Objective
To compare the function and stability of engineered regulatory T cells generated using our novel, patented method with natural regulatory T cells in a cell culture model of suppression of islet cell killing by autoreactive T cells.
Background Rationale
Type 1 diabetes is caused by the destruction of insulin-producing cells in the pancreas by the population of immune cells called "conventional T cells". In healthy individuals, these cells are controlled by other immune cells called "regulatory T cells", and there is intense interest in finding ways to use regulatory T cells in therapy for type 1 diabetes. However, major challenges exist with using the regulatory T cells from a type 1 diabetes patient for their own therapy. A potential solution is to engineer regulatory T cells, allowing for the creation of a larger number of regulatory T cells with greater functionality and stability. Although the advantages of engineered regulatory T cells are clear, it is not clear how to engineer effective regulatory T cells for clinical use. We have developed a novel, patented method to engineer regulatory T cells from conventional T cells. Our goal is to determine if these engineered regulatory T cells can be used as therapy in type 1 diabetes treatment.
Description of Project
Type 1 diabetes is caused by the destruction of insulin-producing cells in the pancreas by the population of immune cells called "conventional T cells". In healthy individuals, these cells are controlled by other immune cells called "regulatory T cells", and there is intense interest in finding ways to use regulatory T cells in therapy for type 1 diabetes. However, major challenges exist with using the regulatory T cells from a type 1 diabetes patient for their own therapy. A potential solution is to engineer regulatory T cells, allowing for the creation of a larger number of regulatory T cells with greater functionality and stability. Although the advantages of engineered regulatory T cells are clear, it is not clear how to engineer effective regulatory T cells for clinical use. We have developed a novel, patented method to engineer regulatory T cells from conventional T cells. Our goal is to determine if these engineered regulatory T cells can be used as therapy in type 1 diabetes treatment. We will determine the ability of these engineered regulatory T cells generated from conventional T cells isolated from peripheral blood to inhibit islet cell killing by conventional T cells in a cell culture model. We will compare the function of these engineered regulatory T cells with natural regulatory T cells isolated from peripheral blood. If these studies are successful, this would be a significant step forward towards developing a large pool of stable regulatory T cells for type 1 diabetes therapy.
Anticipated Outcome
We will have determined the immunosuppressive function, mechanism, and stability of a novel population of engineered regulatory T cells and compared them with the activity of natural regulatory T cells against islet-killing T cells in a cell culture model. These studies are a critical first step to determine if this novel method for engineering regulatory T cells can potentially be used in type 1 diabetes therapy.
Relevance to T1D
If these studies are successful, this would be a significant step forward towards developing a large pool of stable Tregs for T1D therapy.