Regulatory T cells 're-educate' the immune system to treat type 1 diabetes

Regulatory T cells are defective in type 1 diabetes (T1D) and other autoimmune diseases. Now a phase 1 clinical trial has demonstrated an immunotherapy treatment in which healthy regulatory T cells (Tregs) can be multiplied by the thousands and reintroduced back into T1D patients.

The research, published online November 25, 2015 in the journal Science Translational Medicine, holds the promise of a long-lasting and less burdensome treatment for people with type 1 diabetes (T1D).

“This could be a game-changer,” said first author Jeffrey A. Bluestone, PhD, the AW and Mary Margaret Clausen Distinguished Professor in Metabolism and Endocrinology at the University of California San Francisco, CA. “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.”

In this study, investigators drew 400 ml of blood from each of 14 adults with recent-onset T1D. From each sample, researchers segregated 2 to 4 million therapeutic Tregs and placed these into a growth medium in which they increased up to 1,500-fold. The researchers organized patients into four groups that successively received infusions containing greater numbers of Tregs: members in the first group received about 5 million cells, while those in the fourth group received about 2.6 billion cells.

In previous research, Dr. Bluestone’s team showed that this process produces Tregs that are more functionally active, can repair defects in the immune system of patients with T1D, and are more likely to survive long-term in the body than Tregs produced by other means.

This is the first U.S. study in which large populations of Tregs created by this technique were infused back into patients’ circulation. The treatment was well tolerated by all four patient groups and also long-lasting—up to 25% of the infused therapeutic cells were still detectable in patients’ circulation a year after a single infusion.

“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,” Dr. Bluestone said, “and we expect Tregs to be an important part of diabetes therapy in the future.”

Based on the results of this study, Caladrius Pharmaceuticals is now in the early stages of planning a phase 2 trial to determine whether this therapy can restore immunologic tolerance and prevent T1D progression.