Immunotherapy could be the next major advance in diabetes treatment.

Multiple types of pathogenic T cells have been implicated in the beta cell destruction that underlies type 1 diabetes and some type 2 diabetes, and engineered T regulatory (Treg) cells can protect beta cells.

“Type 1 is an autoimmune disease, and autoimmune diseases like rheumatoid arthritis and type 1 diabetes are largely mediated by T cells,” explained Kathryn Haskins, PhD, Professor of Immunology and Microbiology at the University of Colorado School of Medicine. “People have been using autoantibodies as predictors of diabetes, but autoantibodies don’t necessarily reflect an ongoing disease process. If we could find pathogenic T cells that are involved in active disease, we might be able to look at therapeutic interventions.”

Dr. Haskins is one of four researchers who will discuss the latest findings in this area during the Scientific Sessions symposium T Cells in Diabetes—Past, Present, and Future, which will be held from 2:15 – 4:15 p.m. ET Monday, June 28. She will discuss efforts to induce tolerance to a hybrid insulin peptide that activates cluster of differentiation 4 (CD4) T cells to attack and destroy beta cells.

Lucy S.K. Walker, PhD, Professor of Immune Regulation, University College, London, United Kingdom, will review the role of follicular T (Tfh) cells in type 1 diabetes. Differences in Tfh profiles may predict response to abatacept, used widely to treat rheumatoid arthritis and other autoimmune diseases.

“Targeting T cells is probably going to be one of the chief ways in which we treat and delay diabetes,” Dr. Haskins said. “There have been some interesting results in inducing tolerance in humans, tamping down the inflammatory CD4 cells that are attacking beta cells. We have early results with an islet transplant animal model inducing tolerance for improved graft survival, and there are other approaches, like using Tregs.”

Improved animal models have helped fuel many recent T cell advances. The familiar nonobese diabetic (NOD) mouse does not share major histocompatibility complexes (MHCs) with humans. Improved NOD mice that express some human MHC molecules have helped.

“You can never make a human mouse, but we are modeling certain aspects that are important in T cell work,” said Teresa P. DiLorenzo, PhD, Professor of Microbiology & Immunology and Medicine, and the Diane Belfer, Cypres & Endelson Families Faculty Scholar in Diabetes Research at Albert Einstein College of Medicine. “And targeting T cells is working. A proof-of-principle study tamping down CD3 (cluster of differentiation 3) cells with teplizumab delayed the onset of type 1 diabetes by about two years and has helped to rejuvenate interest in T cells and T regulatory cells.”

A central concern in any autoimmune disease is maintaining the necessary immunogenic protective activities of T cells while suppressing autoimmune responses. Tregs are immunoprotective.

“We all have T cells with the ability to attack our beta cells and produce diabetes, but they’re normally kept under control by regulatory T cells,” explained Megan K. Levings, PhD, Professor of Surgery and Biomedical Engineering at the University of British Columbia and Lead of Childhood Diseases Research at BC Children’s Hospital Research Institute, Vancouver, Canada. “If we could find a way to boost Tregs, we would have a new tool to help keep the pathogenic T cells under control.”

Enter chimeric antigen receptor (CAR) T cell therapy. In cancer, CAR T cells are genetically engineered to find and attack cancer cells. Dr. Levings is using a similar approach to engineer Tregs to better control pathogenic T cells.

“There is amazing progress in cell therapy for cancer. These advances are now feeding back into the autoimmune space,” Dr. Levings said.