Insulin-Supported T Cell Engineering for Viability and Expansion
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Solution Overview
Problem
Existing genetic engineering methods face challenges in improving the viability and expansion capacity of genetically engineered T cells, particularly in the context of T cell-based therapies for cancer and immune system regulation.
Innovation Solution
The method involves contacting T cells with a gene editing reagent and culturing them in the presence of insulin, an insulin analog, or an insulin agonist before, during, or after gene editing to enhance cell viability and efficiency, and monitoring mitochondrial function and cell metabolism.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Reliability
If conventional gene editing methods are used to engineer T cells, then genetic modification can be achieved, but cell viability and expansion capacity are reduced
Solution Approach 1:
The patent applies preliminary action by treating T cells with insulin or insulin analogs before gene editing procedures. This pre-treatment enhances cell metabolic state and prepares cells for better survival and expansion during and after genetic modification, directly addressing the viability and expansion capacity problems
Solution Approach 2:
The patent changes the biochemical parameters of the culture system by introducing insulin or insulin analogs at specific concentrations and time points. This parameter modification alters cell metabolic pathways to improve both viability and expansion capacity during gene editing processes
2Ease of manufacture
If gene editing reagents are introduced to T cells, then genetic engineering can be performed, but cell stress and mortality increase
Solution Approach 1:
The patent implements beforehand cushioning by pre-treating T cells with insulin or insulin analogs before introducing gene editing reagents. This creates a protective metabolic state that cushions cells against the stress of genetic modification, reducing mortality while maintaining editing efficiency
Solution Approach 2:
Insulin or insulin analogs serve as intermediary substances that mediate between the gene editing reagents and T cells. The insulin treatment creates a favorable metabolic environment that facilitates successful gene editing while protecting cells from reagent-induced damage
Data Source
AI summary
Provided herein, inter alia, are methods and compositions for engineering T cells. The methods include culturing a T cell with insulin during engineering of the T cell. The methods provided herein are contemplated to increase cell viability, expansion and gene editing efficiency, thereby allowing an increase in the total number of engineered T cells.