Trial Tests Safety of Promising Therapy for Patients With Type 1 Diabetes

Many current treatments for type 1 diabetes (T1D) have been designed with the aim of suppressing immune response to prevent a person’s immune system from attacking his or her own insulin-secreting beta cells in the pancreas. However, at the same time, these treatments can leave the body vulnerable to infection or cancer.

A recent safety trial led by UC San Francisco (UCSF) researchers has found a promising new therapy that uses patients’ own regulatory T-cells (Tregs) instead of the usual immunosuppressive drugs to protect beta cells. In the body, Tregs naturally suppress immune responses of other cells while holding potential autoimmune over-responses in check. In other words, the use of Tregs in the UCSF trial was justified based on the concept of “immune tolerance”—as reported in Science Translational Medicine—“these cells may have the capability to dampen the immune system’s assault on beta cells while leaving its infection-fighting capabilities intact.”

The UCSF trial included 14 patients between 18 and 43 years of age with recent-onset T1D. They were organized into 4 groups, which received different volumes of Treg infusions—the lowest being 5 million cells and the greatest being 2.6 billion. To collect the Tregs, doctors removed around 2 cups of blood from each patient and isolated the Tregs from the rest of the blood components before placing them in a growth medium. The Tregs were augmented in number by almost 1500 times and then infused back into their trial participant.

A subset of the transferred Tregs was long-lived, with up to 25% of the peak level still remaining in the patient’s blood 1 year after transfer. Immune studies also showed increases in Treg level and broad retention of Treg types in recipients. No patient from any of the groups experienced any serious side effects.

Even though the trial tested safety results instead of efficacy, these results are still a promising first step towards a complete therapy and, as the trial’s research team wrote, support the development of a Phase 2 trial to test efficacy.

“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,” primary report author Jeffrey Bluestone, PhD, said. “This could be a game-changer. For type 1 diabetes, 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.”

Bluestone also discussed the potential value of Treg therapy to be expanded into use as treatment for other immune diseases such as rheumatoid arthritis and lupus, and even cardiovascular and neurological diseases in the future.