UCSF Pediatric Focus

Immunotherapy Shows Promise for Type 1 Diabetes Treatment

A phase II study tests a novel immunotherapy that uses patients’ own immune cells to protect cells that produce insulin.

A multicenter phase II study for adolescents between the ages of 12 and 17 is testing whether immunomodulatory therapy can halt destruction of beta cells and preserve naturally occurring insulin production in adolescents recently diagnosed with type 1 diabetes (T1D).

The hope of this study, which is led by UCSF’s Stephen Gitelman, MD, is that by isolating and expanding a patient’s own specific regulatory T cells, or Tregs, the therapy could help alter the course of T1D and ease the burden for those with the disease. In the future, this approach might also be used to prevent the development of T1D and to block further autoimmune destruction of beta cells for those with long-standing T1D who are being treated with stem cell-derived beta cell replacement therapy.

Proven Safe

Last year, in the first safety trial of this immunotherapy conducted in the United States, Gitelman co-led a study with UCSF’s Jeffrey Bluestone, PhD, that showed evidence of safety and tolerability of autologous Treg cell therapy in study participants receiving infusions of as many as 2.6 billion Tregs. Published in Science Translational Medicine, the study did not formally assess effectiveness, but many of the participants had no decline in beta cell function during the two years of observation after their one-time infusion.

Those results led to the current study, called T-Rex, which will test whether Tregs can effectively re-educate the immune system and protect pancreatic beta cells. In the study, researchers will isolate and purify each participant’s Tregs from his or her own blood sample, expand the Tregs approximately a thousandfold and reinfuse the cells back into the same patient.

UCSF is the lead center, and the study aims to enroll more than 100 patients across multiple sites. Gitelman expects to finish enrollment within the next year. Researchers will follow the subjects for two years, and analysis will begin after all subjects have reached the one-year mark.

Potential to Enhance Prevention and Treatment in Many Autoimmune Disorders

“Those of us who research therapeutic options for type 1 diabetes see three options to alter the natural course of disease: prevention in those at risk, preservation for those with recent-onset disease, and replacement for those with long-standing disease and no residual beta cell function remaining,” says Gitelman.

Identifying those at risk and developing preventive therapies for T1D is ideal; the international consortium TrialNet is pioneering this process. Failing prevention, those with a recent diagnosis of T1D may have between 15 percent and 40 percent of their beta cells remaining. In such cases, patients still need supplemental insulin, but in general, those with more of their own beta cell insulin have better clinical outcomes. Finally, if patients do not have functional beta cells remaining, it is now possible to make replacement beta cells from stem cells. In all three of those scenarios, Tregs’ potential to protect beta cells from destruction can be a true breakthrough for T1D.

Bluestone originally developed the strategy in preclinical models at UCSF, and Gitelman says, “This is a great example of how a local discovery [in a UCSF research lab] can make it to the bedside for assessment of clinical use. T1D is the initial clinical indication being explored, but there are early studies underway in other autoimmune conditions, including lupus and uveitis, as well as in organ transplantation.”