For the first time ever, scientists at UCSF have started using Regulatory T cells (Tregs) to treat onset type 1 diabetes (T1D) in humans. Jeffrey Bluestone, the scientist heading this revolutionary therapy, had this to say, “For T1D, we’ve traditionally given immunosuppressive drugs, but this trial gives us a new way forward. By using Tregs to ‘re-educate’ the immune system, we may be able to really change the course of this disease.”
Diabetes is an increasing problem in America, with 10% of the population diagnosed. There are two forms of the condition, T1D accounts for 5-10% of total diabetics. T1D is an autoimmune disease that is caused by immune cells attacking insulin producing beta cells. Over time a deluge from white blood cells (WBCs) exterminate the beta cells resulting in T1D. There is no cure for diabetes, but recent studies have implicated the clinical importance of Tregs in T1D.
Of the WBCs in the body that attack insulin producing beta cells, helper T cells play a major role in the extinction insulin secreting cells. However, there are subsets of T cells, one of which, Tregs, exhibit highly immunosuppressive properties when stimulated. Tregs, when stimulated, are able to halt the destruction of beta cells and restore homeostasis in the body. Numerous studies have concluded that increasing the number of Tregs can prevent or halt the progression of autoimmune diseases like T1D in mice. Recent findings of defective Treg populations in patients with T1D provides new insights into the nature of the T1D.
Tregs in patients with T1D have an activation defect that results in fewer numbers of activated Tregs and greater numbers of resting Tregs. As a result, there are too few activated Tregs that are able to suppress the immune response. Over time, the inflammatory immune cells extinguish the insulin producing cells, giving rise to T1D. Jeffrey Bluestone’s novel therapeutic idea is to isolate Tregs from a patient’s blood, expand the activated Tregs in a lab and infuse them back into the patient.
Mary Rooney, a trial patient diagnosed with T1D 4 years prior to treatment, experienced no side effects from the Treg intervention. “The work of Dr. Bluestone and his team offers new hope for people with type 1 diabetes and other autoimmune disorders,” Rooney said. “The Treg intervention aims to prevent the development and progression of type 1 diabetes, freeing people like me from the daily grind of insulin therapy and lifelong fear of complications. It’s truly groundbreaking research with enormous potential.”
Bluestone and his team withdraw a few cups of blood from a patient and then isolate Tregs. This typically yields 2 to 4 million cells. The cells are then expanded until they attain a 1500 fold increase in number. After the expansion, the cells are infused into the patient. This study consisted of 14 members in four groups, each group receiving a different dose of Tregs ranging from 5 million to 2.6 billion. In all four groups the transfusion of Tregs was well tolerated. The next clinical trial is now recruiting patients. To be eligible, you would have to be over 18 and have been diagnosed within 2 years according to the American Diabetes Association standard criteria.
“Using a patient’s own cells – identifying them, isolating them, expanding them, and infusing them back into the patient – is an exciting new pillar for drug development.”
-Jeffrey Bluestone, PhD
In the context of autoimmune diseases, the addition of Tregs to suppress the immune system is a great idea. Although the intent of this clinical trial was to measure the safeness of administration of Tregs, the results “support the development of a Phase 2 trial to test efficacy of the Treg therapy,” However, numerous studies have confirmed that Tregs surround tumors in patients diagnosed with cancer. Scientists cleverly took advantage of the inflammatory function of helper T cells to annihilate cancer.
Cover picture credit: WebMD