Insulin-producing cell reconstitution therapy coming soon?

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Type 1 diabetes is an autoimmune disease that affects the lives of approximately 40 million people worldwide. The immune system attacks the pancreas, preventing it from producing insulin, the hormone that normally regulates blood sugar levels. Although effective, the therapeutic use of regulatory (reg) T cells to treat autoimmune diseases has been limited by the scarcity of antigen-specific T-regs. Recently, researchers successfully treated type 1 diabetes in mice using pancreatic beta cells, antigen receptors and specific T-reg cells. They demonstrated the feasibility of their approach to treating the disease in humans at the annual meeting of theendocrine society at Atlanta on 13.

Type 1 diabetes (T1D) is an autoimmune disease that results from the destruction of the beta cells of the islets of Langerhans in the pancreas by the immune system itself and specifically by autoreactive T lymphocytes.

Promising research from the University of Toledo, still in the experimental stage, suggests that type 1 diabetes could be cured by reprogramming the patient’s own immune cells to heal the pancreas and the body’s ability to produce insulin to restore. Instead of taking insulin every day, the disease could therefore be treated with an infusion of immune cells, says Dr. Juan Jaume, endocrinologist, professor of medicine and director of the Center for Diabetes Research and UToledo-Endocrinology, who led the project.

CAR-T cell therapy: replenish insulin-producing beta cells

His approach is based on CAR-T cell therapy (combination of gene therapy and cell therapy), which is already known from the possible treatment of certain types of blood cancer such as leukemia. CARs refer to chimeric antigen receptors and T-Reg cells are lymphocytes that can inhibit a dysregulated immune response. In this case, the regulatory CAR-T cells should stop and not overload a specific immune response against a target.

The purpose of this study was to determine whether human pancreatic beta cell-specific CAR T-regs also identify human pancreatic beta cells (target) and localize in culture in human pancreatic islets (where beta cells live) implantation, as they do in mice given CAR-T-Reg treatment for T1D Jaume said in a statement.

The researchers used a humanized mouse model that expressed diabetes similar to humans. They did a blood test one to two weeks before pancreatic surgery, then a removal of a small piece of pancreas after removal of the pancreas for a clinically indicated reason (cancer or pancreatitis).

First, T cells were taken from the blood and then genetically modified in vitro to express a beta cell-specific CAR associated with a green fluorescent protein (GFP) marker. The pancreatic islets were then co-cultivated with the CAR-T-regs for 7 days. Result: Microscopy showed successful migration of CAR-T regs GFP to pancreatic islets in just 24 hours. In addition, CAR-T-regs increased significantly when in physical contact with pancreatic islets over the following 72 hours.

These regulatory immune cells would thus make it possible to regulate the immune response and restore the insulin-producing target cells in the pancreas. ” Our study is the first to successfully treat T1D with specific pancreatic beta-cell CAR T-regs in a humanized mouse model closely resembling the human disease. » says Jaume. ” Based on our in vitro data in mice and humans, we believe that treatment with pancreatic beta cell-specific CAR T-regs will enable beta cell recovery and reconstitution in human patients with T1D. “.

Source: University of Toledo

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