (gRNA) systems, that bind to or target a target site in a gene or regulatory element thereof in a T cell. In some aspects, the provided epigenetic modifying DNA-targeting systems modulate a T cell function, such as a T cell phenotype or activity. In some aspects, also provided herein are methods and uses related to the provided compositions, for example in modulating T cells including in connection with methods of adoptive T cell therapy.