This New Therapy Can Treat Type 1 Diabetes By Restoring Insulin-Producing Pancreatic Cells: Study​

Genetically engineered T cells can be used to treat type 1 diabetes by restoring insulin-producing pancreatic cells.

An international team of researchers has successfully treated type 1 diabetes in mice using pancreatic beta-cell, target-specific, chimeric antigen-receptor (CAR) regulatory T cells. Pancreatic beta cells are endocrine cells which synthesise, store, and release insulin. Chimeric antigen-receptor T cells are the T cells which have been genetically engineered to produce T cell receptors for use in immunotherapy. These cells are used for the treatment of certain kinds of blood cancers. 

The team of researchers has demonstrated the feasibility of this approach to treat type 1 diabetes, according to data presented on Monday, June 13, at ENDO 2022, the annual meeting of the Endocrine Society in Atlanta, Georgia. The Endocrine Society is a medical organisation in the field of endocrinology and metabolism. 

The study was led by Juan Carlos Jaume, Director of the Center for Diabetes and Endocrine Research (CeDER), at the University of Toledo in Toledo, Ohio.

What Are Adoptive Cell Transfer Therapies And How Can They Be Used To Treat Type 1 Diabetes?

Adoptive cell transfer therapies with chimeric antigen-receptor regulatory T cells have been found to be effective for the treatment of haematological malignancies.  Adoptive cell transfer is the transfer of cells into a patient, which may have originated from the patient or from another individual. Chimeric antigen receptor regulatory T cells are antigen-specific immunosuppressive cells that help prevent undesired immune responses. Engineered T cell receptors called chimeric antigen receptors allow direct recognition of a target antigen without requiring antigen presentation. This is a process in the body's immune system by which different cells capture antigens, and then present them to naive T cells, which enable the body to fight off new, unrecognised infections and diseases. Haematologic malignancies are cancers that begin in blood-forming tissue such as bone marrow, or in the cells of the immune system. These cancers can be treated with the help of adoptive cell transfer therapies. 

How Can Genetically Engineered T Cells Cure Type 1 Diabetes?

The researchers attempted to replicate an equally effective experimental treatment for type 1 diabetes using non-cytotoxic, anti-inflammatory regulatory T-cells. Regulatory T cells are T cells which have a role in regulating or suppressing other cells in the immune system, and help prevent autoimmune disease. Non-cytotoxic regulatory T cells do not directly kill other cells. 

According to a statement released by the Endocrine Society, the researchers drew blood one to two weeks prior to pancreatic surgery. The pancreas was removed for a clinically indicated reason such as cancer or pancreatitis. After this, they collected a small piece of the pancreas. 

The researchers isolated regulatory T cells from the blood samples and expanded them in vitro. They genetically modified the cells to express a beta-cell, target-specific chimeric antigen-receptor combined with a green fluorescence protein (GFP) marker. 

Then, the researchers processed the pancreas tissue for islet separation. Islets of Langerhans are a group of pancreatic cells which secrete insulin.

The researchers co-cultured the human pancreatic islets combined with the beta-cell, target-specific chimeric antigen-receptor regulatory T cells. 

It was observed that within 24 hours, the GFP positive, chimeric antigen-receptor regulatory T cells successfully migrated onto the pancreatic islets. The chimeric antigen-receptor regulatory T cells significantly proliferated when they were in physical contact with the pancreatic islets in the subsequent 72 hours.

In the statement, Jaume said that the study is the first successful, pancreatic beta-cell, target specific chimeric antigen-receptor-regulatory T cell treatment of type 1 diabetes in a humanised mouse model which closely resembles the human disease. He added that based on their mice and human in-vitro data, the researchers believe treatment with these cells will for recovery and reconstitution of beta cells in human type 1 diabetes patients as well.

The immune system of a person with type 1 diabetes attacks and destroys the cells in the pancreas that make insulin, as a result of which the organ stops making the hormone. The genetically engineered beta cell, target-specific T cells can prevent undesired immune responses, thereby serving as a treatment for type 1 diabetes. Thus, the therapy helps restore the pancreatic beta cells.