UF diabetes researchers test therapy to prevent immune attack against insulin-producing cells

GAINESVILLE, Fla. — It is, in a sense, like visiting the scene of an intended crime.

A new University of Florida Health study details a new strategy to potentially slow the progression of Type 1 diabetes using a drug designed to act directly on insulin-producing cells in the pancreas.

That is where the body’s immune system mistakenly attacks and destroys those cells.

Once there, the drug — a complex molecule designed by the British biotechnology company Immunocore Holdings plc — shuts down the immune system’s T cells that would otherwise destroy the cells responsible for producing insulin in the pancreas.

In a study published in Science Advances on Wednesday, the experimental therapy showed promising effectiveness.

“The beauty of this drug is that it is tailored and targeted at the beta cells that produce insulin,” said biomedical engineer Edward A. Phelps, Ph.D., a member of the UF Diabetes Institute and senior study author. “It basically prevents the loss of insulin secretion.”

Phelps is an associate professor in the UF Herbert Wertheim College of Engineering’s J. Crayton Pruitt Family Department of Biomedical Engineering.

Any drug approval would be years distant, with much more research required. Immunocore is planning a Phase I clinical trial in Europe to evaluate the safety and benefit of the drug. UF is not a participant in that trial.

Efforts to slow Type 1 diabetes have largely relied on broad immune suppression. While that approach can reduce damage, it can also interfere with normal immune function.

The new strategy is more precise. The molecule developed by Immunocore, a protein called ImmTAAI, homes in on beta cells and acts only at the site of the immune attack.

The molecule has a two-part structure, Phelps said. One part directs the drug to beta cells by recognizing insulin fragments on their surfaces. The other delivers a signal that tells nearby immune cells to stand down.

“What that does is it interfaces with immune cells … and gives them an off signal,” Phelps said. “It inhibits them.”

T cells patrol the body, checking cells for signs of infection or disease. When they recognize a problem, such as a virus-infected or cancerous cell, they bind to it and release substances that trigger that cell’s destruction.

In attacking the cells that make insulin, however, the engineered molecule sends a signal to the T cells that tells them, “Don’t stop here, keep moving, go away,” Phelps said.

Researchers tested the molecule in thin slices of fresh human pancreas tissue obtained from organ donors. These slices retain the structure and function of live tissue. That gives scientists a better idea of how the therapy might work in humans.

The samples came from the UF-based Network for Pancreatic Organ donors with Diabetes, or nPOD, the world’s largest repository of such tissue.

Scientists then mimicked Type 1 diabetes by adding T cells engineered to attack insulin-producing cells. Without treatment, the experiments showed, insulin production dropped by more than half, Phelps said. When the experimental drug was added, however, insulin secretion remained at normal levels.

The findings come with important limitations. The experiments were conducted in lab-grown systems and human tissue samples, not in patients. Researchers also note that the therapy may need to be repeated to maintain effectiveness.

“This is a basic science study,” Phelps said. “We can’t really predict yet how it’s going to perform in the disease, but that’s what the clinical trial is going to tell us.”

The study’s lead author is Matthew W. Becker, Ph.D., a former doctoral student in Phelps’ lab now affiliated with Arizona State University.